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Treatment of children with juvenile idiopathic arthritis (JIA) is often marred by therapeutic inefficacy and considerable adverse effects. In this Review, the authors highlight the importance of identifying new pharmacogenomics biomarkers by applying modern genome analysis to large cohorts of JIA patients, with the objective of improving safety of existing therapies and providing new drug targets for the treatment of JIA.
Despite being associated with a high rate of adverse events, biologic agents are now commonly used to treat patients with rheumatic diseases. In this comprehensive Review, the authors describe these adverse events and how rheumatologists should manage patients to treat and avoid such complications.
Although methotrexate is the main therapy for rheumatoid arthritis, surprisingly little is known about the optimal route of administration; bioavailability of methotrexate has been shown to vary accordingly. In terms of delaying a switch to biologic therapy, is the subcutaneous route superior to oral methotrexate therapy?
Rheumatoid arthritis (RA) and metabolic syndrome share several pathologic characteristics, such as changes in body composition, lipid levels and insulin sensitivity, that may increase cardiovascular mortality. Here, Kerekes and co-authors discuss associations between these components in RA and metabolic syndrome and propose that optimal therapeutic control of RA might attenuate adverse effects of metabolic syndrome in patients with RA.
Autoantibodies towards citrullinated proteins define a distinct clinical subtype of rheumatoid arthritis (RA). Here, the authors describe events triggering immunity against citrullinated proteins and argue that this immune response might be initiated outside the joint, pointing to the lungs as a possibly important site of initiation of these events.
Young adults with an acute rupture of the anterior cruciate ligament of the knee are faced with the decision of whether or not to undergo early reconstructive surgery. However, a lack of high-quality evidence means questions remain about whether this surgical strategy protects against the development of osteoarthritis in the future.
Active systemic lupus erythematosus (SLE) can manifest in heterogeneous clinical forms, making description of SLE clinical states difficult in patients with high disease activity. In this Opinion article, the authors argue the time has come to change the way SLE is managed by defining a treatment goal based on defining a low disease activity state, and they suggest possible inclusions in, and obstructions to, such a goal.
Osteoarthritis (OA) is a heterogeneous group of diseases with different pathogenesis in different joints. What effect do metabolic factors, inflammation and obesity have on OA in non-loadbearing structures? A new study reports that, in the absence of knee OA, systemic processes are important in the pathogenesis of hand OA.
Stressful life events can change the clinical expression of rheumatoid arthritis (RA). Stress increases the proinflammatory load in healthy individuals and patients with RA. A new study demonstrates that short-term experimental stress transiently increases serum IL-1β and IL-2 levels in patients with RA, but how does stress affect chronic inflammation?
A study from the Netherlands has investigated the link between rheumatoid arthritis (RA) and subfertility, finding that more aggressive disease as well as NSAID or prednisone treatment is associated with an increased time-to-pregnancy. Should methodological confounders, such as gynaecological history and psychological factors, also be assessed?
In this Review, the authors discuss the development of screening tools, outcome measures and new pharmaceutical interventions for managing patients with psoriatic arthritis (PsA). Screening tools are suggested to enable referral from dermatology clinics to rheumatologists for the diagnosis of patients early in the course of disease, and to help identify the best drugs to treat this heterogeneous disease. The authors also discuss the distinctions and similarities of 'tight control' and a treat-to-target approach for the management of PsA.
In this article, Jennette and Falk review the clinical and experimental evidence implicating antineutrophil cytoplasmic autoantibodies (ANCAs) in the pathogenesis of pauci-immune systemic necrotizing small-vessel vasculitis and glomerulonephritis. They describe the current model of ANCA-mediated vascular inflammation, involving ANCA-induced activation of primed neutrophils, and extend this theory to describe a scenario in which these antibodies could instigate extravascular granulomatosis.
The intricacies of the structure and function of eosinophils are emerging within the context of eosinophilic diseases, in particular vasculitis. In this Review, the authors describe what is known about the biology of eosinophils and their potential to cause tissue and organ damage, with a focus on the role of these cells in eosinophilic granulomatosis with polyangiitis.
SNPs ofPTPN22, a 'shared autoimmunity gene', are important risk factors for rheumatoid arthritis, juvenile idiopathic arthritis and other autoimmune diseases. In this article, Stanford and Bottini review the function of mouse and human PTPN22 in Toll-like receptor and lymphocyte antigen-receptor signalling pathways, and suggest functional models for the involvement of PTPN22 variants in the pathogenesis of autoimmune diseases.
Regulatory T (TREG) cells can be subdivided into functional subsets. In this Review the authors apply advances in our understanding of mouse and human TREG-cell biology to outline methods for TREG-cell expansion and regulation. These techniques, which include antigen-specific expansion in vitro and in vivo, could soon be used to treat patients with autoimmune rheumatic diseases.
In this Review of the clinical approach to treating patients with vasculitis, Cees G. M. Kallenberg summarizes the evolution of clinical diagnostic and classification criteria for the vasculitis syndromes. He argues that developments such as testing for ANCA specificity are the basis for a new approach to diagnosis and treatment of patients with AAV.
IL-21 regulates the activity and number of IL-10-producing regulatory B cells (B10 cells) that modulate immune responses and limit diverse autoimmune diseases. A new study demonstrates that IL-35 has a similar function. Identifying regulatory circuits that control B10-cell function in vivo might open the door to future treatments for autoimmune diseases.
Prevention of rheumatoid arthritis (RA) by intervening before the development of overt symptoms requires knowing which individuals are at risk of developing the disease. In this Review, Hunt and Emery consider several distinct at-risk cohorts, with a focus on those with systemic autoimmunity, and discuss the prospects for RA prevention in these cohorts drawing on lessons from disease prevention in other autoimmune conditions and early trials in RA.
Drawing on research in a range of disciplines, Hoffman and Calabrese provide an overview of the factors and processes that determine the unique features, functions and vulnerabilities of blood vessels in specific anatomical locations, and argue that appreciation of this diversity could lead to improved understanding of the mechanisms underlying disease patterns in the various forms of vasculitis.
Reliable estimates of disease burden support rational allocation of financial and human resources. Measurement is a powerful force for change as 'what gets measured gets done'. The global burden of musculoskeletal disease studies ensures visibility of these highly prevalent, disabling diseases. Now we must act to reduce disease burden.
