UpToDate
UpToDate خرید پکیج
تعداد آیتم قابل مشاهده باقیمانده: 4

Selective IgA deficiency

Selective IgA deficiency
Author:
Robert W Hostoffer, DO, LhD, MSMed, MBA, FACOP, FAAP, FACOI, FCCP
Section Editor:
Jordan S Orange, MD, PhD
Deputy Editor:
Anna M Feldweg, MD
Literature review current through: May 2025. | This topic last updated: May 22, 2025.

INTRODUCTION — 

Selective immunoglobulin A (IgA) deficiency (sIgAD) is believed to be the most common inborn error of immunity (IEI; also known as primary immunodeficiencies) in the human population. The clinical manifestations of sIgAD are variable, ranging from no symptoms to recurrent infections, atopy, autoimmune disease, and malignancy. This topic will review the epidemiology, clinical manifestations, diagnosis, pathophysiology, management, and prognosis of this disorder. The structure and normal functions of IgA are reviewed separately. (See "Structure and biologic functions of IgA".)

DEFINITION — 

sIgAD (MIM 137100) may be defined as undetectable serum IgA levels (less than 7 mg/dL [0.07 g/L] when measured at least twice) in the setting of normal serum levels of immunoglobulin G (IgG) and immunoglobulin M (IgM) in an individual older than four years of age in whom other causes of hypogammaglobulinemia have been excluded [1-3].

Additional features of sIgAD differ slightly in American and European practice parameters, as follows:

●The 2015 American practice parameter for the diagnosis and management of primary immunodeficiency further notes that sIgAD is characterized by normal levels of IgG subclasses and normal or impaired IgG responses to polysaccharide antigens [4].

Of note, low but detectable levels of IgA, previously referred to as partial IgA deficiency, are no longer considered to be an IEI, because there are no clinical disorders that are consistently associated with IgA levels in this range in the absence of other immunologic abnormalities [5]. This finding can be referred to as having a low IgA without conferring any disease state [2,6].

This practice parameter also defines a related disorder in which undetectable IgA is accompanied by a deficiency in one or more IgG subclasses (with normal total IgG), called IgA deficiency with IgG subclass deficiency [4]. Responses to polysaccharide antigens are impaired.

●The European Society for Immunodeficiencies (ESID; 2019 update) differs from the American practice parameter in specifying that IgG responses to vaccines are normal and T cell defects should be excluded [3].

In this topic review, the definition of the 2015 American practice parameter for the diagnosis and management of primary immunodeficiency will be used [4]. In the future, there will hopefully be closer alignment between the two groups' definitions.

EPIDEMIOLOGY — 

sIgAD is the most common immunologic defect in humans [7,8]. It is considered to be a primary humoral immunodeficiency, even though most affected individuals are asymptomatic. Estimates of prevalence are typically obtained through studies of healthy blood donors. Prevalence ranges from 1 in 100 to 1 in 1000 in much of the world [9-21]. Of note, because the definition of the disorder has evolved over time, earlier studies likely overestimated the prevalence because low levels of IgA were previously included in the definition. The condition may be less common in Asian populations, with reported prevalence rates ranging from 1 in 1615 to 1 in 20,000 in different regions of China and Japan [22-25].

Risk factors — The most significant risk factor for having IgAD is a family history of either IgAD or the more profound defect in antibody function, common variable immunodeficiency (CVID). First-degree relatives of affected individuals are 50 times more likely to be affected themselves compared with unaffected people. Affected mothers are more likely than affected fathers to transmit the disorder to their offspring [26,27]. In the Swedish population, a higher frequency of IgAD was found more commonly in monozygotic twins (1 in 241) and dizygotic twins (1 in 198) as compared with the normal population (1 in 600) [28]. However, the exact pattern of inheritance of IgAD remains unclear [29].

PATHOPHYSIOLOGY — 

sIgAD is believed to be a heterogeneous disorder that probably arises through several pathogenic mechanisms. The precise molecular defects are unknown. However, most humoral immunodeficiencies arise from either defects in B cells or defective interactions between B and T cells. A brief review of normal B cell development and antibody production is helpful in understanding the theories of pathogenesis.

Normal biology of IgA — IgA accounts for more than 70 percent of total immunoglobulin in the body. The normal functions of IgA are mentioned briefly here and discussed in detail separately. (See "Structure and biologic functions of IgA".)

IgA exists in two distinct forms:

●Monomeric IgA in the serum – This type of IgA interacts with the phagocytic arm of the immune system. IgA molecules bind foreign antigens through their Fab portions, while the Fc portion binds to the Fc-alpha receptor (CD89) located on the cell surface of neutrophils, eosinophils, and macrophages [6,30]. IgA binding to the receptor initiates ingestion and destruction of the microorganism by the phagocyte. (See "Overview of therapeutic monoclonal antibodies".)

●Dimeric secretory IgA in secretions – This form of IgA is found in saliva, milk, colostrum, tears, and mucosal secretions from the respiratory tract, genitourinary tract, and prostate. It is called secretory IgA and is believed to be important in mucosal immunity. Its actions include coating of microbes to prevent adherence to epithelial cells and neutralization of microbial toxins, as well as dampening of inflammatory pathways that could lead to autoimmune processes. In addition, secretory IgA promotes intestinal homeostasis between the host and commensal bacteria by regulating bacterial communities, favoring commensal organisms in biofilms, and preventing pathogen overgrowth.

Abnormalities in sIgAD — The pathophysiology of sIgAD is not fully understood, although abnormalities in B cells and T regulatory cells have been demonstrated, and several genetic variants are associated with the condition.

●B cell abnormalities – In patients with sIgAD, B cells expressing surface IgA are present but appear to be developmentally blocked. Theoretically, the defect resides after the surface coexpression of IgM and IgA, although this has not been established with certainty. Based on animal studies, the failure of B cells to terminally differentiate into plasma cells that secrete IgA may be due to the lack of effects from various cytokines, such as interleukin (IL) 21, IL-4, IL-6, IL-7, or IL-10, although other mechanisms have also been proposed [31-38]. B cells found in IgA-deficient patients show a decrease in the frequency of switched memory B cells, transitional cells, and plasmablasts, as well as an increase in CD21low CD38low subset [39].

●T regulatory cells – The mean percentage of T regulatory cells (CD4+, CD25high, FoxP3+ T cells) was significantly lower in 26 children (ages 4 to 17 years) with sIgAD compared with normal controls [40]. When patients with sIgAD were classified into two groups based on the percentages of T regulatory cells, a greater proportion of those with lower T regulatory cells had autoimmune disorders, pneumonia, and evidence of class-switching defects. Additionally, in other studies, the gene signature of T regulatory cells is different in IgA-deficient patients with autoimmune disorders as compared with control populations, showing enrichments in innate immune responses [41].

●Genetic factors – IgAD is associated with several types of genetic abnormalities and associations [42], although none are known to be causative, and there may be other, more relevant defects that have not been identified.

•Associated molecular defects – The first genetic defect to be identified in patients with sIgAD was a mutation in the tumor necrosis factor (TNF) receptor family member "transmembrane activator and calcium-modulator and cyclophilin ligand interactor" (TACI), a molecule that mediates isotype-switching in B cells. However, TACI mutations/polymorphisms have been identified in only a small subset of patients with sIgAD, as well as in some patients with common variable immunodeficiency (CVID), and it is not clear that these mutations/polymorphisms are directly related to pathogenesis [43]. B cells in these patients expressed TACI but did not produce IgG and IgA in response to the TACI ligand, suggesting impaired isotype switching [44,45]. (See "Pathogenesis of common variable immunodeficiency".)

•Large chromosomal abnormalities – There are conflicting findings concerning the presence or absence of large chromosomal abnormalities. Some studies have reported abnormalities involving chromosomes 16 and 18, while other studies have not found consistent abnormalities within IgA-deficient families [29,46-53]. Long- or short-arm deletion and ring formation have been described in some patients who are also intellectually disabled and exhibit additional dysmorphic features [50]. These findings are probably not relevant to asymptomatic IgA-deficient patients.

•Major histocompatibility complex (MHC) loci associations – Associations have also been identified between sIgAD and several genes of the MHC [53-61]. Defects in MSH5, a gene encoded in the central MHC class III region, are also associated with IgAD and CVID [62].

•Abnormalities in genes associated with autoimmunity – Genome-wide association studies revealed an association between sIgAD and genetic variants in the genes for interferon-induced helicase C domain-containing protein (IFIH1) and for C-type lectin domain family 16 (CLEC16A) [63]. Mutations in these loci are also associated with autoimmune disorders [60,64]. In a European genome-wide association study, four loci in a rare IFIH1 variant were found in patients with sIgAD and may lead to the conclusion that sIgAD may be due to a complex network of gene effects. These loci also overlapped with autoimmune markers [65]. These findings draw a loose connection between sIgAD and an autoimmune diathesis, although further studies are necessary to show causality.

Possible compensatory mechanisms — Despite the apparent importance of IgA in mucosal immunity, the vast majority of patients with IgAD do not experience more frequent or severe infections or overt autoimmune disease. This disconnect between the presumed role of IgA and clinical observations of IgAD is probably explained by the presence of redundant immunologic mechanisms that protect the host. For example, secretory IgM may perform many of the same functions and may compensate for lack of IgA in normal neonates and in patients with IgAD [66,67]. Consistent with this, most IgA-deficient patients (although not all [68]) appear to have increased production of secretory IgM [69-71], and IgA and IgM have evolutionary, structural, and functional similarities [72-74].

CLINICAL MANIFESTATIONS IN SYMPTOMATIC PATIENTS

Most individuals are asymptomatic — More than one-half of individuals with sIgAD are believed to be asymptomatic [75]. Less than one-third come to medical attention and usually for the following types of disorders [76-78]:

●Recurrent infections (most commonly sinopulmonary and gastrointestinal)

●Allergic disorders

●Autoimmune disorders

In a meta-analysis of 40 studies from 39 countries, the prevalence of respiratory infections, allergic disorders, and autoimmunity was 51, 29, and 22 percent, respectively [5]. As with other immune disorders, lymphomas and gastrointestinal malignancies have been reported, but it has not been established that patients with sIgAD are at increased risk for neoplastic disease [79].

Serum levels of IgA in deficient patients do not necessarily correlate with the occurrence or severity of these disorders, and the pathophysiologic relationship between the deficiency of IgA and the disorders listed above has not been clearly delineated. (See 'Pathophysiology' above.)

Recurrent infections — Some patients with sIgAD suffer from recurrent infections, most often affecting the sinopulmonary tract [5]. Gastrointestinal infections are seen to a lesser degree. Sinopulmonary infections may be more common than gastrointestinal infections in sIgAD because secreted IgM, which may partially compensate for the deficiency of IgA, is more prominent in the gut than the respiratory tract [80].

Sinopulmonary — Children with sIgAD may experience recurrent otitis media, sinusitis, and/or pneumonia. Adults with sIgAD may also suffer from recurrent sinusitis and pulmonary infections, while otitis media is less common [10,71,81]. These infections are most commonly caused by encapsulated bacteria (eg, Streptococcus pneumoniae, Haemophilus influenzae). There have been several reports of patients presenting with end-organ damage, such as bronchiectasis, due to chronic and recurrent infections [82,83]. A meta-analysis of studies describing the clinical manifestations of sIgAD suggested that the pooled prevalence of bronchiectasis in patients with IgAD was 15 percent [5].

Common viral respiratory tract infections (colds), laryngitis, and infectious conjunctivitis are also more common in patients with sIgAD compared with age- and sex-matched controls in some studies [10,84].

It can be difficult to know what constitutes an excessive number of sinopulmonary infections, although immunologic societies have estimated that four or more newer infections, two or more serious sinus infections, or two or more episodes of pneumonia within a single year is concerning for the presence of an inborn error of immunity (IEI) [85-87]. However, not all patients with this number of infections will be found to have an immune defect. An individual's susceptibility to these common infections can vary tremendously from year to year, depending on multiple factors, such as exposure to children (for adults), variations in the incidence and virulence of common respiratory viruses, stress levels, and other transient fluctuations in health status. (See "Approach to the child with recurrent infections" and "Approach to the adult with recurrent infections".)

Gastrointestinal — In a meta-analysis of studies of sIgAD patients, gastrointestinal infections were present in 16 percent [5]. Some IgA-deficient patients suffer from gastrointestinal infections due to Giardia lamblia [88-91]. (See "Giardiasis: Epidemiology, clinical manifestations, and diagnosis".)

