Review Articles

In this Review, Knight and Erkan consider how the 2023 ACR–EULAR classification criteria for antiphospholipid syndrome (APS) can guide future research to subphenotype APS by understanding its pathophysiology, paving the way for the personalized and proactive management of individuals with APS.

Relapsing polychondritis, a rare inflammatory disorder that affects cartilaginous structures, presents challenges in diagnosis owing to overlapping symptoms with other conditions. This Review provides a clinical update on relapsing polychondritis, emphasizing the importance of distinguishing this disease from similar conditions.

Granzyme serine proteases are known for their perforin-dependent cytotoxic activities, but evidence also indicates that they have a range of non-cytotoxic, pro-inflammatory intracellular and extracellular functions. In this Review, the authors discuss granzyme biology with an emphasis on its involvement in rheumatic disease pathology.

Early identification of osteoarthritis (OA) prior to the development of symptoms is challenging. Post-traumatic OA provides a model for the development of OA following a defined event. In this Review, the authors describe the existing knowledge relating to the biomarkers of post-traumatic OA, which might also be applicable to the identification of early non-traumatic OA.

This Review discusses joint-specific memory (the tendency of arthritis to recur in previously inflamed joints), explores the involvement of resident memory T cells and other contributors, and evaluates how arthritis might spread to new joints, emphasizing the important of sustained treatment.

Rheumatoid arthritis has a substantial genetic component, some of which is associated with the presence of low-frequency or rare variants. Next-generation sequencing in large and well-defined cohorts can continue to identify these variants and thereby contribute to the future prediction, diagnosis and treatment of rheumatoid arthritis.

Gout is associated with various cardiometabolic–renal comorbidities that increase the risk of mortality. Sodium–glucose cotransporter type 2 (SGLT2) inhibitors show promise in both addressing the symptoms of gout and managing relevant comorbidities to help prevent premature mortality.

Tyrosine kinase 2 (TYK2), a Janus kinase family member, is involved in immune signalling and is implicated in autoimmune diseases such as systemic lupus erythematosus; inhibitors of TYK2 show promise in treating various diseases and potentially offer advantages over other Janus kinase inhibitors.

Immunoengineering involves the design of materials with specific properties relating to the immune system. In this Review the authors consider the application of immunoengineering to systemic autoimmune diseases via site-specific and antigen-specific immunoregulation, the facilitation of immune cell therapy, novel approaches to immunodiagnostics and the generation of models to study autoimmunity.

Deep learning is a powerful technique with great potential for the analysis and interpretation of rheumatological images. To successfully use deep learning, rheumatologists should understand the tasks involved in image processing and the potential confounders and limitations that can affect the analysis of clinical data.

Juvenile idiopathic arthritis treatment has evolved with new therapies, early remission goals and global efforts, including randomized trials and a treat-to-target strategy. This Review summarizes current evidence and therapeutic approaches to the management of non-systemic phenotypes of juvenile idiopathic arthritis.

This Review discusses the interplay of the gut microbiome and the immune system in the context of systemic lupus erythematosus. Dysbiosis and gut-barrier dysfunction are implicated in promoting disease and are potential therapeutic targets.

This Review explores the potential of emerging RNA-based technologies and cell-engineering strategies, including those that incorporate small interfering RNA, microRNA, mRNA and synthetic receptor-mediated gene editing, to provide innovative and targeted approaches to osteoarthritis therapy.

Concerns have been raised about the safety of Janus kinase (JAK) inhibitors. This Review summarizes the evidence regarding the risks and benefits of JAK inhibitors to clarify which patients are most at risk of adverse events and guide clinical decision-making.

In this Review, the authors describe shared pathophysiology of systemic juvenile idiopathic arthritis and adult-onset Still’s disease and their life-threatening complication, macrophage activation syndrome. Therapeutic developments now enable the targeting of multiple pathways in these conditions, and evidence suggests that early use of DMARDs has the potential to prevent chronic disease.

In this epidemiological Review, the authors summarize the available evidence relating to the prevalence, incidence, risk factors and mortality associated with the autoimmune disorder Sjögren syndrome, with or without the co-occurrence of other connective tissue diseases.

In this Review, the authors discuss the role of IL-18 in human inflammatory disease. They describe the mechanisms of IL-18 biology, discuss how dysregulation of this biology leads to immunopathology, and note the biological and clinical circumstances in which therapeutic manipulation might alleviate suffering and save lives.

In this Review, the authors provide an overview of what is known of the clinical features, pathogenesis and treatment of anti-melanoma differentiation-associated protein 5 antibody-positive dermatomyositis, including emerging biomarkers and clinical subtypes.

In this Review, Pandey and Bhutani describe the use of single-cell ‘omics’ technologies to identify cell subpopulations in joint tissues in health and disease, thereby contributing to the construction of joint cell atlases and the identification of pathogenetic cell subpopulations that are potential therapeutic targets for diseases such as osteoarthritis and rheumatoid arthritis.

Depression is a common comorbidity in rheumatoid arthritis, and shared immune mechanisms link the two conditions. This Review explores potential peripheral and central interactions between the immune system and brain, the understanding of which could aid in the development of novel therapeutics.