Reviews & Analysis

A growing body of evidence implicates epigenetic aberrations in systemic sclerosis pathogenesis, including epigenetic changes that affect immune cells, endothelial cells and fibroblasts, and suggests potential new avenues for therapy.

In this Review, the authors assess the current understanding of symptomatic early-stage knee osteoarthritis, including its diagnosis and classification, and highlight important gaps in knowledge that will need to be addressed to enable effective management.

New evidence has emerged that DNA can bind to cell surface HLA class II molecules. If true, this surprising interaction could lead to T cell and B cell activation by DNA, and surface DNA could also provide a target for cell killing by anti-DNA antibodies in systemic lupus erythematosus.

The development of treatments for systemic sclerosis has historically been hampered by the clinical heterogeneity of the disease and limited understanding of its pathogenesis. Encouragingly, advances including the identification of important molecular targets and improvements in clinical trial design have now greatly increased the number of investigative therapies.

Limited data suggest associations between air pollution and rheumatic disease risk and outcomes. More sophisticated research is needed to clarify the conditions under which air pollution might influence the health of people with rheumatic disease, including their response to biologic drugs.

Interactions between stromal cells and lymphocytes contribute to the pathogenesis of various autoimmune and inflammatory diseases. In this Review, the authors discuss the importance and heterogeneity of these interactions in three diseases: rheumatoid arthritis, psoriatic arthritis and systemic lupus erythematosus.

In this Review, the authors summarize and discuss the existing evidence on the incidence, prevalence and mortality of systemic lupus erythematosus across different world regions, with a focus on studies from the past 5 years.

Most rheumatic and musculoskeletal diseases (RMDs) fall along a spectrum of disorders from autoinflammatory diseases to autoimmune diseases, with ‘mixed-pattern’ RMDs having features of autoinflammation and autoimmunity. A better understanding of the pathogenic pathways of autoinflammation and autoimmunity in RMDs should enhance targeted treatment strategies.

In this Consensus Statement, members of the Gout, Hyperuricemia and Crystal-Associated Disease Network (G-CAN) highlight gaps in knowledge about the management of gout in people with chronic kidney disease, and identify important areas for future research to address challenges in the treatment of this patient population.

Hypertension and osteoarthritis are associated with each other epidemiologically and share several molecular pathways. In this Review, the authors examine the crossover between these two conditions and propose the repurposing of antihypertensive medications to treat osteoarthritis.

Physical function is an important contributor towards a patient’s quality of life, but is often neglected in management strategies for axial spondyloarthritis (axSpA). This Review provides guidance on determinants and assessments of physical function in axSpA.

Short telomere length is implicated in lung diseases and can be caused by mutations in telomere genes. Acquired autoimmunity directed against components of the telomere system is now reported in some patients with systemic sclerosis or idiopathic pulmonary fibrosis, suggesting a novel explanation for short telomeres in these diseases.

The 2021 ACR guideline for the treatment of rheumatoid arthritis provides an update on several important topics, including the use of targeted synthetic DMARDs (tsDMARDs). But how does the new guideline compare to EULAR recommendations, and is the growing importance of tsDMARDs adequately accounted for?

Lyme arthritis, a manifestation of Lyme disease, can sometimes persist in a chronic post-infectious disease. In this Review, the authors argue that post-infectious Lyme arthritis could act as a model to improve understanding of other forms of chronic arthritis.

Tumour necrosis factor (TNF) inhibitors are effective treatments for autoimmune and rheumatic diseases. Here, Salomon reviews the complex pro-inflammatory and regulatory roles of TNF, highlighting its effects on the expansion, differentiation and suppressive function of regulatory T cells and their implications for the design of future anti-TNF agents.

Genome editing technology, such as CRISPR–Cas, has great potential in the study of rheumatic disease genetics, including in discovering disease-associated genes and regulatory regions, in validating causal variants and in characterizing important cell types and cell states.

Advances in understanding the pathogenic mechanisms of primary Sjögren syndrome (pSS) and the development of new outcome measures are aiding drug development for this disease. This Review describes current treatments and highlights promising candidates for future therapies for pSS.

Sensation of mechanical stimuli by chondrocytes is critical to cartilage homeostasis and osteoarthritis development. The earliest responses in chondrocyte mechanotransduction pathways involve calcium influx and changes in mitochondrial function, which occur in seconds to minutes. Deeper understanding of these events can elucidate new therapeutic targets for early intervention to prevent osteoarthritis.

Ankylosing spondylitis (AS) is a chronic inflammatory disease with hallmarks of both autoimmune and autoinflammatory pathology. In this Review, the authors examine the evidence for both disease processes and aim to reconcile the two.

The intervertebral disc (IVD) is a hypoxic environment, and the hypoxia-inducible factor (HIF) family of transcription factors enable cells of the disc to adapt to these conditions. Understanding HIF-related mechanisms could help in the generation of therapies for IVD degeneration.