In contrast, individuals with IgAD appear to have adequate defenses against other types of gastrointestinal infections. As an example, patients were shown to clear rotavirus infections normally and generate higher levels of total IgG and IgG1 subclass antibodies compared with normal controls [92].

Gastrointestinal disorders (noninfectious) — Celiac disease and inflammatory bowel disease occur with increased prevalence in patients with sIgAD [60,64,93]. (See "Epidemiology, pathogenesis, and clinical manifestations of celiac disease in adults" and "Gastrointestinal manifestations in inborn errors of immunity".)

Celiac disease — Celiac disease is reported in approximately 6 to 7 percent of patients with sIgAD [5,60,64,94]. Patients with celiac disease may present with classic symptoms related to malabsorption, including diarrhea, steatorrhea, weight loss, and nutrient or vitamin deficiencies. However, many patients with celiac disease exhibit only minor gastrointestinal complaints, have nongastrointestinal manifestations, or are asymptomatic. When screening for celiac disease in patients with sIgAD, IgG-antigliadin antibodies or an IgG test for tissue transglutaminase is preferable to IgA-based assays, as the latter may be falsely negative [95]. (See "Diagnosis of celiac disease in adults", section on 'Negative serology'.)

Inflammatory bowel disease — Inflammatory bowel diseases, including ulcerative colitis and Crohn disease, are associated with sIgAD, although the pathophysiologic relationship is unclear [96-99]. A meta-analysis of clinical manifestations of patients with IgAD suggested that the prevalence of inflammatory bowel disease was approximately 4 percent [5].

●In children and adolescents, inflammatory bowel diseases should be considered in those presenting with loose stools or bloody diarrhea, abdominal pain, weight loss or growth failure, perianal disease, anemia, arthritis, or delayed onset of puberty. (See "Clinical presentation and diagnosis of inflammatory bowel disease in children".)

●Adults with ulcerative colitis usually present with diarrhea that is associated with blood. Accompanying symptoms include colicky abdominal pain, urgency, and tenesmus. Patients may also have fever, fatigue, and weight loss. Ulcerative colitis primarily involves the intestine but may be associated with several extraintestinal manifestations. (See "Clinical manifestations, diagnosis, and prognosis of ulcerative colitis in adults".)

●Adults with Crohn disease usually present with persistent diarrhea accompanied by abdominal pain with or without gross bleeding, fatigue, and weight loss. Symptoms may be present for years before the diagnosis is made. (See "Clinical manifestations, diagnosis, and prognosis of Crohn disease in adults".)

Nodular lymphoid hyperplasia — Nodular lymphoid hyperplasia, also known as follicular lymphoid hyperplasia, is a benign finding in the small intestine that is associated with sIgAD, common variable immunodeficiency (CVID), and gastrointestinal lymphoma (picture 1) [100-103]. It is discussed separately. (See "Clinical presentation and diagnosis of primary gastrointestinal lymphomas", section on 'Predisposing conditions'.)

Allergic diseases and asthma — The meta-analysis of clinical manifestations in patients with IgAD found prevalences of asthma, allergic rhinitis, and allergic conjunctivitis of 19, 15, and 12 percent, respectively [5].

Anaphylactic reactions to blood products — Rare anaphylactic reactions to blood products have been reported in patients with sIgAD, as well as in those with CVID [104-114]. These reactions have been theorized to be due to the presence of antibodies directed against IgA, which can form in a minority of patients with undetectable levels of serum IgA. Reactions occur when anti-IgA antibodies react to small amounts of IgA in plasma or immune globulin products. However, there are several other reasons for anaphylactic reactions to blood products, which are reviewed separately. (See "Immunologic transfusion reactions", section on 'Anaphylactic transfusion reactions'.)

Considerations in patients with sIgAD who have experienced allergic symptoms upon receiving blood products are discussed below. (See 'Patients who reacted to a blood product' below.)

Autoimmune disorders and autoantibodies — Among patients followed in immunology clinics, approximately 20 to 30 percent of patients with sIgAD develop autoimmune disorders [10,60,64,115,116]. Similarly, a meta-analysis of clinical manifestations in patients with IgAD suggested that the prevalence autoimmunity was 22 percent [5].

In particular, systemic lupus erythematosus (SLE), Graves' disease, type 1 diabetes, vitiligo, both juvenile- and adult-onset rheumatoid arthritis, and immune thrombocytopenia are associated with sIgAD [60,64,95,117-128]. Myasthenia gravis may also be associated, although data are conflicting.

Individuals with sIgAD have an increased prevalence of autoantibodies without symptoms of overt autoimmune disease [115,129-133]. In one series comparing 60 sIgAD patients with a normal control population, 90 percent had detectable autoantibodies, and 40 percent had six or more autoantibodies [129].

False-positive pregnancy tests have been reported in IgA-deficient females, a phenomenon that has been attributed to the presence of heterophile antibodies [134]. Heterophile antibodies are discussed separately. (See "Infectious mononucleosis".)

Autoimmunity is seen in several types of humoral immunodeficiencies, including sIgAD and CVID. Theories about the relationship between autoimmunity and IgAD include the following:

●The immune system is normally prevented from damaging self-tissues by the elimination (or negative selection) of cells that strongly react against self-antigens. These mechanisms are believed to be compromised in some humoral immunodeficiencies. (See "Normal B and T lymphocyte development" and "Primary humoral immunodeficiencies: An overview".)

●An alternative theory is that individuals with IgAD have underlying genetic factors that independently predispose to autoimmunity, without there being a direct causal relationship between the IgAD and autoimmune disease. The observation that the prevalence of autoimmune disorders is increased among first-degree relatives of patients with IgAD supports this theory [60,64,135].

●A third theory posits that the compromised mucosal barrier in sIgAD allows for abnormal passage of food antigens through the gut wall. In some patients, this may lead to the formation of autoreactive antibodies and autoimmune disease due to molecular mimicry between large food proteins, such as milk, and host antigens. One study showed that the presence of antibodies against milk in patients with IgAD correlated with an increased frequency of serum autoantibodies [136].

ASSOCIATED DISORDERS

Other inborn errors of immunity — IgAD is associated with several inborn errors of immunity (IEI) [137]:

●IgG2 subclass deficiency – Deficiency in IgG2 has been described, both associated with IgAD and as an isolated finding. (See "IgG subclass deficiency", section on 'IgG2 deficiency'.)

●Common variable immunodeficiency (CVID) – Some cases of sIgAD may progress to CVID. There is genetic variation of both the transmembrane activator and calcium modulator and cyclophilin-ligand interactor (TACI) and MutS homolog 4/5 (MSH4/5) in both patients with IgAD and CVID [45,62,138-143]. In addition, families have been described in which affected individuals progress from a normal immunologic state to IgAD with and without IgG subclass deficiency or CVID [29,46,144]. The propensity to progress to CVID may be stronger in familial and major histocompatibility complex (MHC) associated sIgAD or in patients with 18q deletion syndrome [141,145]. In these cases, genetic testing may assist in defining specific humoral deficiencies. (See "Pathogenesis of common variable immunodeficiency", section on 'Genetics'.)

●Ataxia-telangiectasia – This is a disorder that presents in early childhood with progressive cerebellar ataxia, abnormal eye movements, other neurologic abnormalities, oculocutaneous telangiectasias, and immunodeficiency. (See "Ataxia-telangiectasia".)

●DiGeorge syndrome – This presents with conotruncal cardiac anomalies, hypoplastic thymus, and hypocalcemia, often in the setting of developmental delay and frequent infections. (See "DiGeorge (22q11.2 deletion) syndrome: Clinical features and diagnosis".)

●Recombination-activating gene (RAG) 1 and 2 deficiency – This is a form of severe combined immunodeficiency (SCID) involving a defect in lymphocyte gene rearrangement [146]. (See "T-B-NK+ SCID: Pathogenesis, clinical manifestations, and diagnosis", section on 'RAG complex (initiation of recombination)'.)

Malignancies — Individuals with sIgAD have been found to have a moderately increased risk of cancer, particularly involving the gastrointestinal tract. The risk appears more significant in adults than children [147,148]. A meta-analysis of the clinical manifestations in patients with IgAD suggested that the prevalence of malignancy in patients with IgAD was 3.7 percent [5].

Other — In one large study, there was an increased prevalence of neurologic disorders such as epilepsy, autism spectrum disorders, and tics in patients with sIgAD compared with a matched control patient population, suggesting a cause-and-effect relationship between these neurologic disorders and sIgAD [149]. These findings require further confirmation.

WHEN TO REFER — 

Patients with low or undetectable levels of IgA that are detected incidentally do not necessarily require additional immunologic evaluation if they are entirely asymptomatic. However, patients with recurrent infections, gastrointestinal disorders, or evidence of autoimmunity should be referred to a clinical immunologist.

EVALUATION AND DIAGNOSIS

Indications for evaluation — An evaluation for sIgAD is appropriate in the following patients:

●A child with recurrent otitis media, sinusitis, and/or pneumonia

●An adult with recurrent/chronic sinusitis or pulmonary infections

●A patient of any age with one or more of the following:

•Absence or low level of IgA on routine immunoglobulin examination

•Celiac disease

•Gastrointestinal infection with Giardia lamblia

•Unexplained and recurrent autoimmune phenomena

•A family history of IgAD or common variable immunodeficiency (CVID)

•A past anaphylactic reaction to blood products

Initial laboratory evaluation — The initial evaluation should include the measurement of serum concentrations of IgA, IgG, and IgM. A repeat level of IgA should be done to confirm the initial test. In sIgAD, only IgA is low. Serum levels of IgG and IgM must be normal. In contrast, patients with CVID have low levels of IgG plus low levels of IgA, IgM, or both.

Diagnosis — The diagnosis of sIgAD requires an undetectable level of serum IgA (less than 7 mg/dL [0.07 g/L] when measured at least twice) in the presence of normal IgG and IgM levels in a patient older than four years of age in whom other causes of hypogammaglobulinemia have been excluded [3].

Considerations in young children — The evaluation of any serum immunoglobulins in young children is best undertaken after the age of six months since maternal immunoglobulins (particularly IgG) are present until this age, although maternal IgA does not cross the placental barrier to a significant degree under normal circumstances. For this reason, children with antibody defects do not generally present with recurrent infections until after six months, when maternal antibodies have been cleared and the child's underlying deficiency is unmasked.

In children younger than four years, the diagnosis should be considered preliminary, and the child should be monitored over time to see if IgA levels normalize. IgA levels may normalize as late as adolescence [150].

Observations about the natural history of sIgAD are reviewed separately. (See 'Prognosis' below.)

Functional testing of the patient's humoral immune response using vaccine challenge is not part of the diagnostic criteria for sIgAD in the American definition, although it is part of the evaluation found in the European Society for Immunodeficiencies (ESID) definition, but this can be reconciled if indicated due to recurrent sinopulmonary infections, as discussed below [4]. (See 'Patients with recurrent infections' below.)

Further evaluation — Further evaluation depends on the patient's clinical presentation. This may include a complete blood count (CBC) with differential, chemistry panel, screening tests for autoimmunity (antinuclear antibodies and thyroid autoantibodies), and screening tests for chronic infection or inflammation (erythrocyte sedimentation rate [ESR] and/or a C-reactive protein [CRP]). A total serum immunoglobulin E (IgE) is also appropriate as a screen for allergic disease.

The measurement of IgA in specific bodily fluids is considered a research tool and is not recommended, since IgA levels in secretions are highly variable. Patients with measurable serum IgA levels have sufficient secretory IgA, and patients with low serum IgA levels (<7 mg/dL) can be assumed to have little or no secretory IgA. There is also no need to measure IgA isotypes (IgA1 and IgA2).

Patients with recurrent infections — Sinus imaging and chest radiography should be considered if there is a history of lower or upper respiratory infection.

In addition to serum levels of IgA, IgG, and IgM, a CBC with differential and total hemolytic complement (THC or CH50) assay should be obtained to screen for other immunologic causes of recurrent infections. If the serum IgG level is normal, then IgG subclasses should be measured, as IgG2 subclass deficiency may coexist with IgAD (which is designated IgAD with IgG subclass deficiency) [151]. (See "Laboratory evaluation of the immune system" and "IgG subclass deficiency".)

