Reviews & Analysis

The pathways involved in sensing and responding to mechanical stimuli have important roles in maintaining cartilage health, and can contribute to disease when dysregulated. This Review discusses cartilage mechanosignalling pathways and how they can be targeted to treat osteoarthritis.

In this Review, Choi et al. review the pathogenesis of cardiometabolic-renal comorbidities of gout and discuss potential therapies to concurrently reduce serum urate concentrations and risk of gout cardiometabolic-renal comorbidities.

In this Review, the authors summarize the clinical features, management and prognosis of acute exacerbation of interstitial lung disease in patients with rheumatic diseases, and discuss the definitions and diagnostic criteria for this often life-threatening condition.

Vasculitis, inflammation of the blood vessels, takes many forms and can affect every organ system, potentially causing kidney failure, vision loss and death. This Review describes current knowledge on the global incidence and prevalence patterns for various types of vasculitis.

In this Review, the authors introduce the application of artificial intelligence, in particular machine learning and deep learning, for improving multiple stages of MRI, including acquisition, processing and post-processing steps, for studying osteoarthritis.

In this Review, the authors discuss the immunometabolic alterations involved in the pathogenesis of intervertebral disc degeneration, including the role of adipokines in impaired metabolism in intervertebral disc cells, and discuss opportunities for future research and development of new therapies.

Differentiating between the early stages of systemic lupus erythematosus (SLE) and undifferentiated connective tissue disease (UCTD) can be challenging. In this Review, the authors summarize current knowledge on UCTD and early-stage SLE and discuss clinical approaches to diagnosing these conditions.

In this Review, the authors provide an introduction to machine learning and discuss the use of this approach in rheumatic autoimmune inflammatory diseases, including the classification of patients based on medical records or molecular characteristics, identification of novel biomarkers or drug repurposing candidates and prediction of disease progression or onset.

Regulatory T (T_reg) cells have crucial roles in peripheral tolerance and limiting inflammation, and IL-2 is an important cytokine for T_reg cell differentiation, activity and homeostasis. In this Review, Kolios, Tsokos and Klatzmann provide an overview of T_reg cell and IL-2 involvement in rheumatic diseases and how modulating IL-2 signalling and T_reg cell biology might provide novel treatment avenues.

In this timely Review, the authors compare and contrast two forms of childhood inflammatory vasculitis: Kawasaki disease and the coronavirus disease 2019 (COVID-19)-associated multisystem inflammatory syndrome in children, highlighting epidemiological, clinical and immunological differences that suggest they should be classified as distinct syndromes.

Knee joint distraction (KJD) is used to stimulate joint repair in advanced osteoarthritis. In the Review, Jansen and Mastbergen provide an overview of the clinical trial results of KJD treatment, current knowledge of the molecular mechanisms underlying joint repair in KJD, and future directions and unanswered questions in KJD research and treatment.

Interferon-γ (IFNγ) is important in innate and adaptive immunity and its overproduction is also implicated in hyperinflammation. Here, De Benedetti and colleagues discuss the evidence for a pathogenetic role of IFNγ in hyperinflammatory diseases, the search for IFNγ biomarkers, and the results of clinical trials of IFNγ-neutralizing therapeutics.

Fatigue is a common and debilitating symptom of inflammatory rheumatic diseases, but the underlying mechanisms remain poorly understood. In this Review, the authors examine the potential contributing factors, present putative models of fatigue and discuss challenges for research and treatment.

Non-coding RNAs such as microRNAs, long non-coding RNAs and circular RNAs regulate signalling pathways that are important in joint development, homeostasis and disease. A better understanding of the non-coding RNA interactome could lead to new therapies for joint diseases.

Analysis of the microcirculation is useful in the differential diagnosis of primary and secondary Raynaud phenomenon and in the diagnosis and monitoring of several rheumatic diseases, including systemic sclerosis. This Review provides an overview of techniques for microvascular analysis.

Blood vessels perform vital roles in the skeletal system during development and homeostasis, and both participate in and are affected by inflammation. In this Review, the authors highlight the roles of endothelial cells during bone development, homeostasis and disease.

A growing body of evidence implicates epigenetic aberrations in systemic sclerosis pathogenesis, including epigenetic changes that affect immune cells, endothelial cells and fibroblasts, and suggests potential new avenues for therapy.

In this Review, the authors assess the current understanding of symptomatic early-stage knee osteoarthritis, including its diagnosis and classification, and highlight important gaps in knowledge that will need to be addressed to enable effective management.

Interactions between stromal cells and lymphocytes contribute to the pathogenesis of various autoimmune and inflammatory diseases. In this Review, the authors discuss the importance and heterogeneity of these interactions in three diseases: rheumatoid arthritis, psoriatic arthritis and systemic lupus erythematosus.

In this Review, the authors summarize and discuss the existing evidence on the incidence, prevalence and mortality of systemic lupus erythematosus across different world regions, with a focus on studies from the past 5 years.