Reviews & Analysis

In this Review, the authors summarize the changes that occur in the biocomposite formed by articular cartilage and bone during the evolution of osteoarthritis (OA). They also discuss how an improved understanding of these changes could be exploited to develop new therapies for patients with OA.

Biobanks are important tools for researchers investigating paediatric rheumatic diseases. In this Opinion article, the authors outline how standardization can improve sample and data sharing, providing examples from international biorepository networks.

Dendritic cells are key regulators of both immunity and tolerance, and display a remarkable functional heterogeneity. In this Review, the authors discuss how the function and distribution of different dendritic cell subsets change in autoimmune diseases.

Revised recommendations for the management of fibromyalgia have been published by a multinational EULAR working group. Applying these guidelines to clinical practice will require good clinical judgement and flexibility.

New research shows that an extended autoantibody repertoire is associated with adverse clinical outcomes in patients with rheumatoid arthritis. Testing for rheumatoid factor and antibodies against citrullinated proteins is now routine in the evaluation of patients with rheumatoid arthritis; should this testing be extended to include other classes of autoantibody?

Changes in DNA methylation patterns are emerging as an important feature in the development and progression of primary Sjögren syndrome. However, questions remain regarding the contribution of epigenetic (and genetic) factors to the recruitment and activation of autoreactive lymphocytes in the glandular tissues primarily affected by the disease.

Many of the 2016 updated EULAR recommendations for the management of gout lack robust evidence and rely on expert opinion, indicating gaps in our understanding of this common disease. More research is needed to fill these gaps, move towards an evidence-based approach, and improve patient care.

A new study of 'symptom-free' volunteers reports a surprisingly high prevalence of MRI features usually associated with rheumatoid arthritis (particularly bone marrow oedema), but the interpretation of these findings highlights several methodological issues. MRI assessment of healthy joints is clearly essential but should be carried out in a stringent fashion.

Adalimumab, an anti-TNF monoclonal antibody used to treat rheumatoid arthritis and other autoimmune disorders, paradoxically enhances the capacity of TNF to expand TNF receptor type II-expressing regulatory T cells. This provocative finding opens a new avenue for exploring the mechanisms that underlie efficacy, non-responsiveness and adverse effects associated with therapeutic targeting of TNF signalling.

Several lymphocyte subsets have innate-like characteristics. In this Review, the authors summarize the roles of these innate lymphocytes in autoimmunity, emphasizing that further improvements in our understanding could identify novel therapeutic targets for autoimmune diseases.

Understanding the global burden of SLE, and the factors that contribute to the considerable variation in its worldwide incidence and prevalence (particularly health disparities, costs, and socioeconomic status), is expected to inform future efforts to improve patient outcomes while optimizing resource allocation and decreasing associated health-care costs.

In this article, Cuda et al. discuss the role of programmed cell death mechanisms in the pathogenesis of rheumatic diseases, and provide an overview of the experimental data showing the function of the apoptotic machinery of phagocytes in the development of tissue inflammation.

Emerging evidence indicates that the inflammatory mechanisms involved in the pathophysiology of osteoarthritis (OA) differ from those in rheumatoid arthritis. This Review explores the mechanisms of chronic, low-grade inflammation in OA, discusses the evidence of their central role in its pathogenesis, and explores how they might be targeted to prevent or treat OA.

Cancer can be successfully treated by blocking inhibitory immune checkpoint receptors, but in some patients these treatments cause immune-related adverse effects that can resemble autoimmune responses. This Review discusses what rheumatologists can learn from these observations and summarizes progress in therapeutically targeting inhibitory receptors in autoimmune diseases.

Fibroblast-like synoviocytes isolated from the knee and hip joints of patients with rheumatoid arthritis or osteoarthritis have now been shown to have site-specific DNA methylation signatures. Although preliminary, the data point towards a new view of joint involvement in arthritis.

The type of anti-neutrophil cytoplasmic antibody (ANCA) seems to be a major determinant of clinical presentation in ANCA-associated vasculitides (AAV). The authors of this Review argue that ANCA specificity for PR3 or MPO provides clinically useful information and should be used in the classification of AAV.

Interstitial lung disease is one of the most important causes of mortality in patients with polymyositis or dermatomyositis. Understanding the risk factors for development and progression of interstitial lung disease is crucial to improving clinical outcomes.

Obesity in rheumatoid arthritis is characterized by high disease activity and low rates of remission; paradoxically, it is also associated with reduced radiographic progression. So, is intentional weight loss beneficial or detrimental to articular outcomes?

Type I interferons contribute to the pathogenesis of several autoimmune diseases, with each interferon being preferentially produced in different settings by different cells. Could knowing which one is predominant in a given disease — or patient — lead to better therapies?

This Review discusses the current treatment of the manifestations of primary Sjögren syndrome and summarizes ongoing clinical trials. The authors examine the status of biologic therapies, the challenges relating to clinical trial design and potential targets for the future therapies.