Summary of IUIS classification groups for inborn errors of immunity (primary immunodeficiencies)^[1-3]

IUIS classification group	IEI disease category	Number of genes^*	Characteristics	Examples
I	Immunodeficiencies affecting cellular and humoral immunity	73	Recurrent viral, fungal, and bacterial infections Autoimmunity	SCID DOCK8 deficiency CD40L deficiency MHC I/II deficiency
II	Combined immunodeficiencies with associated or syndromic features	83	Recurrent viral, fungal, and bacterial infections Autoimmunity Nonimmune features Dysmorphology	Hyper-IgE (STAT3) Wiskott-Aldrich syndrome Cartilage-hair hypoplasia 22q11.2 deletion syndrome NEMO deficiency
III	Predominantly antibody deficiencies	48	Recurrent bacterial sinopulmonary infections	X-linked (BTK) and autosomal recessive agammaglobulinemia Autosomal recessive hyper-IgM Selective IgA deficiency
IV	Diseases of immune dysregulation	72	Lymphoproliferation Autoimmunity Hemophagocytic lymphohistiocytosis	Chediak-Higashi syndrome Perforin deficiency ALPS STAT3 gain of function CTLA4 deficiency LRBA deficiency IL-10 deficiency
V	Congenital defects of phagocyte number or function	45	Severe bacterial infections of the skin, lungs, and lymph nodes Inflammatory bowel disease	Chronic granulomatous disease Leukocyte adhesion deficiency GATA2 deficiency Congenital neutropenias
VI	Defects in intrinsic and innate immunity	86	Invasive bacterial infections (sepsis, meningitis) often in the absence of fever Recurrent fungal, mycobacterial, and viral infections	IRAK4 and MyD88 deficiency STAT1 gain of function Interferon gamma receptor deficiency IRF7 deficiency TLR3 deficiency
VII	Autoinflammatory disorders	69	Recurrent fever, rash, arthritis/arthralgia Amyloidosis Inflammatory bowel disease	Familial Mediterranean fever Mevalonate kinase deficiency Muckle-Wells syndrome NLRP1 deficiency
VIII	Complement deficiencies	36	Disseminated neisserial infections Recurrent pyogenic infections SLE Atypical hemolytic uremic syndrome	Deficiency of complement components (C1 to C9) Properdin deficiency Factor D deficiency Factor H deficiency
IX	Bone marrow failure	47	Macrocytic anemia and other cytopenias Skeletal, nail, hair, and/or skin abnormalities	Fanconi anemia Dyskeratosis congenita
X	Phenocopies of IEI associated with autoantibodies or somatic variants	17	Various phenotypes	ALPS-SFAS (somatic mutations in TNFRSF6) Mucocutaneous candidiasis due to autoantibodies to IL-17 or IL-22 Mycobacterial infections due to autoantibodies to IL-6 Acquired angioedema due to autoantibodies to C1 inhibitor Severe, life-threatening infections with SARS-CoV-2 due to autoantibodies to type 1 interferons (IFN-alpha and IFN-omega)

Summary of the major classification groups in the 2024 IUIS report.^[3]

ALPS: autoimmune lymphoproliferative syndrome; ALPS-SFAS: autoimmune lymphoproliferative syndrome due to somatic FAS mutation; BTK: Bruton tyrosine kinase; CD40L: CD40 ligand; CTLA4: cytotoxic T lymphocyte-associated antigen 4; DOCK8: dedicator of cytokinesis 8; GATA2: GATA-binding protein 2; IEI: inborn errors of immunity; IFN: interferon; IgA: immunoglobulin A; IgE: immunoglobulin E; IgM: immunoglobulin M; IL: interleukin; IRAK4: IL-1 receptor-associated kinase 4; IRF7: interferon regulatory factor 7; IUIS: International Union of Immunological Societies; LRBA: lipopolysaccharide-responsive beige-like anchor; MHC: major histocompatibility complex; MyD88: myeloid differentiation primary response protein 88; NEMO: nuclear factor-kappa-B essential modifier; NLRP1: NLR family pyrin domain-containing 1; SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; SCID: severe combined immunodeficiency; SLE: systemic lupus erythematosus; STAT1: signal transducer and activator of transcription 1; STAT3: signal transducer and activator of transcription 3; TLR3: toll-like receptor 3; TNFRSF6: tumor necrosis factor receptor superfamily member 6.

* Number of genes as of April 2025.

References:

Picard C, Bobby Gaspar H, Al-Herz W, et al. International Union of Immunological Societies: 2017 Primary Immunodeficiency Diseases Committee Report on Inborn Errors of Immunity. J Clin Immunol 2018; 38:96.
Yu JE, Orange JS, Demirdag YY. New primary immunodeficiency diseases: Context and future. Curr Opin Pediatr 2018; 30:806.
Poli C, Aksentijevich I, Bousfiha A, et al. Human inborn errors of immunity: 2024 update on the classification from the International Union of Immunological Societies Expert Committee. J Hum Immun 2025; 1:e20250003.

Graphic 121770 Version 4.0

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Summary of IUIS classification groups for inborn errors of immunity (primary immunodeficiencies)[1-3]

Summary of IUIS classification groups for inborn errors of immunity (primary immunodeficiencies)^[1-3]