Patients with undetectable sIgAD may have impaired IgG responses to protein and polysaccharide antigens, although antibody function is not part of the diagnostic criteria in the 2015 American practice parameter [4]. Still, assessment of vaccine responses is clinically useful because, if it is impaired, then the cause of the patient's recurrent infections has been identified, and immune globulin replacement therapy is sometimes indicated. The evaluation may then progress to B cell phenotyping or immune genetic evaluation to define other humoral deficiencies.

In addition, patients with impaired antibody function should be monitored for evolution to CVID. (See 'Prognosis' below.)

DIFFERENTIAL DIAGNOSIS — 

The differential diagnosis of sIgAD includes other inborn errors of immunity (IEI) and secondary IgAD due to medications.

Other inborn errors of immunity — IgA deficiency may be detected in a patient with another, more severe immunodeficiency, as discussed previously. (See 'Other inborn errors of immunity' above.)

Two of the more common disorders that could be mistaken for sIgAD are:

●Transient hypogammaglobulinemia of infancy (THI) – THI may be defined as a prolongation of the "physiologic" hypogammaglobulinemia of infancy, which is normally observed during the first three to six months of life. Vaccine responses are normal in children with THI. The diagnostic criteria for THI vary somewhat worldwide. Most definitions require that IgG be reduced, with or without reductions in other immunoglobulin classes, but some criteria accept an isolated low IgA level as sufficient for the diagnosis. Because of the changing nature of immunoglobulin levels in young children, THI is an appropriate diagnosis for children under four years of age with low immunoglobulin levels, whereas the diagnosis of sIgAD is best deferred until the child is older than four. (See "Transient hypogammaglobulinemia of infancy".)

●Evolving common variable immunodeficiency (CVID) and other humoral immunodeficiencies – Patients with sIgAD who developed CVID over time have been reported [139]. Therefore, patients who continue to suffer from repeated infections and develop conditions associated with CVID, such as autoimmune hemolytic anemia or thrombocytopenia, should have IgG levels and vaccine responses assessed periodically. The diagnosis of CVID requires low IgG and low IgA or low IgM, in conjunction with impaired vaccine response. In these cases, B cell phenotyping or immune genetic testing may elucidate the humoral etiology that is responsible for the deficit. (See 'Associated disorders' above and "Clinical manifestations, epidemiology, and diagnosis of common variable immunodeficiency in adults".)

Drug-induced immunoglobulin disorders — Several medications can cause low levels of IgA, usually in combination with reductions in serum levels of other immunoglobulin classes. Most of these are reversible with discontinuation of the responsible medication, although cyclosporine A has been reported to cause permanent IgAD even after the drug has been stopped [152].

Examples of drugs that may cause reversible reductions in serum IgA levels include the following:

●Antiseizure medications [153], including phenytoin [154-157], valproic acid [121], lamotrigine [158], carbamazepine [159], and zonisamide [160]

●D-penicillamine [161-163]

●Captopril [164,165]

●Sulfasalazine [166]

●Fenclofenac [167]

●Gold [168]

●Thyroxine [169]

●Cyclosporine [152]

MANAGEMENT

Monitoring asymptomatic patients — There is no consensus about how asymptomatic patients should be monitored. The approach of the author and editors of UpToDate is to ask patients to return at periodic intervals to review the frequency of infections, as well as a thorough review of systems. We also suggest checking levels of IgA, IgG, and IgM periodically.

Interventions for all patients — All individuals with sIgAD should be informed about the associated conditions but also reassured that the majority of people with this laboratory finding are healthy and live normal lives. (See 'Information for patients' below.)

Performing serum immunoglobulin levels at intervals on patients with sIgAD may be useful if respiratory tract infections become prominent.

Vaccinations — For asymptomatic individuals with IgAD, there are no special restrictions for vaccine administration once the diagnosis of sIgAD is confirmed [170]. A possible exception is the patient in whom the diagnosis of sIgAD is preliminary because an immune evaluation is incomplete. In such patients, a more cautious approach is warranted, and live local vaccines (eg, intranasal influenza and live rotavirus) should also be avoided until the evaluation is complete. These additional restrictions are warranted because IgAD can be a finding in other, more severe immunodeficiencies (eg, ataxia-telangiectasia), which preclude a wider array of live vaccines.

Certain vaccines, such as the pneumococcal and Haemophilus influenzae type b vaccine, are specifically recommended for patients with sIgAD to help reduce the risk of sinopulmonary infections [171].

Patients with frequent infections

●Prevention of sinopulmonary infections – The most common clinical manifestation of symptomatic sIgAD is recurrent sinopulmonary infections or recurrent otitis media in younger children, which may impact the patient's full participation in life (school, job, social functioning). Patients may benefit from several interventions to prevent or reduce the frequency of these illnesses, such as treatment of concomitant rhinitis or asthma, and/or prophylactic antibiotics.

Any contributing conditions, such as chronic rhinosinusitis, allergic rhinitis/asthma, or chronic nonallergic rhinitis, should be actively sought and managed, as these conditions could be the primary driver of recurrent infection [4]. (See "Chronic rhinosinusitis: Clinical manifestations, pathophysiology, and diagnosis" and "Pharmacotherapy of allergic rhinitis" and "An overview of asthma management in children and adults" and "Chronic nonallergic rhinitis".)

●Prophylactic antibiotics – For patients with continued infections despite management of underlying conditions, a limited trial of daily prophylactic antibiotics can be instituted to determine if infections are prevented. Maintenance prophylactic antibiotics may be continued if the initial course is successful. It may also be possible to administer these antibiotics only during the winter, depending upon the patient's historic pattern of infections. Note that the use of immune globulin, which contains very little IgA, is not recommended [172].

We are aware of no studies specifically evaluating the efficacy of prophylactic antibiotics in patients with sIgAD and recurrent sinopulmonary infections. Use is based on expert opinion and extrapolation from studies of patients with other mild antibody deficiencies, such as IgG subclass deficiency or specific antibody deficiency [173]. Azithromycin, amoxicillin, or trimethoprim-sulfamethoxazole are appropriate for the prevention of sinopulmonary infections [174].

•Azithromycin:

-Children – 5 mg/kg (max 250 mg) three times per week.

-Adults – 250 or 500 mg three times per week.

Note that caution is warranted in adult patients using CYP3A inhibitors and other medications or conditions that can prolong the QT interval along with macrolides (table 1): Cardiac side effects associated with prolonged repolarization resulting in QT prolongation may increase the risk of sudden death. (See "Azithromycin and clarithromycin", section on 'QT interval prolongation and cardiovascular events'.)

Some experts also advocate screening for mycobacterial infection in patients at increased risk for latent infection and in areas that are endemic for mycobacterial exposure due to the high risk of resistance development with monotherapy.

•Amoxicillin:

-Children – 125 to 250 mg/5 mL based on weight, daily.

-Adults - 250 mg daily.

•Trimethoprim-sulfamethoxazole:

-Children - 5 mg/kg daily.

-Adults - 160 mg daily.

●Giardia infection – Patients with sIgAD can become infected with Giardia lamblia from contaminated private wells, public sources, and bottled water. The clinical manifestations and diagnosis of acute and chronic infection are reviewed separately. (See "Giardiasis: Epidemiology, clinical manifestations, and diagnosis".)

Measures to reduce Giardia exposure through drinking water are discussed separately. (See "Giardiasis: Treatment and prevention", section on 'Counseling and prevention'.)

●COVID-19 – It is unclear whether sIgAD patients experience a more severe illness course with infection of coronavirus disease 2019 (COVID-19). One small study looking at 11 patients with sIgAD and COVID-19 infection showed a 7.7-fold higher risk of severe disease compared with controls [175]. In another larger cohort of 772 patients with sIgAD with matched controls who were observed over 34 months, sIgAD was associated with higher rates of COVID-19 infection and reinfection [176]. Other studies suggest that sIgAD is an underrecognized risk for severe COVID-19 infections [177]. This may have been due to a diminished mucosal IgA presence, although larger studies are necessary [178].

Patients who reacted to a blood product — Patients with sIgAD can experience infusion reactions to blood products containing small amounts of IgA, typically in plasma, including the following:

●Whole blood

●Red blood cells

●Platelets

●Fresh frozen plasma

●Cryoprecipitate

●Granulocytes

●Intravenous immune globulin (although immune globulin contains very low amounts of IgA compared with other products above)

Anti-IgA antibodies have been identified in severely IgA-deficient patients who experienced infusion reactions to blood products and have been implicated as the cause of these infusion reactions, although it has not been conclusively demonstrated that these antibodies cause the reactions [179]. Anti-IgA antibodies are usually only found in patients with undetectable serum IgA, and, even among such individuals, antibodies to IgA are rare. In studies of blood donors, anti-IgA antibodies were detected in severely IgA-deficient patients at a frequency of approximately 1 in 1200 to 1600 [18,180]. Indirect evidence in support of the role of anti-IgA antibodies includes the finding that these antibodies are more prevalent in patients with sIgAD who have experienced anaphylaxis compared with those who have not [180].

There are two types of anti-IgA antibodies, which are IgG and IgE, and both may be implicated in adverse reactions to blood products [104,179,181,182]. IgE anti-IgA is much less common than IgG anti-IgA. IgE anti-IgA was demonstrated in only 1 individual in a series of 46 IgA-deficient patients, and this individual had life-threatening anaphylaxis in response to intravenous immune globulin [107]. Despite these uncertainties, the diagnosis of IgA-related anaphylaxis is usually assumed if a patient experiences infusion-related anaphylaxis and has undetectable serum IgA combined with anti-IgA antibodies of either type.

Commercial assays for the detection of anti-IgA antibodies are available, although there have been periodic disruptions in reagent supply [183-185]. These may be IgG or IgE immunoassays, and a positive test for the IgG isotype assumes that the patient might also be capable of producing IgE against IgA. Percutaneous skin testing with potentially infused blood products in patients with IgAD may be utilized, although intradermal testing may be more revealing [186].

Whom to evaluate for anti-IgA antibodies — We suggest evaluating for anti-IgA antibodies in all patients with sIgAD and in patients with partial sIgAD who have experienced an infusion reaction to a blood product in the past. Screening for anti-IgA antibodies allows clinicians to identify patients at risk for infusion reactions and helps these patients become informed about the potential risks of receiving blood products.

Preparation for future treatment — Patients with sIgAD who have reacted to a blood product, either with or without positive testing for anti-IgA antibodies (as patients with negative screens can become sensitized over time), are advised to obtain a medical alert bracelet/necklace inscribed with the following information:

●The patient has sIgAD.

●The patient is at risk for an allergic reaction to any injected plasma-containing blood products, and testing for anti-IgA antibodies should be performed before such blood products are administered.

All blood products should be used with caution in IgA-deficient patients, and appropriate staff and medication should be available to treat anaphylaxis [114]. For patients who have already experienced an infusion reaction to plasma-containing blood products, a strategy should be devised for safe administration of future blood products. The approach will differ depending on the blood product needed. Consultation with a transfusion medicine specialist should be considered [187]. Examples include the following:

●Patients who require transfusions of red blood cells can receive cells that have been washed to remove as much of the contaminating IgA as possible. In addition, some hospitals reserve a list of patients with sIgAD who would be willing to donate blood for transfusion for those patients with sIgAD [188-190]. (See "Immunologic transfusion reactions".)

●Desensitization to blood products is another approach that may be appropriate in specific circumstances. A case report described desensitization of a patient with sIgAD who experienced anaphylaxis to blood products but subsequently required numerous infusions of various blood products in the context of liver transplant. The patient was successfully desensitized to an immune globulin preparation, which was then administered weekly to maintain the desensitized state [191].

Patients with specific conditions — The management of allergic or autoimmune disorders in patients with sIgAD is identical to management in patients without IgAD and is discussed in related topic reviews.

PROGNOSIS — 

Information about the prognosis of sIgAD is limited, and it is not known if the severity of sIgAD (ie, serum IgA levels) impacts prognosis. Available studies have found the following:

●sIgAD in children usually persists [192-195]. In a large study of 184 children followed for a mean of 8.9 years, IgA levels increased or normalized in 9 and 4 percent, respectively [195]. Three patients progressed to CVID at a mean age of 15 years.

●sIgAD can uncommonly progress to common variable immunodeficiency (CVID) [138-143,195,196]. This tended to occur in adolescence or young adulthood in the available case reports. (See 'Pathophysiology' above.)

●The prognosis of IgAD diagnosed in adulthood is not well studied, and it is not known if the condition spontaneously remits in a subset of individuals. Ultimately, prognosis probably depends largely upon the presence and severity of associated disorders or progression of the immunodeficiency. A Latin American registry of inborn errors of immunity (IEI) that included 1627 patients with sIgAD reported just one death due to the condition (0.06 percent mortality).

