News & Views

Exactly how nucleic acids trigger type I interferon responses via certain Toll-like receptors has been uncertain. Now, a new pathway involving gene products previously linked to systemic lupus erythematosus but not known to interact has been unravelled, which could be of relevance to the female sex bias in this disease.

Early diagnosis of immune-mediated arthropathies is important for early and effective treatment, but often relies on clinical expertise. Can the use of a new genetic risk score help rule out and prioritize certain diagnoses? And does this score add any clinical utility to current clinical diagnostic pathways?

The ACR has published an update to its guideline on gout management, which was mostly based on the results of randomized controlled trials (RCTs). Although rigorous, the methodology used for these recommendations can be called into questioned given the lack of robust data from RCTs on all aspects of gout.

Researchers have developed an in silico (computer) platform that couples tissue adaptation with cellular and molecular interactions to simulate bone adaptation to mechanical loading and progress and treatment of metabolic bone diseases. What is the benefit of such in silico tools, and how can credibility of the simulation outcomes be established?

Rheumatologists lack guidance on how to manage the reproductive health of their patients, and communication to patients on reproductive health issues is an unmet need. New guidelines from the ACR provide support in the counselling of both female and male patients on the different aspects of their reproductive life.

Results from phase II randomized controlled trials (RCTs) determine whether promising therapeutics will progress to phase III. According to detailed analyses in rheumatoid arthritis and psoriatic arthritis, phase II efficacy data systematically overestimate subsequent phase III results, raising the question of how this discrepancy might be addressed in future RCTs.

The COVID-19 pandemic has catalysed the sudden adoption of telemedicine in the management of rheumatic diseases. In this abrupt transition from in-person visits to telemedicine, can patient-reported outcomes (PROs) help ensure that we continue to achieve optimum disease control and address the concerns of people living with rheumatoid arthritis?

Emerging reports show that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection precedes the appearance of various autoimmune and autoinflammatory diseases, including paediatric inflammatory multisystemic syndrome (PIMS) or multisystem inflammatory syndrome in children (MIS-C), thus adding to the growing mystery of this virus and raising questions about the nature of its link with autoimmune and autoinflammatory sequelae.

The heterogeneity of systemic lupus erythematosus (SLE) confounds the diagnosis and treatment of this disease, and attempts at disease stratification are nascent. Researchers have identified a common set of biomarkers in patients with SLE that could identify new therapeutic targets and lead to new clinical assays to help address this issue.

Baseline immune variation predicts immune responses during vaccination, and the gene signatures capturing such immune variation seem to correlate with systemic lupus erythematosus (SLE) disease activity. Will the definition of these gene sets enable the development of the much needed concept of personalized medicine in SLE?

Idiopathic inflammatory myopathies (IIMs) are heterogeneous conditions, and the optimal way to classify patients and divide them into subgroups remains unclear. Could machine learning techniques be the answer to the problem of defining homogeneous disease phenotypes, enabling stratified treatment approaches and the formulation of future IIM classification criteria?

Methotrexate is commonly used in combination with biologic DMARDs in the treatment of rheumatoid arthritis on the basis that the combined therapy has synergistic benefits. New data challenge this concept in the treatment of older adults and highlight the uncertainty of the mode of action of methotrexate in this population.

New research suggests that cytotoxic T cells are dominant in the lesional skin of patients with early diffuse cutaneous systemic sclerosis (SSc) and contribute to vasculopathy and tissue fibrosis. Could therapeutic strategies that prevent T cell activation and cytotoxicity therefore present an option to potentially halt progression of SSc?

Children and young people with rheumatic diseases face considerable challenges to their mental health, yet the research guiding prevention and intervention strategies is limited. A new research agenda provides an important step forward by highlighting important issues, but can these research priorities be addressed within the paediatric rheumatology health-care context?

Patients with clinically suspect arthralgia have articular symptoms such as pain and stiffness of the small joints without clinical signs of arthritis. Some of these patients progress and develop ‘true’ disease, but how can we differentiate evolving chronic disease from disease that will resolve?

Newly discovered small-molecule TNF inhibitors serve as antagonists of pro-inflammatory TNF signalling by uniquely harnessing the conformational plasticity of trimeric TNF. The development of this approach could mark a resurgence of non-biologic modulators of clinically relevant protein–protein interactions in rheumatology.

Trials studying rare diseases, including immune-mediated inflammatory diseases such as Castleman disease, hyper IgD syndrome and undifferentiated vasculitis, frequently end in noncompletion and nonpublication. A new cross-sectional analysis identifies underlying reasons, but also calls for action to establish international networks that might facilitate recruitment of patients into trials and to ensure timely publication of research findings to advance the field.

Obesity promotes osteoarthritis (OA) through complex and incompletely understood biomechanical, metabolic and inflammatory factors. New data in mice add to this complexity by showing that eating a high-fat diet increases the risk of OA for two generations of offspring, raising questions about disease mechanisms and future treatment strategies.

B cells can assume protective or pathogenic roles in immune-mediated diseases (IMDs). Analysis of the B cell receptor (BCR) repertoires in six IMDs provides insights into the diversity of B cell repertoires across diseases as well as into potential pathological mechanisms and the effects of different treatments.

NSAIDs are first line therapy for patients with axial spondyloarthritis and are recommended to be taken continuously in patients with active disease, but their ability to affect radiographic disease progression has been uncertain. Does a new meta-analysis shed light on this matter, or is it too soon to tell?