Reviews & Analysis

In this Perspective, the authors and the members of the Integrated Multidisciplinary Paediatric Autoimmunity and Cell Therapy (IMPACT) working group discuss specific considerations for the use of chimeric antigen receptor (CAR) T cell therapies in paediatric patients with rheumatic diseases.

Systemic lupus erythematosus is characterized by altered metabolic profiles and changes in immune cell metabolism. The authors review these changes and discuss how interventions that target metabolic processes might provide treatment options in systemic lupus erythematosus.

In this Consensus Statement, an international group of experts and patient representatives validates and endorses the transition from the term ‘Sjögren syndrome’ to ‘Sjögren disease’, and issue several additional recommendations regarding the nomenclature of this disorder.

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is caused by somatic mutations in UBA1 arising in hematopoietic stem cells, resulting in systemic autoinflammation and clonal outgrowth of these mutant cells. New research provides insights into the paradoxical mechanism behind this clonal hematopoietic dominance.

This Review discusses the advances and challenges of managing antineutrophil cytoplasmic antibody-associated vasculitis. The authors discuss current treatment options, emerging therapies and unmet needs in the management of this disease.

The increased incidence of deep vein thromboses and pulmonary emboli has long been noted in rheumatoid arthritis and has been ascribed to the effects of chronic inflammation and disease activity, as well as to specific biologic DMARDs and JAK inhibitors. Reporting in ACR Open Rheumatology, Zavoriti and Miossec provide data that might explain the prothrombotic effects of the JAK inhibitor tofacitinib.

This Review discusses the clinical features, pathogenesis, diagnosis and management of monogenic forms of vasculitis. The authors emphasize that increased awareness of these rare diseases could aid earlier diagnosis and better, more-targeted treatment options for patients.

This Review provides a comprehensive overview of fibroblast biology in rheumatoid arthritis and other chronic inflammatory diseases. The authors discuss insights into fibroblast behaviour and pathogenicity from single-cell and functional studies and describe how these findings have informed efforts to therapeutically target fibroblasts.

Separate guidelines are needed for the management and diagnosis of rheumatic diseases in low- and middle-income countries, especially with the advent of expensive biological therapies and monitoring techniques. The lack of robust data on the efficacy of low-cost drugs and biosimilars in these countries limits the development of data-driven guidelines.

This Review explores the ongoing debate regarding the definition of cell identity, with a focus on the immune and stromal cell landscape within rheumatology. The authors discuss the implications of different frameworks of cell identity for disease treatment and the discovery of predictive biomarkers for stratified medicine.

Systemic vasculitis, including monogenic forms, is associated with an increased risk of arterial and venous thromboembolic events (AVTEs). This Review highlights the latest advances in the understanding of the pathogenesis, clinical features and management of AVTEs in systemic and monogenic vasculitis.

In joints with osteoarthritis, angiogenesis and neuronal growth occur at the osteochondral junction, a process that can contribute to structural joint damage and pain. Targeting this neurovascularization process represents a possible strategy for the development of disease-modifying drugs for osteoarthritis.

A simple blood test that can diagnose or predict one’s risk for autoimmune diseases would revolutionize medicine and transform patient care. Published in Science, Zaslavsky et al. advance this vision with a powerful machine learning framework that leverages immune receptor sequences from T cells and B cells for disease classification.

IgG4-related disease is a fibro-inflammatory disorder with a complex pathogenesis. Herein the authors review the latest developments in IgG4-related disease clinical phenotyping, pathophysiology and management, with a focus on the main mimics of this disease and how to approach issues related to differential diagnosis.

This Review discusses how pain in osteoarthritis might involve adaptations of brain circuits, and suggests that osteoarthritis pain management should consider targeting central mechanisms of pain in addition to nociceptive neuron activity.

Insights from the composition, structure and development of articular cartilage are key for long-term therapeutic strategies to restore articular cartilage. The authors emphasize that future therapies should replicate the depth-dependent alignment of collagen and its interactions with the extracellular matrix to produce implants that mimic the biomechanical properties of cartilage.

Molecular imaging techniques such as PET with the leukocyte-targeted probe ⁸⁹Zr-CD45 are promising tools for rheumatology, providing a non-invasive whole-body assessment of the mechanisms that drive tissue inflammation. These techniques could improve diagnosis and disease monitoring, but further research is required before clinical implementation.

Treating people with inflammatory arthritis and cancer is challenging given concerns around suppressing anti-tumour immunity. Targeted therapies, such as TNF inhibitors, can be safely used in patients with cancer who are in remission, but whether these treatments are safe for individuals with newly diagnosed or active cancer remains unclear.

This Review provides an update on the role of innate and adaptive immune cells in the pathogenesis of osteoarthritis. The authors discuss emerging therapeutics that target the immune system in osteoarthritis and the challenges that limit the movement towards personalized medicine.

In this Perspective, the authors propose that patients with psoriatic arthritis and an inadequate response to therapy can be classified into two distinct subgroups, characterized by persistent inflammatory and non-inflammatory phenotypes, and discuss potential mechanisms underlying these phenotypes, as well as considerations for treatment strategies and trial design.