SOCIETY GUIDELINE LINKS — 

Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Inborn errors of immunity (previously called primary immunodeficiencies)".)

INFORMATION FOR PATIENTS — 

UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topic (See "Patient education: IgA deficiency (The Basics)".)

SUMMARY AND RECOMMENDATIONS

●Definition – Selective immunoglobulin A deficiency (sIgAD; MIM 137100) may be defined as the selective deficiency of serum IgA (ie, serum levels of immunoglobulin G [IgG] and immunoglobulin M [IgM] are normal) in a patient older than four years of age, in whom other causes of hypogammaglobulinemia have been excluded. A serum IgA level <7 mg/dL (or 0.07 g/L) is considered a deficiency. Those patients with an IgA >7 mg/dL but less than the normal range per age may be referred to as having a low IgA or, more descriptively, by using the actual concentration numbers without conferring any disease state and not having sIgAD. (See 'Definition' above.)

●sIgAD is common – sIgAD is considered the most common immunodeficiency in humans, with prevalence ranges from 1 in 100 to 1 in 1000 in White, Black, and Middle Eastern populations. It is less common in Asian populations. (See 'Epidemiology' above.)

●Pathophysiology – sIgAD is believed to be a heterogeneous disorder that probably arises through several pathogenic mechanisms. The precise molecular defects are unknown. However, most humoral immunodeficiencies arise from either defects in B cells or defective interactions between B and T cells. IgA is concentrated in mucosal secretions and is believed to be important in the immune functioning of the mucosal barrier. However, patients with sIgAD sometimes have increased production of secretory IgM, which may partly compensate for the lack of IgA. (See 'Pathophysiology' above.)

●Clinical manifestations and associated disorders – More than one-half of individuals with sIgAD are believed to be asymptomatic. Less than one-third come to medical attention and usually for recurrent sinopulmonary and gastrointestinal infections, allergic disorders, or autoimmune disorders. Rare anaphylactic transfusion reactions to plasma-containing blood products can occur in patients with sIgAD, possibly due to anti-IgA antibodies. Other inborn errors of immunity (IEI) and some malignancies are associated with sIgAD. (See 'Clinical manifestations in symptomatic patients' above and 'Associated disorders' above.)

●Evaluation and diagnosis – All patients should have serum levels of IgA, IgG, and IgM measured. Serum levels of IgG and IgM levels must be normal to consider the diagnosis of sIgAD. A serum IgA level <7 mg/dL, measured at least twice, is considered a deficiency. Further evaluation depends upon the patient's clinical presentation. In patients who are asymptomatic and have no disorders associated with sIgAD, no further evaluation is indicated. (See 'Evaluation and diagnosis' above.)

●Referral – patients with recurrent infections, gastrointestinal disorders, or evidence of autoimmunity should be referred to a clinical immunologist. (See 'When to refer' above.)

●Differential diagnosis – Other disorders in which serum IgA may be low include several other immune disorders and secondary IgAD due to medications. (See 'Differential diagnosis' above.)

●Management of sinopulmonary infections – Patients with recurrent sinopulmonary symptoms should be evaluated and treated for other conditions predisposing to upper respiratory tract infections (eg, allergic rhinitis/asthma, chronic rhinosinusitis). In addition, certain vaccines, such as the pneumococcal and Haemophilus influenzae type b vaccine, may help reduce the risk of sinopulmonary infections. In patients who continue to have sinopulmonary infections despite these measures, we suggest a trial of prophylactic antibiotics (Grade 2C). (See 'Patients with frequent infections' above.)

●Prognosis – sIgAD is believed to persist in most patients and may rarely progress to common variable immunodeficiency (CVID). The prognosis of patients with sIgAD probably depends largely upon the presence and severity of associated disorders. (See 'Prognosis' above.)

