Nature Reviews Rheumatology

Megan R. W. Barber, Cristina Drenkard, Titilola Falasinnu, Alberta Hoi, Anselm Mak, Nien Yee Kow, Elisabet Svenungsson, Jonna Peterson, Ann E. Clarke & Rosalind Ramsey-Goldman

doi : 10.1038/s41584-021-00668-1

Nature Reviews Rheumatology volume 17, pages515–532 (2021)

Systemic lupus erythematosus (SLE) is an autoimmune disease with protean manifestations that predominantly affects young women. Certain ethnic groups are more vulnerable than others to developing SLE and experience increased morbidity and mortality. Reports of the global incidence and prevalence of SLE vary widely, owing to inherent variation in population demographics, environmental exposures and socioeconomic factors. Differences in study design and case definitions also contribute to inconsistent reporting. Very little is known about the incidence of SLE in Africa and Australasia. Identifying and remediating such gaps in epidemiology is critical to understanding the global burden of SLE and improving patient outcomes. Mortality from SLE is still two to three times higher than that of the general population. Internationally, the frequent causes of death for patients with SLE include infection and cardiovascular disease. Even without new therapies, mortality can potentially be mitigated with enhanced quality of care. This Review focuses primarily on the past 5 years of global epidemiological studies and discusses the regional incidence and prevalence of SLE and top causes of mortality.

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Hypertension meets osteoarthritis — revisiting the vascular aetiology hypothesis

Karen Ching, Xavier Houard, Francis Berenbaum & Chunyi Wen

doi : 10.1038/s41584-021-00650-x

Nature Reviews Rheumatology volume 17, pages533–549 (2021)

Osteoarthritis (OA) is a whole-joint disease characterized by subchondral bone perfusion abnormalities and neovascular invasion into the synovium and articular cartilage. In addition to local vascular disturbance, mounting evidence suggests a pivotal role for systemic vascular pathology in the aetiology of OA. This Review outlines the current understanding of the close relationship between high blood pressure (hypertension) and OA at the crossroads of epidemiology and molecular biology. As one of the most common comorbidities in patients with OA, hypertension can disrupt joint homeostasis both biophysically and biochemically. High blood pressure can increase intraosseous pressure and cause hypoxia, which in turn triggers subchondral bone and osteochondral junction remodelling. Furthermore, systemic activation of the renin–angiotensin and endothelin systems can affect the Wnt–?-catenin signalling pathway locally to govern joint disease. The intimate relationship between hypertension and OA indicates that endothelium-targeted strategies, including re-purposed FDA-approved antihypertensive drugs, could be useful in the treatment of OA.

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Importance of lymphocyte–stromal cell interactions in autoimmune and inflammatory rheumatic diseases

Mélissa Noack & Pierre Miossec

doi : 10.1038/s41584-021-00665-4

Nature Reviews Rheumatology volume 17, pages550–564 (2021)

Interactions between lymphocytes and stromal cells have an important role in immune cell development and responses. During inflammation, stromal cells contribute to inflammation, from induction to chronicity or resolution, through direct cell interactions and through the secretion of pro-inflammatory and anti-inflammatory mediators. Stromal cells are imprinted with tissue-specific phenotypes and contribute to site-specific lymphocyte recruitment. During chronic inflammation, the modified pro-inflammatory microenvironment leads to changes in the stromal cells, which acquire a pathogenic phenotype. At the site of inflammation, infiltrating B cells and T cells interact with stromal cells. These interactions induce a plasma cell-like phenotype in B cells and T cells, associated with secretion of immunoglobulins and inflammatory cytokines, respectively. B cells and T cells also influence the stromal cells, inducing cell proliferation, molecular changes and cytokine production. This positive feedback loop contributes to disease chronicity. This Review describes the importance of these cell interactions in chronic inflammation, with a focus on human disease, using three selected autoimmune and inflammatory diseases: rheumatoid arthritis, psoriatic arthritis (and psoriasis) and systemic lupus erythematosus. Understanding the importance and disease specificity of these interactions could provide new therapeutic options.

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Treat-to-target in axial spondyloarthritis — what about physical function and activity?

Jürgen Braun, Xenofon Baraliakos & Uta Kiltz

doi : 10.1038/s41584-021-00656-5

Nature Reviews Rheumatology volume 17, pages565–576 (2021)

In patients with axial spondyloarthritis (axSpA), pain, functional and structural impairments, reduced mobility and potential deformity of the axial skeleton are the most prominent health concerns. Limitations in physical function and spinal mobility are caused by both inflammation and structural damage, and therefore restrictions to physical function must be monitored throughout a patient’s life. Consequently, the assessment of physical function is recommended as a key domain in the Assessment of Spondyloarthritis International Society–OMERACT Core Outcome Set. However, in comparison with disease activity, physical function seems to be a relatively neglected target of intervention in patients with axSpA, even though physical function is a major contributor to costs and disability in this disease. This Review aims to reacquaint rheumatologists with the targets for physical function, physical activity and performance by giving guidance on determinants of physical function and how physical function can be examined in patients with axSpA.

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Combining TNF blockade with immune checkpoint inhibitors in patients with cancer

Anne Montfort, Mathieu Virazels, Céline Colacios, Nicolas Meyer & Bruno Ségui

doi : 10.1038/s41584-021-00653-8

Nature Reviews Rheumatology volume 17, page577 (2021)

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Reply to: Combining TNF blockade with immune checkpoint inhibitors in patients with cancer

Allen Y. Chen, Jedd D. Wolchok & Anne R. Bass

doi : 10.1038/s41584-021-00654-7

Nature Reviews Rheumatology volume 17, pages577–578 (2021)

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