News & Views

The onset of the destructive autoimmune joint disease rheumatoid arthritis (RA) is preceded by the development of autoantibodies to multiple citrullinated proteins. Research has now shown that citrullination modifies antigen processing, resulting in the production of cryptic epitopes, suggesting a new model for RA autoantibody development.

Among the limited quality and quantity of evidence on vaccination use in individuals with rheumatic and musculoskeletal diseases, a new guideline, developed with a rigorous methodology, provides useful support to clinicians and patients in making health-related decisions. Most recommendations are conditional, serving as a call to action for further research.

Osteoarthritis has many appearances and can stabilize or progress aggressively. However, there is not yet an aetiological classification of osteoarthritis subtypes. Can in silico approaches, despite difficulties in validation, help with the identification of experimentally challenging subtypes? And if they can, will these approaches translate to clinical benefits?

The involvement of citrulline-specific CD4⁺ T cells in anti-citrulline protein antibody-positive rheumatoid arthritis (RA) is well described, whereas less attention has been given to CD8⁺ T cells. New data suggest that CD8⁺ T cells also contribute to citrulline-specific immune responses in RA.

An ambitious project to update the classification of vasculitis syndromes has culminated in the development of new classification criteria for anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, Takayasu arteritis and giant cell arteritis. Endorsed by the ACR and EULAR, the new criteria reflect progress in the understanding and assessment of these conditions.

The mechanisms underlying the genetic association between HLA-B27 and ankylosing spondylitis, including the contribution of endoplasmic reticulum aminopeptidase 1 (ERAP1), continue to elude the field. New findings support the involvement of the unfolded protein response and highlight the therapeutic potential and limitations of targeting ERAP1 in this disease.

The phenotypic and functional heterogeneity of synovial tissue fibroblasts are well described, whereas the cellular and molecular mechanisms that establish this diverse fibroblast repertoire in the adult joint have remained unclear. When is the fate of synovial fibroblast repertoire determined, and what are the consequences for arthritis development as adults?

Research related to the role of the synovium and its cell constituents during the pathogenies of osteoarthritis (OA) has taken a back seat to that of the cartilage and chondrocytes. The influence of synoviocytes in OA is increasingly recognized, but are synoviocytes equal in their contributions to disease progression?

The design of effective inhibitors of protein–protein interactions is challenging. In a new study, thermal fluctuation of protein structure was simulated to identify small-molecule candidates that inhibit protein–protein interactions. The application of this technique to other protein–protein interactions might facilitate the replacement of biologic agents with orally available small-molecule drugs.

Contemporary guidelines for the management of systemic lupus erythematosus (SLE) recommend prescribing hydroxychloroquine dosages of 5 mg/kg per day or lower to minimize toxicity. However, new evidence raises serious concerns about the risk of SLE flare associated with such doses. How do the benefits and risks of this controversial recommendation balance out?

Structural modification of RNA by adenosine-to-inosine editing renders self-RNA invisible to RNA sensors of the innate immune system. Lack of RNA editing unleashes inflammatory responses that can lead to autoinflammation. A deeper understanding of the associated signalling pathways might reveal potential targets for drug discovery for autoinflammatory diseases.

Although neutrophils are vital components of the innate immune system, they can also contribute to the inflammation and autoantibody formation that characterize a number of rheumatic diseases. The ability to specifically target neutrophils, and in particular activated neutrophils, could enable the direct delivery of drugs for therapeutic modulation of neutrophil activity.

Glucocorticoids are common medications that are used in research trials and clinical practice. Measuring the toxicity of glucocorticoids in children is complicated by various factors such as age and growth. A standardized tool could help to record these toxicities across different specialities in a systematic manner.

New research reinforces the fact that most recommendations in rheumatology are not informed by comparative efficacy randomized controlled trials. Performing these studies is time and resource intensive. Policies and funding to perform these studies in a timely and resource constraint manner are essential.

Often viewed as merely an inconsequential episode of acute joint pain, gout flare has also been associated with an increased risk of acute myocardial infarction and stroke. New findings suggest the risk is highest within the first 60 days of gout flare, and could be influenced by flare treatment.

New research shows that TNF can directly induce osteoclastogenesis from transforming growth factor-β (TGFβ)-primed macrophages and that knockout of TGFβ signalling limits TNF-induced arthritic bone erosion in mice, suggesting that TGFβ inhibition could enhance the effect of anti-TNF therapy in rheumatoid arthritis.

Transitional care in rheumatology has been debated for over three decades and yet unmet needs of young people are still being reported. Why the slow progress? Perhaps we need to stop talking about transitional care in rheumatology and talk more about developmentally appropriate health care for young people with rheumatic conditions.

Multisystem inflammatory syndrome in children (MIS-C) and Kawasaki disease are both hyperinflammatory disorders associated with infectious diseases, but are they distinct syndromes or do they exist along a continuum? A comparison of the host immune response in these illnesses provides surprising new insights.

Lack of understanding of the immunology of sarcoidosis has limited therapeutic progress. However, evidence from a small open-label trial suggests that treatment with the Janus kinase inhibitor tofacitinib can improve sarcoidosis symptoms, predominantly by inhibiting type 1 immunity.

In patients with autoimmune rheumatic disease, methotrexate therapy has been associated with poor immune response to vaccines, including those intended to provide protection against COVID-19. Emerging evidence supports the practice of temporarily discontinuing this treatment in order to improve immunogenicity.