  1. Tangye SG, Al-Herz W, Bousfiha A, et al. Human Inborn Errors of Immunity: 2022 Update on the Classification from the International Union of Immunological Societies Expert Committee. J Clin Immunol 2022; 42:1473.
  2. Yel L. Selective IgA deficiency. J Clin Immunol 2010; 30:10.
  3. Seidel MG, Kindle G, Gathmann B, et al. The European Society for Immunodeficiencies (ESID) Registry Working Definitions for the Clinical Diagnosis of Inborn Errors of Immunity. J Allergy Clin Immunol Pract 2019; 7:1763.
  4. Bonilla FA, Khan DA, Ballas ZK, et al. Practice parameter for the diagnosis and management of primary immunodeficiency. J Allergy Clin Immunol 2015; 136:1186.
  5. Vosughimotlagh A, Rasouli SE, Rafiemanesh H, et al. Clinical manifestation for immunoglobulin A deficiency: a systematic review and meta-analysis. Allergy Asthma Clin Immunol 2023; 19:75.
  6. Hostoffer RW, Krukovets I, Berger M. Increased Fc alpha R expression and IgA-mediated function on neutrophils induced by chemoattractants. J Immunol 1993; 150:4532.
  7. Vo Ngoc DT, Krist L, van Overveld FJ, Rijkers GT. The long and winding road to IgA deficiency: causes and consequences. Expert Rev Clin Immunol 2017; 13:371.
  8. Stiehm ER. The four most common pediatric immunodeficiencies. J Immunotoxicol 2008; 5:227.
  9. al-Attas RA, Rahi AH. Primary antibody deficiency in Arabs: first report from eastern Saudi Arabia. J Clin Immunol 1998; 18:368.
  10. Morawska I, Kurkowska S, Bębnowska D, et al. The Epidemiology and Clinical Presentations of Atopic Diseases in Selective IgA Deficiency. J Clin Med 2021; 10.
  11. Pereira LF, Sapiña AM, Arroyo J, et al. Prevalence of selective IgA deficiency in Spain: more than we thought. Blood 1997; 90:893.
  12. Ezeoke AC. Selective IgA deficiency (SIgAD) in Eastern Nigeria. Afr J Med Med Sci 1988; 17:17.
  13. Litzman J, Sevcíková I, Stikarovská D, et al. IgA deficiency in Czech healthy individuals and selected patient groups. Int Arch Allergy Immunol 2000; 123:177.
  14. Gudmundsson S, Jensson O. Frequency of IgA deficiency in blood donors and Rh negative women in Iceland. Acta Pathol Microbiol Scand C 1977; 85:87.
  15. Saghafi S, Pourpak Z, Aghamohammadi A, et al. Selective immunoglobulin A deficiency in Iranian blood donors: prevalence, laboratory and clinical findings. Iran J Allergy Asthma Immunol 2008; 7:157.
  16. Holt PD, Tandy NP, Anstee DJ. Screening of blood donors for IgA deficiency: a study of the donor population of south-west England. J Clin Pathol 1977; 30:1007.
  17. Carneiro-Sampaio MM, Carbonare SB, Rozentraub RB, et al. Frequency of selective IgA deficiency among Brazilian blood donors and healthy pregnant women. Allergol Immunopathol (Madr) 1989; 17:213.
  18. Palmer DS, O'Toole J, Montreuil T, et al. Screening of Canadian Blood Services donors for severe immunoglobulin A deficiency. Transfusion 2010; 50:1524.
  19. Giza S, Kotanidou E, Papadopoulou-Alataki E, et al. Prevalence of selective immunoglobulin A deficiency in Greek children and adolescents with type 1 diabetes. World J Pediatr 2016; 12:470.
  20. Urbonas V, Sadauskaite J, Cerkauskiene R, et al. Population-Based Screening for Selective Immunoglobulin A (IgA) Deficiency in Lithuanian Children Using a Rapid Antibody-Based Fingertip Test. Med Sci Monit 2016; 22:4773.
  21. Lu P, Ling B, Wang N, Hammarstrom L. [Study on immunoglobulin A Deficiency(IgAD) in Chinese Shanghai Blood Donors]. Zhongguo Shi Yan Xue Ye Xue Za Zhi 2016; 24:1216.
  22. Zhang J, Kong W, Ni J, et al. The epidemiology and clinical feature of selective immunoglobulin a deficiency of Zhejiang Province in China. J Clin Lab Anal 2020; 34:e23440.
  23. Feng ML, Zhao YL, Shen T, et al. Prevalence of immunoglobulin A deficiency in Chinese blood donors and evaluation of anaphylactic transfusion reaction risk. Transfus Med 2011; 21:338.
  24. Feng L. [Epidemiological study of selective IgA deficiency among 6 nationalities in China]. Zhonghua Yi Xue Za Zhi 1992; 72:88.
  25. Kanoh T, Mizumoto T, Yasuda N, et al. Selective IgA deficiency in Japanese blood donors: frequency and statistical analysis. Vox Sang 1986; 50:81.
  26. Vorechovský I, Webster AD, Plebani A, Hammarström L. Genetic linkage of IgA deficiency to the major histocompatibility complex: evidence for allele segregation distortion, parent-of-origin penetrance differences, and the role of anti-IgA antibodies in disease predisposition. Am J Hum Genet 1999; 64:1096.
  27. Vorechovský I, Zetterquist H, Paganelli R, et al. Family and linkage study of selective IgA deficiency and common variable immunodeficiency. Clin Immunol Immunopathol 1995; 77:185.
  28. Frankowiack M, Kovanen RM, Repasky GA, et al. The higher frequency of IgA deficiency among Swedish twins is not explained by HLA haplotypes. Genes Immun 2015; 16:199.
  29. Koistinen J. Familial clustering of selective IgA deficiency. Vox Sang 1976; 30:181.
  30. Monteiro RC, Hostoffer RW, Cooper MD, et al. Definition of immunoglobulin A receptors on eosinophils and their enhanced expression in allergic individuals. J Clin Invest 1993; 92:1681.
  31. Bagheri Y, Saeidi M, Yazdani R, et al. Evaluation of effective factors on IL-10 signaling in B cells in patients with selective IgA deficiency. Eur Cytokine Netw 2022; 33:1.
  32. Borte S, Pan-Hammarström Q, Liu C, et al. Interleukin-21 restores immunoglobulin production ex vivo in patients with common variable immunodeficiency and selective IgA deficiency. Blood 2009; 114:4089.
  33. Husain Z, Holodick N, Day C, et al. Increased apoptosis of CD20+ IgA + B cells is the basis for IgA deficiency: the molecular mechanism for correction in vitro by IL-10 and CD40L. J Clin Immunol 2006; 26:113.
  34. Ramsay AJ, Husband AJ, Ramshaw IA, et al. The role of interleukin-6 in mucosal IgA antibody responses in vivo. Science 1994; 264:561.
  35. Okahashi N, Yamamoto M, Vancott JL, et al. Oral immunization of interleukin-4 (IL-4) knockout mice with a recombinant Salmonella strain or cholera toxin reveals that CD4+ Th2 cells producing IL-6 and IL-10 are associated with mucosal immunoglobulin A responses. Infect Immun 1996; 64:1516.
  36. Snapper CM, Zelazowski P, Rosas FR, et al. B cells from p50/NF-kappa B knockout mice have selective defects in proliferation, differentiation, germ-line CH transcription, and Ig class switching. J Immunol 1996; 156:183.
  37. Brière F, Chevet D, Bridon JM, et al. [B lymphocytes of patients with complete IgA deficiency secrete IgA in response to interleukin 10]. Nephrologie 1996; 17:289.
  38. Kowalczyk D, Mytar B, Zembala M. Cytokine production in transient hypogammaglobulinemia and isolated IgA deficiency. J Allergy Clin Immunol 1997; 100:556.
  39. Nechvatalova J, Pikulova Z, Stikarovska D, et al. B-lymphocyte subpopulations in patients with selective IgA deficiency. J Clin Immunol 2012; 32:441.
  40. Soheili H, Abolhassani H, Arandi N, et al. Evaluation of natural regulatory T cells in subjects with selective IgA deficiency: from senior idea to novel opportunities. Int Arch Allergy Immunol 2013; 160:208.
  41. Rutkowska-Zapała M, Grabowska-Gurgul A, Lenart M, et al. Gene Signature of Regulatory T Cells Isolated from Children with Selective IgA Deficiency and Common Variable Immunodeficiency. Cells 2024; 13.
  42. Willis TW, Gkrania-Klotsas E, Wareham NJ, et al. Leveraging pleiotropy identifies common-variant associations with selective IgA deficiency. Clin Immunol 2024; 268:110356.
  43. Pan-Hammarström Q, Salzer U, Du L, et al. Reexamining the role of TACI coding variants in common variable immunodeficiency and selective IgA deficiency. Nat Genet 2007; 39:429.
  44. Castigli E, Wilson SA, Garibyan L, et al. TACI is mutant in common variable immunodeficiency and IgA deficiency. Nat Genet 2005; 37:829.
  45. Rachid R, Castigli E, Geha RS, Bonilla FA. TACI mutation in common variable immunodeficiency and IgA deficiency. Curr Allergy Asthma Rep 2006; 6:357.
  46. Vassallo CL, Zawadzki ZA, Simons JR. Recurrent respiratory infections in a family with immunoglobulin A deficiency. Am Rev Respir Dis 1970; 101:245.
  47. Lewkonia RM, Gairdner D, Doe WF. IgA deficiency in one of identical twins. Br Med J 1976; 1:311.
  48. Gilgenkrantz S, Charles JM, Cabrol C, et al. [Deletion of the short arm of chromosome 18 due to t(22-;18p+) translocation with IgA deficiency. Cytogenetic study with autoradiography and fluorescence]. Ann Genet 1972; 15:275.
  49. Murken JD, Salzer G, Kunze D. [Ring-chromosome 18 and IgA deficiency in a 6-year-old girl (46,XX,18r)]. Z Kinderheilkd 1970; 109:1.
  50. Ogata K, Iinuma K, Kammura K, et al. A case report of a presumptive +i(18p) associated with serum IgA deficiency. Clin Genet 1977; 11:184.
  51. Schäffer AA, Pfannstiel J, Webster AD, et al. Analysis of families with common variable immunodeficiency (CVID) and IgA deficiency suggests linkage of CVID to chromosome 16q. Hum Genet 2006; 118:725.
  52. Herrmann RP, Chipper L, Bell S. Chromosomal studies in healthy blood donors with IgA deficiency. Clin Genet 1982; 22:231.
  53. Vorechovský I, Cullen M, Carrington M, et al. Fine mapping of IGAD1 in IgA deficiency and common variable immunodeficiency: identification and characterization of haplotypes shared by affected members of 101 multiple-case families. J Immunol 2000; 164:4408.
  54. Lakhanpal S, O'Duffy JD, Homburger HA, Moore SB. Evidence for linkage of IgA deficiency with the major histocompatibility complex. Mayo Clin Proc 1988; 63:461.
  55. Heikkilä M, Koistinen J, Lohman M, Koskimies S. Increased frequency of HLA-A1 and -B8 in association with total lack, but not with deficiency of serum IgA. Tissue Antigens 1984; 23:280.
  56. De La Concha EG, Fernandez-Arquero M, Martinez A, et al. HLA class II homozygosity confers susceptibility to common variable immunodeficiency (CVID). Clin Exp Immunol 1999; 116:516.
  57. Schroeder HW Jr, Zhu ZB, March RE, et al. Susceptibility locus for IgA deficiency and common variable immunodeficiency in the HLA-DR3, -B8, -A1 haplotypes. Mol Med 1998; 4:72.
  58. Olerup O, Smith CI, Hammarström L. Different amino acids at position 57 of the HLA-DQ beta chain associated with susceptibility and resistance to IgA deficiency. Nature 1990; 347:289.
  59. Pozo ND, Medrano LM, Cénit MC, et al. MSH5 is not a genetic predisposing factor for immunoglobulin A deficiency but marks the HLA-DRB1*0102 subgroup carrying susceptibility. Hum Immunol 2010; 71:861.
  60. Wang N, Shen N, Vyse TJ, et al. Selective IgA deficiency in autoimmune diseases. Mol Med 2011; 17:1383.
  61. Mohammadi J, Ramanujam R, Jarefors S, et al. IgA deficiency and the MHC: assessment of relative risk and microheterogeneity within the HLA A1 B8, DR3 (8.1) haplotype. J Clin Immunol 2010; 30:138.
  62. Sekine H, Ferreira RC, Pan-Hammarström Q, et al. Role for Msh5 in the regulation of Ig class switch recombination. Proc Natl Acad Sci U S A 2007; 104:7193.
  63. Ferreira RC, Pan-Hammarström Q, Graham RR, et al. Association of IFIH1 and other autoimmunity risk alleles with selective IgA deficiency. Nat Genet 2010; 42:777.
  64. Odineal DD, Gershwin ME. The Epidemiology and Clinical Manifestations of Autoimmunity in Selective IgA Deficiency. Clin Rev Allergy Immunol 2020; 58:107.
  65. Bronson PG, Chang D, Bhangale T, et al. Common variants at PVT1, ATG13-AMBRA1, AHI1 and CLEC16A are associated with selective IgA deficiency. Nat Genet 2016; 48:1425.
  66. Brandtzaeg P, Nilssen DE, Rognum TO, Thrane PS. Ontogeny of the mucosal immune system and IgA deficiency. Gastroenterol Clin North Am 1991; 20:397.
  67. Mella MA, Lavrinienko A, Akhi R, et al. Compensatory IgM to the Rescue: Patients with Selective IgA Deficiency Have Increased Natural IgM Antibodies to MAA-LDL and No Changes in Oral Microbiota. Immunohorizons 2021; 5:170.
  68. Mellander L, Björkander J, Carlsson B, Hanson LA. Secretory antibodies in IgA-deficient and immunosuppressed individuals. J Clin Immunol 1986; 6:284.
  69. Klemola T. Immunohistochemical findings in the intestine of IgA-deficient persons: number of intraepithelial T lymphocytes is increased. J Pediatr Gastroenterol Nutr 1988; 7:537.
  70. Sánchez Montalvo A, Gohy S, Rombaux P, et al. The Role of IgA in Chronic Upper Airway Disease: Friend or Foe? Front Allergy 2022; 3:852546.
  71. Urm SH, Yun HD, Fenta YA, et al. Asthma and risk of selective IgA deficiency or common variable immunodeficiency: a population-based case-control study. Mayo Clin Proc 2013; 88:813.
  72. Mestecky J, Zikan J, Butler WT. Immunoglobulin M and secretory immunoglobulin A: presence of a common polypeptide chain different from light chains. Science 1971; 171:1163.
  73. Savilahti E. IgA deficiency in children. Immunoglobulin-containing cells in the intestinal mucosa, immunoglobulins in secretions and serum IgA levels. Clin Exp Immunol 1973; 13:395.
  74. Low TL, Liu YS, Putnam FW. Structure, function, and evolutionary relationships of Fc domains of human immunoglobulins A, G, M, and E. Science 1976; 191:390.
  75. Abolhassani H, Aghamohammadi A, Hammarström L. Monogenic mutations associated with IgA deficiency. Expert Rev Clin Immunol 2016; 12:1321.
  76. Aytekin C, Tuygun N, Gokce S, et al. Selective IgA deficiency: clinical and laboratory features of 118 children in Turkey. J Clin Immunol 2012; 32:961.
  77. Domínguez O, Giner MT, Alsina L, et al. [Clinical phenotypes associated with selective IgA deficiency: a review of 330 cases and a proposed follow-up protocol]. An Pediatr (Barc) 2012; 76:261.
  78. Shkalim V, Monselize Y, Segal N, et al. Selective IgA deficiency in children in Israel. J Clin Immunol 2010; 30:761.
  79. Mellemkjaer L, Hammarstrom L, Andersen V, et al. Cancer risk among patients with IgA deficiency or common variable immunodeficiency and their relatives: a combined Danish and Swedish study. Clin Exp Immunol 2002; 130:495.
  80. Macpherson AJ, McCoy KD, Johansen FE, Brandtzaeg P. The immune geography of IgA induction and function. Mucosal Immunol 2008; 1:11.
  81. Ocampo CJ, Peters AT. Antibody deficiency in chronic rhinosinusitis: epidemiology and burden of illness. Am J Rhinol Allergy 2013; 27:34.
  82. Chipps BE, Talamo RC, Winkelstein JA. IgA deficiency, recurrent pneumonias, and bronchiectasis. Chest 1978; 73:519.
  83. Gomez-Carrasco JA, Barrera-Gómez MJ, García-Mouriño V, et al. Selective and partial IgA deficiency in an adolescent male with bronchiectasis. Allergol Immunopathol (Madr) 1994; 22:261.
  84. Jorgensen GH, Gardulf A, Sigurdsson MI, et al. Clinical symptoms in adults with selective IgA deficiency: a case-control study. J Clin Immunol 2013; 33:742.
  85. The 6 warning signs for primary immunodeficiency in adults were developed by the European Society for Immunodeficiencies. Available on the web at http://www.esid.org/workingparty.php?party=3&sub=2id=175.
  86. Ten warning signs for primary immunodeficiency in adults. http://www.info4pi.org/aboutPI/index.cfm?section=aboutPI&content=warningsignsadult&CFID=40450642&CFTOKEN=62808651 (Accessed on November 06, 2012).
  87. Rider NL, Truxton A, Ohrt T, et al. Validating inborn error of immunity prevalence and risk with nationally representative electronic health record data. J Allergy Clin Immunol 2024; 153:1704.
  88. Eren M, Saltik-Temizel IN, Yüce A, et al. Duodenal appearance of giardiasis in a child with selective immunoglobulin A deficiency. Pediatr Int 2007; 49:409.
  89. Carretero Gomez J, Vera Tomé A, Arévalo Lorido JC, Muñoz Sanz A. [Follicular lymphoid hyperplasia, IgA deficiency and coinfecction of Giardia lamblia and Epstein-Barr virus]. Gastroenterol Hepatol 2003; 26:397.
  90. Gato Morais R, Báñez Sánchez F, Pascual García J, et al. [Reactive arthritis due to Giardia lamblia in a patient with IgA deficiency]. An Med Interna 1998; 15:398.
  91. Langford TD, Housley MP, Boes M, et al. Central importance of immunoglobulin A in host defense against Giardia spp. Infect Immun 2002; 70:11.
  92. Istrate C, Hinkula J, Hammarström L, Svensson L. Individuals with selective IgA deficiency resolve rotavirus disease and develop higher antibody titers (IgG, IgG1) than IgA competent individuals. J Med Virol 2008; 80:531.
  93. Agarwal S, Mayer L. Pathogenesis and treatment of gastrointestinal disease in antibody deficiency syndromes. J Allergy Clin Immunol 2009; 124:658.
  94. Meini A, Pillan NM, Villanacci V, et al. Prevalence and diagnosis of celiac disease in IgA-deficient children. Ann Allergy Asthma Immunol 1996; 77:333.
  95. McGowan KE, Lyon ME, Butzner JD. Celiac disease and IgA deficiency: complications of serological testing approaches encountered in the clinic. Clin Chem 2008; 54:1203.
  96. Asada Y, Isomoto H, Shikuwa S, et al. Development of ulcerative colitis during the course of rheumatoid arthritis: Association with selective IgA deficiency. World J Gastroenterol 2006; 12:5240.
