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Transforming growth factor-β (TGF-β), a key component in altered vascular and connective tissue homeostasis, is often linked with the pathogenesis of fibrotic diseases such as systemic sclerosis (SSc). In this Review, Lafyatis highlights the known mechanisms ofin situTGF-β activation and summarizes the evidence that place TGF-β at the centre of SSc pathogenesis.
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.
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.
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.
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.
In addition to their cytotoxic, inflammatory and immunoregulatory functions, neutrophils are implicated in the pathogenesis of several autoimmune diseases, including rheumatoid arthritis. This article highlights the contributions of neutrophils to the pathophysiology of rheumatoid arthritis, focusing on the generation of autoantigens resulting from the release of neutrophil extracellular traps.
Rheumatoid arthritis (RA) is not just a disease of the joints and can be associated with ocular inflammatory conditions, including dry eye and scleritis. In this Review, the authors describe the immunopathogenic pathways that underlie ocular inflammation in RA, detailing commonalities in immune dysfunction between systemic and ocular manifestations.
Screening for the presence of antineutrophil cytoplasmic antibodies (ANCAs) is a valuable tool in the serological evaluation of systemic vasculitis disorders. In this article, Csernok and Moosig review current practice and discuss how advances in methods and strategies could improve ANCA detection and evaluation in patients with suspected vasculitis.
The pain associated with rheumatoid arthritis (RA) is complex, both in its manifestations and its underlying mechanisms. In this Review, the authors summarize what is known about the qualities of RA pain, the contributions of inflammation, peripheral and central pain processing and other factors, and discuss the range of therapeutic options available for the treatment of to this important symptom.
The diverse family of G protein-coupled receptors (GPCRs) comprises transmembrane receptors that are relevant to a range of physiological processes. Here, the authors provide an overview of GPCRs and their roles in the pathophysiology of rheumatic diseases, and discuss the potential of therapeutic approaches targeting GPCRs in these conditions.
The sialic-acid-binding immunoglobulin-type lectins (Siglecs) CD22 and Siglec–G (or the human orthologue Siglec–10) are expressed on B-cell surfaces. Here, the authors detail the involvement of CD22 and Siglec–G in maintaining B-cell tolerance, and their contribution to the prevention of autoimmune diseases. In addition, the authors describe therapeutic targeting of CD22, with antibodies and synthetic CD22 ligands, in autoimmune disease.
Fibrosis is characterized by excessive accumulation of connective tissue components in organs or tissues and is a critical, and potentially lethal, component of systemic sclerosis (SSc). Here, the authors describe the pathological role of fibrosis in the development of SSc, outlining the crucial triggers of fibrosis (including endothelium, aberrant immune responses and endoplasmic reticulum stress, among others).
The validity of research into risk factors for the development of rheumatic conditions and their sequelae can be threatened by selection bias. In this Review, the authors outline potentially major selection bias issues in rheumatic disease research and suggest approaches which could be used to help limit the impact of these biases on future research.