  97. Manfredi R, Coronado OV, Marinacci G, et al. Chron's disease, rare association with selective IgA immunodeficiency, and development of life-threatening bacterial infections. Scand J Infect Dis 2004; 36:523.
  98. Iizuka M, Itou H, Sato M, et al. Crohn's disease associated with selective immunoglobulin a deficiency. J Gastroenterol Hepatol 2001; 16:951.
  99. Curzio M, Bernasconi G, Gullotta R, et al. Association of ulcerative colitis, sclerosing cholangitis and cholangiocarcinoma in a patient with IgA deficiency. Endoscopy 1985; 17:123.
  100. Joo M, Shim SH, Chang SH, et al. Nodular lymphoid hyperplasia and histologic changes mimicking celiac disease, collagenous sprue, and lymphocytic colitis in a patient with selective IgA deficiency. Pathol Res Pract 2009; 205:876.
  101. Pytrus T, Iwańczak B, Iwańczak F. [Nodular lymphoid hyperplasia--underestimated problem of gastrointestinal tract pathology in children]. Pol Merkur Lekarski 2008; 24:449.
  102. Piaścik M, Rydzewska G, Pawlik M, et al. Diffuse nodular lymphoid hyperplasia of the gastrointestinal tract in patient with selective immunoglobulin A deficiency and sarcoid-like syndrome--case report. Adv Med Sci 2007; 52:296.
  103. Atarod L, Raissi A, Aghamohammadi A, et al. A review of gastrointestinal disorders in patients with primary antibody immunodeficiencies during a 10-year period (1990-2000), in children hospital medical center. Iran J Allergy Asthma Immunol 2003; 2:75.
  104. Horn J, Thon V, Bartonkova D, et al. Anti-IgA antibodies in common variable immunodeficiency (CVID): diagnostic workup and therapeutic strategy. Clin Immunol 2007; 122:156.
  105. Pineda AA, Taswell HF. Transfusion reactions associated with anti-IgA antibodies: report of four cases and review of the literature. Transfusion 1975; 15:10.
  106. Buckley RH, Schiff RI. The use of intravenous immune globulin in immunodeficiency diseases. N Engl J Med 1991; 325:110.
  107. Ferreira A, Garcia Rodriguez MC, Lopez-Trascasa M, et al. Anti-IgA antibodies in selective IgA deficiency and in primary immunodeficient patients treated with gamma-globulin. Clin Immunol Immunopathol 1988; 47:199.
  108. Sandler SG, Mallory D, Malamut D, Eckrich R. IgA anaphylactic transfusion reactions. Transfus Med Rev 1995; 9:1.
  109. Vassallo RR. Review: IgA anaphylactic transfusion reactions. Part I. Laboratory diagnosis, incidence, and supply of IgA-deficient products. Immunohematology 2004; 20:226.
  110. Hammarström L, Persson MA, Smith CI. Anti-IgA in selective IgA deficiency. In vitro effects and Ig subclass pattern of human anti-IgA. Scand J Immunol 1983; 18:509.
  111. Björkander J, Hammarström L, Smith CI, et al. Immunoglobulin prophylaxis in patients with antibody deficiency syndromes and anti-IgA antibodies. J Clin Immunol 1987; 7:8.
  112. de Albuquerque Campos R, Sato MN, da Silva Duarte AJ. IgG anti-IgA subclasses in common variable immunodeficiency and association with severe adverse reactions to intravenous immunoglobulin therapy. J Clin Immunol 2000; 20:77.
  113. Lilic D, Sewell WA. IgA deficiency: what we should-or should not-be doing. J Clin Pathol 2001; 54:337.
  114. Chowdary P, Nair D, Davies N, et al. Anaphylactic reaction with prothrombin complex concentrate in a patient with IgA deficiency and anti-IgA antibodies. Blood Coagul Fibrinolysis 2010; 21:764.
  115. Edwards E, Razvi S, Cunningham-Rundles C. IgA deficiency: clinical correlates and responses to pneumococcal vaccine. Clin Immunol 2004; 111:93.
  116. Aghamohammadi A, Cheraghi T, Gharagozlou M, et al. IgA deficiency: correlation between clinical and immunological phenotypes. J Clin Immunol 2009; 29:130.
  117. Rankin EC, Isenberg DA. IgA deficiency and SLE: prevalence in a clinic population and a review of the literature. Lupus 1997; 6:390.
  118. Yewdall V, Cameron JS, Nathan AW, et al. Systemic lupus erythematosus and IgA deficiency. J Clin Lab Immunol 1983; 10:13.
  119. Maeda M, Kitamura Y, Takata M, et al. [A case of systemic lupus erythematosus demonstrating basal ganglia calcifications, coronary stenosis and selective IgA deficiency]. Nihon Naika Gakkai Zasshi 1986; 75:83.
  120. Kanoh T, Nishimura T, Tokunaga Y. [A case of 21-year-old man with selective IgA deficiency, complicated with systemic lupus erythematosus and papillary adenocarcinoma of thyroid gland]. Nihon Naika Gakkai Zasshi 1987; 76:533.
  121. Joubert PH, Aucamp AK, Potgieter GM, Verster F. Epilepsy and IgA deficiency--the effect of sodium valproate. S Afr Med J 1977; 52:642.
  122. Pelkonen P, Savilahti E, Mäkelä AL. Persistent and transient IgA deficiency in juvenile rheumatoid arthritis. Scand J Rheumatol 1983; 12:273.
  123. Badcock LJ, Clarke S, Jones PW, et al. Abnormal IgA levels in patients with rheumatoid arthritis. Ann Rheum Dis 2003; 62:83.
  124. Kurien M, Leeds JS, Hopper AD, et al. Serological testing for coeliac disease in Type 1 diabetes mellitus: is immunoglobulin A level measurement necessary? Diabet Med 2013; 30:840.
  125. Ramanujam R, Piehl F, Pirskanen R, et al. Concomitant autoimmunity in myasthenia gravis--lack of association with IgA deficiency. J Neuroimmunol 2011; 236:118.
  126. Mantovani AP, Monclaro MP, Skare TL. Prevalence of IgA deficiency in adult systemic lupus erythematosus and the study of the association with its clinical and autoantibody profiles. Rev Bras Reumatol 2010; 50:273.
  127. Beltrán Agulló V, Saumoy Linares M, Escoda Teigell L, Ugarriza Sagaste A. [Refractory idiopathic thrombocytopenic purpura and selective IgA deficiency]. Rev Clin Esp 2002; 202:44.
  128. Abolhassani H, Gharib B, Shahinpour S, et al. Autoimmunity in patients with selective IgA deficiency. J Investig Allergol Clin Immunol 2015; 25:112.
  129. Barka N, Shen GQ, Shoenfeld Y, et al. Multireactive pattern of serum autoantibodies in asymptomatic individuals with immunoglobulin A deficiency. Clin Diagn Lab Immunol 1995; 2:469.
  130. Ammann AJ, Hong R. Selective IgA deficiency and autoimmunity. Clin Exp Immunol 1970; 7:833.
  131. Ablin RJ. Anti-tissue IgG antibodies and deficiency of IgA. Vox Sang 1972; 23:371.
  132. Wells JV, Michaeli D, Fudenberg HH. Antibodies to human collagen in subjects with selective IgA deficiency. Clin Exp Immunol 1973; 13:203.
  133. Gulez N, Karaca NE, Aksu G, Kutukculer N. Increased percentages of autoantibodies in immunoglobulin A-deficient children do not correlate with clinical manifestations. Autoimmunity 2009; 42:74.
  134. Knight AK, Bingemann T, Cole L, Cunningham-Rundles C. Frequent false positive beta human chorionic gonadotropin tests in immunoglobulin A deficiency. Clin Exp Immunol 2005; 141:333.
  135. Jorgensen GH, Thorsteinsdottir I, Gudmundsson S, et al. Familial aggregation of IgAD and autoimmunity. Clin Immunol 2009; 131:233.
  136. Cunningham-Rundles C, Brandeis WE, Pudifin DJ, et al. Autoimmunity in selective IgA deficiency: relationship to anti-bovine protein antibodies, circulating immune complexes and clinical disease. Clin Exp Immunol 1981; 45:299.
  137. Bousfiha A, Jeddane L, Picard C, et al. Human Inborn Errors of Immunity: 2019 Update of the IUIS Phenotypical Classification. J Clin Immunol 2020; 40:66.
  138. Español T, Catala M, Hernandez M, et al. Development of a common variable immunodeficiency in IgA-deficient patients. Clin Immunol Immunopathol 1996; 80:333.
  139. Aghamohammadi A, Mohammadi J, Parvaneh N, et al. Progression of selective IgA deficiency to common variable immunodeficiency. Int Arch Allergy Immunol 2008; 147:87.
  140. Gutierrez MG, Kirkpatrick CH. Progressive immunodeficiency in a patient with IgA deficiency. Ann Allergy Asthma Immunol 1997; 79:297.
  141. Slyper AH, Pietryga D. Conversion of selective IgA deficiency to common variable immunodeficiency in an adolescent female with 18q deletion syndrome. Eur J Pediatr 1997; 156:155.
  142. Litzman J, Burianova M, Thon V, Lokaj J. Progression of selective IgA deficiency to common variable immunodeficiency in a 16 year old boy. Allergol Immunopathol (Madr) 1996; 24:174.
  143. Hostoffer RW, Bay CA, Wagner K, et al. Kabuki make-up syndrome associated with an acquired hypogammaglobulinemia and anti-IgA antibodies. Clin Pediatr (Phila) 1996; 35:273.
  144. Johnson ML, Keeton LG, Zhu ZB, et al. Age-related changes in serum immunoglobulins in patients with familial IgA deficiency and common variable immunodeficiency (CVID). Clin Exp Immunol 1997; 108:477.
  145. Wilson MG, Towner JW, Forsman I, Siris E. Syndromes associated with deletion of the long arm of chromosome 18[del(18q)]. Am J Med Genet 1979; 3:155.
  146. Kato T, Crestani E, Kamae C, et al. RAG1 deficiency may present clinically as selective IgA deficiency. J Clin Immunol 2015; 35:280.
  147. Ludvigsson JF, Neovius M, Ye W, Hammarström L. IgA deficiency and risk of cancer: a population-based matched cohort study. J Clin Immunol 2015; 35:182.
  148. Conley ME, Notarangelo LD, Etzioni A. Diagnostic criteria for primary immunodeficiencies. Representing PAGID (Pan-American Group for Immunodeficiency) and ESID (European Society for Immunodeficiencies). Clin Immunol 1999; 93:190.
  149. Magen E, Geishin A, Merzon E, et al. Prevalence of neurological diseases among patients with selective IgA deficiency. Allergy Asthma Proc 2023; 44:e17.
  150. Lim CK, Dahle C, Elvin K, et al. Reversal of Immunoglobulin A Deficiency in Children. J Clin Immunol 2015; 35:87.
  151. Chapel H. Classification of primary immunodeficiency diseases by the International Union of Immunological Societies (IUIS) Expert Committee on Primary Immunodeficiency 2011. Clin Exp Immunol 2012; 168:58.
  152. Murphy EA, Morris AJ, Walker E, et al. Cyclosporine A induced colitis and acquired selective IgA deficiency in a patient with juvenile chronic arthritis. J Rheumatol 1993; 20:1397.
  153. Ashrafi M, Hosseini SA, Abolmaali S, et al. Effect of anti-epileptic drugs on serum immunoglobulin levels in children. Acta Neurol Belg 2010; 110:65.
  154. Gilhus NE, Aarli JA. The reversibility of phenytoin-induced IgA deficiency. J Neurol 1981; 226:53.
  155. Ruff ME, Pincus LG, Sampson HA. Phenytoin-induced IgA depression. Am J Dis Child 1987; 141:858.
  156. Talesnik E, Rivero SJ, González B. Serum IgA deficiency induced by prolonged phenytoin treatment. Rev Invest Clin 1989; 41:331.
  157. Braconier JH. Reversible total IgA deficiency associated with phenytoin treatment. Scand J Infect Dis 1999; 31:515.
  158. Maruyama S, Okamoto Y, Toyoshima M, et al. Immunoglobulin A deficiency following treatment with lamotrigine. Brain Dev 2016; 38:947.
  159. Kato Z, Watanabe M, Kondo N. IgG2, IgG4 and IgA deficiency possibly associated with carbamazepine treatment. Eur J Pediatr 2003; 162:209.
  160. Maeoka Y, Hara T, Dejima S, Takeshita K. IgA and IgG2 deficiency associated with zonisamide therapy: a case report. Epilepsia 1997; 38:611.
  161. Ibel H, Feist D, Endres W, Belohradsky BH. [D-penicillamine-induced IgA deficiency in the therapy of Wilson's disease]. Klin Padiatr 1990; 202:427.
  162. Götze H. [D-penicillamin-induced IgA-deficiency (author's transl)]. Klin Padiatr 1979; 191:433.
  163. Forrest RD, Boström H, Dahlberg PA. IgA deficiency during penicillamine treatment. Br Med J 1977; 1:777.
  164. Suzuki T, Okada J, Kashiwazaki S. Selective IgA deficiency developed during treatment of scleroderma kidney with captopril. J Rheumatol 1988; 15:716.
  165. Hammarström L, Smith CI, Berg CI. Captopril-induced IgA deficiency. Lancet 1991; 337:436.
  166. Farr M, Kitas GD, Tunn EJ, Bacon PA. Immunodeficiencies associated with sulphasalazine therapy in inflammatory arthritis. Br J Rheumatol 1991; 30:413.
  167. Farr M, Struthers GR, Scott DG, Bacon PA. Fenclofenac-induced selective IgA deficiency in rheumatoid arthritis. Br J Rheumatol 1985; 24:367.
  168. Stanworth DR, Williamson JP, Shadforth M, et al. Drug-induced IgA deficiency in rheumatoid arthritis. Lancet 1977; 1:1001.
  169. Seager J. IgA deficiency during treatment of infantile hypothyroidism with thyroxine. Br Med J (Clin Res Ed) 1984; 288:1562.
  170. Medical Advisory Committee of the Immune Deficiency Foundation, Shearer WT, Fleisher TA, et al. Recommendations for live viral and bacterial vaccines in immunodeficient patients and their close contacts. J Allergy Clin Immunol 2014; 133:961.
  171. American Academy of Pediatrics. Immunization and other considerations in immunocompromised children. In: Red Book: 2018 Report of the Committee on Infectious Diseases, 31st ed, Kimberlin DW, Brady MT, Jackson MA, Long SS (Eds), American Academy of Pediatrics, Itasca, IL 2018. p.72.
  172. Perez EE, Orange JS, Bonilla F, et al. Update on the use of immunoglobulin in human disease: A review of evidence. J Allergy Clin Immunol 2017; 139:S1.
  173. Smits BM, Kleine Budde I, de Vries E, et al. Immunoglobulin Replacement Therapy Versus Antibiotic Prophylaxis as Treatment for Incomplete Primary Antibody Deficiency. J Clin Immunol 2021; 41:382.
  174. Perez EE, Ballow M. Diagnosis and management of Specific Antibody Deficiency. Immunol Allergy Clin North Am 2020; 40:499.
  175. Çölkesen F, Kandemir B, Arslan Ş, et al. Relationship between Selective IgA Deficiency and COVID-19 Prognosis. Jpn J Infect Dis 2022; 75:228.
  176. Magen E, Merzon E, Green I, et al. Selective IgA deficiency and COVID-19. J Allergy Clin Immunol Pract 2023; 11:1936.
  177. Ameratunga R, Leung E, Woon ST, et al. Selective IgA Deficiency May Be an Underrecognized Risk Factor for Severe COVID-19. J Allergy Clin Immunol Pract 2023; 11:181.
  178. Quinti I, Mortari EP, Fernandez Salinas A, et al. IgA Antibodies and IgA Deficiency in SARS-CoV-2 Infection. Front Cell Infect Microbiol 2021; 11:655896.
  179. Rachid R, Bonilla FA. The role of anti-IgA antibodies in causing adverse reactions to gamma globulin infusion in immunodeficient patients: a comprehensive review of the literature. J Allergy Clin Immunol 2012; 129:628.
  180. Sandler SG, Eckrich R, Malamut D, Mallory D. Hemagglutination assays for the diagnosis and prevention of IgA anaphylactic transfusion reactions. Blood 1994; 84:2031.
  181. Burks AW, Sampson HA, Buckley RH. Anaphylactic reactions after gamma globulin administration in patients with hypogammaglobulinemia. Detection of IgE antibodies to IgA. N Engl J Med 1986; 314:560.
  182. Rachid R, Castells M, Cunningham-Rundles C, Bonilla FA. Association of anti-IgA antibodies with adverse reactions to γ-globulin infusion. J Allergy Clin Immunol 2011; 128:228.
  183. ARUP (Test ID: 2003126), performed by Eurofins Viacor.
  184. Quest Diagnostics (test ID: 92707).
  185. The American Red Cross National Lab for Specialty Testing (NRLST) offers a high sensitivity IgA test with detection limits down to <0.05 mg/dL. This is accompanied by reflex testing for anti-IgA antibodies.
  186. Gharib A, Caperton C, Gupta S. Anaphylaxis to IGIV in immunoglobulin-naïve common variable immunodeficiency patient in the absence of IgG anti-IgA antibodies: successful administration of low IgA-containing immunoglobulin. Allergy Asthma Clin Immunol 2016; 12:23.
  187. Davenport RD, Burnie KL, Barr RM. Transfusion management of patients with IgA deficiency and anti-IgA during liver transplantation. Vox Sang 1992; 63:247.
  188. Yuan S, Goldfinger D. A readily available assay for anti-immunoglobulin A: is this what we have been waiting for? Transfusion 2008; 48:2048.
  189. Brown R, Nelson M, Aklilu E, et al. An evaluation of the DiaMed assays for immunoglobulin A antibodies (anti-IgA) and IgA deficiency. Transfusion 2008; 48:2057.
  190. Meena-Leist CE, Fleming DR, Heye M, Herzig RH. The transfusion needs of an autologous bone marrow transplant patient with IgA deficiency. Transfusion 1999; 39:457.
  191. Kiani-Alikhan S, Yong PF, Grosse-Kreul D, et al. Successful desensitization to immunoglobulin A in a case of transfusion-related anaphylaxis. Transfusion 2010; 50:1897.
  192. Joller PW, Buehler AK, Hitzig WH. Transitory and persistent IgA deficiency. Reevaluation of 19 pediatric patients once found to be deficient in serum IGA. J Clin Lab Immunol 1981; 6:97.
  193. Blum PM, Hong R, Stiehm ER. Spontaneous recovery of selective IgA deficiency. Additional case reports and a review. Clin Pediatr (Phila) 1982; 21:77.
  194. Plebani A, Ugazio AG, Monafo V, Burgio GR. Clinical heterogeneity and reversibility of selective immunoglobulin A deficiency in 80 children. Lancet 1986; 1:829.
  195. Lougaris V, Sorlini A, Monfredini C, et al. Clinical and Laboratory Features of 184 Italian Pediatric Patients Affected with Selective IgA Deficiency (SIgAD): a Longitudinal Single-Center Study. J Clin Immunol 2019; 39:470.
  196. Carvalho Neves Forte W, Ferreira De Carvalho Júnior F, Damaceno N, et al. Evolution of IgA deficiency to IgG subclass deficiency and common variable immunodeficiency. Allergol Immunopathol (Madr) 2000; 28:18.
Topic 3963 Version 36.0

References

1 : Human Inborn Errors of Immunity: 2022 Update on the Classification from the International Union of Immunological Societies Expert Committee.

2 : Selective IgA deficiency.

3 : The European Society for Immunodeficiencies (ESID) Registry Working Definitions for the Clinical Diagnosis of Inborn Errors of Immunity.

4 : Practice parameter for the diagnosis and management of primary immunodeficiency.

5 : Clinical manifestation for immunoglobulin A deficiency: a systematic review and meta-analysis.

6 : Increased Fc alpha R expression and IgA-mediated function on neutrophils induced by chemoattractants.

7 : The long and winding road to IgA deficiency: causes and consequences.

8 : The four most common pediatric immunodeficiencies.

9 : Primary antibody deficiency in Arabs: first report from eastern Saudi Arabia.

10 : The Epidemiology and Clinical Presentations of Atopic Diseases in Selective IgA Deficiency.

11 : Prevalence of selective IgA deficiency in Spain: more than we thought.

12 : Selective IgA deficiency (SIgAD) in Eastern Nigeria.

13 : IgA deficiency in Czech healthy individuals and selected patient groups.

14 : Frequency of IgA deficiency in blood donors and Rh negative women in Iceland.

15 : Selective immunoglobulin A deficiency in Iranian blood donors: prevalence, laboratory and clinical findings.

16 : Screening of blood donors for IgA deficiency: a study of the donor population of south-west England.

17 : Frequency of selective IgA deficiency among Brazilian blood donors and healthy pregnant women.

18 : Screening of Canadian Blood Services donors for severe immunoglobulin A deficiency.

19 : Prevalence of selective immunoglobulin A deficiency in Greek children and adolescents with type 1 diabetes.

20 : Population-Based Screening for Selective Immunoglobulin A (IgA) Deficiency in Lithuanian Children Using a Rapid Antibody-Based Fingertip Test.

21 : [Study on immunoglobulin A Deficiency(IgAD) in Chinese Shanghai Blood Donors].

22 : The epidemiology and clinical feature of selective immunoglobulin a deficiency of Zhejiang Province in China.

23 : Prevalence of immunoglobulin A deficiency in Chinese blood donors and evaluation of anaphylactic transfusion reaction risk.

24 : [Epidemiological study of selective IgA deficiency among 6 nationalities in China].

25 : Selective IgA deficiency in Japanese blood donors: frequency and statistical analysis.

26 : Genetic linkage of IgA deficiency to the major histocompatibility complex: evidence for allele segregation distortion, parent-of-origin penetrance differences, and the role of anti-IgA antibodies in disease predisposition.

27 : Family and linkage study of selective IgA deficiency and common variable immunodeficiency.

28 : The higher frequency of IgA deficiency among Swedish twins is not explained by HLA haplotypes.

29 : Familial clustering of selective IgA deficiency.

30 : Definition of immunoglobulin A receptors on eosinophils and their enhanced expression in allergic individuals.

31 : Evaluation of effective factors on IL-10 signaling in B cells in patients with selective IgA deficiency.

32 : Interleukin-21 restores immunoglobulin production ex vivo in patients with common variable immunodeficiency and selective IgA deficiency.

33 : Increased apoptosis of CD20+ IgA + B cells is the basis for IgA deficiency: the molecular mechanism for correction in vitro by IL-10 and CD40L.

34 : The role of interleukin-6 in mucosal IgA antibody responses in vivo.

35 : Oral immunization of interleukin-4 (IL-4) knockout mice with a recombinant Salmonella strain or cholera toxin reveals that CD4+ Th2 cells producing IL-6 and IL-10 are associated with mucosal immunoglobulin A responses.

36 : B cells from p50/NF-kappa B knockout mice have selective defects in proliferation, differentiation, germ-line CH transcription, and Ig class switching.

37 : [B lymphocytes of patients with complete IgA deficiency secrete IgA in response to interleukin 10].

38 : Cytokine production in transient hypogammaglobulinemia and isolated IgA deficiency.

39 : B-lymphocyte subpopulations in patients with selective IgA deficiency.

40 : Evaluation of natural regulatory T cells in subjects with selective IgA deficiency: from senior idea to novel opportunities.

41 : Gene Signature of Regulatory T Cells Isolated from Children with Selective IgA Deficiency and Common Variable Immunodeficiency.

42 : Leveraging pleiotropy identifies common-variant associations with selective IgA deficiency.

43 : Reexamining the role of TACI coding variants in common variable immunodeficiency and selective IgA deficiency.

44 : TACI is mutant in common variable immunodeficiency and IgA deficiency.

45 : TACI mutation in common variable immunodeficiency and IgA deficiency.

46 : Recurrent respiratory infections in a family with immunoglobulin A deficiency.

47 : IgA deficiency in one of identical twins.

48 : [Deletion of the short arm of chromosome 18 due to t(22-;18p+) translocation with IgA deficiency. Cytogenetic study with autoradiography and fluorescence].

49 : [Ring-chromosome 18 and IgA deficiency in a 6-year-old girl (46,XX,18r)].

50 : A case report of a presumptive +i(18p) associated with serum IgA deficiency.

51 : Analysis of families with common variable immunodeficiency (CVID) and IgA deficiency suggests linkage of CVID to chromosome 16q.

52 : Chromosomal studies in healthy blood donors with IgA deficiency.

53 : Fine mapping of IGAD1 in IgA deficiency and common variable immunodeficiency: identification and characterization of haplotypes shared by affected members of 101 multiple-case families.

54 : Evidence for linkage of IgA deficiency with the major histocompatibility complex.

55 : Increased frequency of HLA-A1 and -B8 in association with total lack, but not with deficiency of serum IgA.

56 : HLA class II homozygosity confers susceptibility to common variable immunodeficiency (CVID).

57 : Susceptibility locus for IgA deficiency and common variable immunodeficiency in the HLA-DR3, -B8, -A1 haplotypes.

58 : Different amino acids at position 57 of the HLA-DQ beta chain associated with susceptibility and resistance to IgA deficiency.

59 : MSH5 is not a genetic predisposing factor for immunoglobulin A deficiency but marks the HLA-DRB1*0102 subgroup carrying susceptibility.

60 : Selective IgA deficiency in autoimmune diseases.

61 : IgA deficiency and the MHC: assessment of relative risk and microheterogeneity within the HLA A1 B8, DR3 (8.1) haplotype.

62 : Role for Msh5 in the regulation of Ig class switch recombination.

63 : Association of IFIH1 and other autoimmunity risk alleles with selective IgA deficiency.

64 : The Epidemiology and Clinical Manifestations of Autoimmunity in Selective IgA Deficiency.

65 : Common variants at PVT1, ATG13-AMBRA1, AHI1 and CLEC16A are associated with selective IgA deficiency.

66 : Ontogeny of the mucosal immune system and IgA deficiency.

67 : Compensatory IgM to the Rescue: Patients with Selective IgA Deficiency Have Increased Natural IgM Antibodies to MAA-LDL and No Changes in Oral Microbiota.

68 : Secretory antibodies in IgA-deficient and immunosuppressed individuals.

69 : Immunohistochemical findings in the intestine of IgA-deficient persons: number of intraepithelial T lymphocytes is increased.

70 : The Role of IgA in Chronic Upper Airway Disease: Friend or Foe?

71 : Asthma and risk of selective IgA deficiency or common variable immunodeficiency: a population-based case-control study.

72 : Immunoglobulin M and secretory immunoglobulin A: presence of a common polypeptide chain different from light chains.

73 : IgA deficiency in children. Immunoglobulin-containing cells in the intestinal mucosa, immunoglobulins in secretions and serum IgA levels.

74 : Structure, function, and evolutionary relationships of Fc domains of human immunoglobulins A, G, M, and E.

75 : Monogenic mutations associated with IgA deficiency.

76 : Selective IgA deficiency: clinical and laboratory features of 118 children in Turkey.

77 : [Clinical phenotypes associated with selective IgA deficiency: a review of 330 cases and a proposed follow-up protocol].

78 : Selective IgA deficiency in children in Israel.

79 : Cancer risk among patients with IgA deficiency or common variable immunodeficiency and their relatives: a combined Danish and Swedish study.

80 : The immune geography of IgA induction and function.

81 : Antibody deficiency in chronic rhinosinusitis: epidemiology and burden of illness.

82 : IgA deficiency, recurrent pneumonias, and bronchiectasis.

83 : Selective and partial IgA deficiency in an adolescent male with bronchiectasis.

84 : Clinical symptoms in adults with selective IgA deficiency: a case-control study.

85 : Clinical symptoms in adults with selective IgA deficiency: a case-control study.

86 : Clinical symptoms in adults with selective IgA deficiency: a case-control study.

87 : Validating inborn error of immunity prevalence and risk with nationally representative electronic health record data.

88 : Duodenal appearance of giardiasis in a child with selective immunoglobulin A deficiency.

89 : [Follicular lymphoid hyperplasia, IgA deficiency and coinfecction of Giardia lamblia and Epstein-Barr virus].

90 : [Reactive arthritis due to Giardia lamblia in a patient with IgA deficiency].

91 : Central importance of immunoglobulin A in host defense against Giardia spp.

92 : Individuals with selective IgA deficiency resolve rotavirus disease and develop higher antibody titers (IgG, IgG1) than IgA competent individuals.

93 : Pathogenesis and treatment of gastrointestinal disease in antibody deficiency syndromes.

94 : Prevalence and diagnosis of celiac disease in IgA-deficient children.

95 : Celiac disease and IgA deficiency: complications of serological testing approaches encountered in the clinic.

96 : Development of ulcerative colitis during the course of rheumatoid arthritis: Association with selective IgA deficiency.

97 : Chron's disease, rare association with selective IgA immunodeficiency, and development of life-threatening bacterial infections.

98 : Crohn's disease associated with selective immunoglobulin a deficiency.

99 : Association of ulcerative colitis, sclerosing cholangitis and cholangiocarcinoma in a patient with IgA deficiency.

100 : Nodular lymphoid hyperplasia and histologic changes mimicking celiac disease, collagenous sprue, and lymphocytic colitis in a patient with selective IgA deficiency.

101 : [Nodular lymphoid hyperplasia--underestimated problem of gastrointestinal tract pathology in children].

102 : Diffuse nodular lymphoid hyperplasia of the gastrointestinal tract in patient with selective immunoglobulin A deficiency and sarcoid-like syndrome--case report.

103 : A review of gastrointestinal disorders in patients with primary antibody immunodeficiencies during a 10-year period (1990-2000), in children hospital medical center.

104 : Anti-IgA antibodies in common variable immunodeficiency (CVID): diagnostic workup and therapeutic strategy.

105 : Transfusion reactions associated with anti-IgA antibodies: report of four cases and review of the literature.

106 : The use of intravenous immune globulin in immunodeficiency diseases.

107 : Anti-IgA antibodies in selective IgA deficiency and in primary immunodeficient patients treated with gamma-globulin.

108 : IgA anaphylactic transfusion reactions.

109 : Review: IgA anaphylactic transfusion reactions. Part I. Laboratory diagnosis, incidence, and supply of IgA-deficient products.

110 : Anti-IgA in selective IgA deficiency. In vitro effects and Ig subclass pattern of human anti-IgA.

111 : Immunoglobulin prophylaxis in patients with antibody deficiency syndromes and anti-IgA antibodies.

112 : IgG anti-IgA subclasses in common variable immunodeficiency and association with severe adverse reactions to intravenous immunoglobulin therapy.

113 : IgA deficiency: what we should-or should not-be doing.

114 : Anaphylactic reaction with prothrombin complex concentrate in a patient with IgA deficiency and anti-IgA antibodies.

115 : IgA deficiency: clinical correlates and responses to pneumococcal vaccine.

116 : IgA deficiency: correlation between clinical and immunological phenotypes.

117 : IgA deficiency and SLE: prevalence in a clinic population and a review of the literature.

118 : Systemic lupus erythematosus and IgA deficiency.

119 : [A case of systemic lupus erythematosus demonstrating basal ganglia calcifications, coronary stenosis and selective IgA deficiency].

120 : [A case of 21-year-old man with selective IgA deficiency, complicated with systemic lupus erythematosus and papillary adenocarcinoma of thyroid gland].

121 : Epilepsy and IgA deficiency--the effect of sodium valproate.

122 : Persistent and transient IgA deficiency in juvenile rheumatoid arthritis.

123 : Abnormal IgA levels in patients with rheumatoid arthritis.

124 : Serological testing for coeliac disease in Type 1 diabetes mellitus: is immunoglobulin A level measurement necessary?

125 : Concomitant autoimmunity in myasthenia gravis--lack of association with IgA deficiency.

126 : Prevalence of IgA deficiency in adult systemic lupus erythematosus and the study of the association with its clinical and autoantibody profiles.

127 : [Refractory idiopathic thrombocytopenic purpura and selective IgA deficiency].

128 : Autoimmunity in patients with selective IgA deficiency.

129 : Multireactive pattern of serum autoantibodies in asymptomatic individuals with immunoglobulin A deficiency.

130 : Selective IgA deficiency and autoimmunity.

131 : Anti-tissue IgG antibodies and deficiency of IgA.

132 : Antibodies to human collagen in subjects with selective IgA deficiency.

133 : Increased percentages of autoantibodies in immunoglobulin A-deficient children do not correlate with clinical manifestations.

134 : Frequent false positive beta human chorionic gonadotropin tests in immunoglobulin A deficiency.

135 : Familial aggregation of IgAD and autoimmunity.

136 : Autoimmunity in selective IgA deficiency: relationship to anti-bovine protein antibodies, circulating immune complexes and clinical disease.

137 : Human Inborn Errors of Immunity: 2019 Update of the IUIS Phenotypical Classification.

138 : Development of a common variable immunodeficiency in IgA-deficient patients.

139 : Progression of selective IgA deficiency to common variable immunodeficiency.

140 : Progressive immunodeficiency in a patient with IgA deficiency.

141 : Conversion of selective IgA deficiency to common variable immunodeficiency in an adolescent female with 18q deletion syndrome.

142 : Progression of selective IgA deficiency to common variable immunodeficiency in a 16 year old boy.

143 : Kabuki make-up syndrome associated with an acquired hypogammaglobulinemia and anti-IgA antibodies.

144 : Age-related changes in serum immunoglobulins in patients with familial IgA deficiency and common variable immunodeficiency (CVID).

145 : Syndromes associated with deletion of the long arm of chromosome 18[del(18q)].

146 : RAG1 deficiency may present clinically as selective IgA deficiency.

147 : IgA deficiency and risk of cancer: a population-based matched cohort study.

148 : Diagnostic criteria for primary immunodeficiencies. Representing PAGID (Pan-American Group for Immunodeficiency) and ESID (European Society for Immunodeficiencies).

149 : Prevalence of neurological diseases among patients with selective IgA deficiency.

150 : Reversal of Immunoglobulin A Deficiency in Children.

151 : Classification of primary immunodeficiency diseases by the International Union of Immunological Societies (IUIS) Expert Committee on Primary Immunodeficiency 2011.

152 : Cyclosporine A induced colitis and acquired selective IgA deficiency in a patient with juvenile chronic arthritis.

153 : Effect of anti-epileptic drugs on serum immunoglobulin levels in children.

154 : The reversibility of phenytoin-induced IgA deficiency.

155 : Phenytoin-induced IgA depression.

156 : Serum IgA deficiency induced by prolonged phenytoin treatment.

157 : Reversible total IgA deficiency associated with phenytoin treatment.

158 : Immunoglobulin A deficiency following treatment with lamotrigine.

159 : IgG2, IgG4 and IgA deficiency possibly associated with carbamazepine treatment.

160 : IgA and IgG2 deficiency associated with zonisamide therapy: a case report.

161 : [D-penicillamine-induced IgA deficiency in the therapy of Wilson's disease].

162 : [D-penicillamin-induced IgA-deficiency (author's transl)].

163 : IgA deficiency during penicillamine treatment.

164 : Selective IgA deficiency developed during treatment of scleroderma kidney with captopril.

165 : Captopril-induced IgA deficiency.

166 : Immunodeficiencies associated with sulphasalazine therapy in inflammatory arthritis.

167 : Fenclofenac-induced selective IgA deficiency in rheumatoid arthritis.

168 : Drug-induced IgA deficiency in rheumatoid arthritis.

169 : IgA deficiency during treatment of infantile hypothyroidism with thyroxine.

170 : Recommendations for live viral and bacterial vaccines in immunodeficient patients and their close contacts.

171 : Recommendations for live viral and bacterial vaccines in immunodeficient patients and their close contacts.

172 : Update on the use of immunoglobulin in human disease: A review of evidence.

173 : Immunoglobulin Replacement Therapy Versus Antibiotic Prophylaxis as Treatment for Incomplete Primary Antibody Deficiency.

174 : Diagnosis and management of Specific Antibody Deficiency.

175 : Relationship between Selective IgA Deficiency and COVID-19 Prognosis.

176 : Selective IgA deficiency and COVID-19.

177 : Selective IgA Deficiency May Be an Underrecognized Risk Factor for Severe COVID-19.

178 : IgA Antibodies and IgA Deficiency in SARS-CoV-2 Infection.

179 : The role of anti-IgA antibodies in causing adverse reactions to gamma globulin infusion in immunodeficient patients: a comprehensive review of the literature.

180 : Hemagglutination assays for the diagnosis and prevention of IgA anaphylactic transfusion reactions.

181 : Anaphylactic reactions after gamma globulin administration in patients with hypogammaglobulinemia. Detection of IgE antibodies to IgA.

182 : Association of anti-IgA antibodies with adverse reactions toγ-globulin infusion.

183 : Association of anti-IgA antibodies with adverse reactions toγ-globulin infusion.

184 : Association of anti-IgA antibodies with adverse reactions toγ-globulin infusion.

185 : Association of anti-IgA antibodies with adverse reactions toγ-globulin infusion.

186 : Anaphylaxis to IGIV in immunoglobulin-naïve common variable immunodeficiency patient in the absence of IgG anti-IgA antibodies: successful administration of low IgA-containing immunoglobulin.

187 : Transfusion management of patients with IgA deficiency and anti-IgA during liver transplantation.

188 : A readily available assay for anti-immunoglobulin A: is this what we have been waiting for?

189 : An evaluation of the DiaMed assays for immunoglobulin A antibodies (anti-IgA) and IgA deficiency.

190 : The transfusion needs of an autologous bone marrow transplant patient with IgA deficiency.

191 : Successful desensitization to immunoglobulin A in a case of transfusion-related anaphylaxis.

192 : Transitory and persistent IgA deficiency. Reevaluation of 19 pediatric patients once found to be deficient in serum IGA.

193 : Spontaneous recovery of selective IgA deficiency. Additional case reports and a review.

194 : Clinical heterogeneity and reversibility of selective immunoglobulin A deficiency in 80 children.

195 : Clinical and Laboratory Features of 184 Italian Pediatric Patients Affected with Selective IgA Deficiency (SIgAD): a Longitudinal Single-Center Study.

196 : Evolution of IgA deficiency to IgG subclass deficiency and common variable immunodeficiency.

آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