Reviews & Analysis

2014 saw the emergence of a novel rheumatoid arthritis therapy to rival methotrexate, as well as advances in our understanding of mouse T-cell biology and of the cross-talk between the nervous system and the immune system. How will these advances affect the future of rheumatoid arthritis research and therapy?

Three monogenic diseases, with features of both autoinflammation and autoimmunity, were described for the first time in 2014. As well as providing insights into the molecular basis of several rare immunological disorders, the discoveries have implications for their diagnosis and treatment.

Next-generation sequencing is at the forefront of the identification and characterization of clonal families of antibodies that are involved in immune responses to infection, cancer and autoimmune disease. In this article, cutting-edge antibody repertoire sequencing technologies are described as a means of paving the way forward for research and discovery in rheumatology.

This article places Raynaud phenomenon in the context of a mechanistic understanding of cutaneous vasoconstrictive and thermoregulatory processes, describing how these processes might regulate the pathogenesis of Raynaud phenomenon and ultimately inform new approaches to its treatment.

Despite having a poor intrinsic capacity for repair, articular cartilage has been shown to contain a population of self-renewing, multipotent cells that express stem-cell-related surface markers. In this article, Jiang and Tuan review what is known about these cartilage-derived stem/progenitor cells, with a focus on their origin, function and therapeutic potential in osteoarthritis.

Important advances in 2014 foster new perspectives on definitions of early and end-stage disease, and promote a shift in the clinical management of osteoarthritis (OA) through implementing treatment algorithms intended to minimize strain on current health-care models. Collectively, these changes shed new light on developing and optimizing approaches to OA treatment.

Can a patient's genotype provide insight into the mechanistic basis of autoimmune disease? A study integrating epigenetic data with finely mapped disease-associated variants sheds light on how noncoding variants might alter gene expression within specific immune cells, and hints at new possibilities for individualizing treatment of autoimmune rheumatic disorders.

Disease-modifying osteoarthritis (OA) drugs (DMOADs) are needed as current OA therapies only relieve pain and do not alter the course of disease. In this article, Toll-like receptor 4 (TLR4) signalling, which is involved at various stages of pathogenesis, is reviewed, as is the potential for candidate TLR4-specific DMOADs.

Promising biomarkers are being developed to predict disease outcome and response to therapy in children with juvenile idiopathic arthritis, childhood lupus nephritis and juvenile idiopathic inflammatory myopathies. These advances are expected to facilitate risk stratification, diagnosis and management of these patients, and thereby lead to more rational and effective clinical care.

Patients with autoimmune inflammatory rheumatic diseases have an impaired immune system that can be exacerbated by medication, making them susceptible to infectious diseases. This article reviews this problem and the potential compounding issue that vaccinating these patients against common infectious diseases is not always safe and effective.

Basophils are classically known for their pathogenic role in asthma and allergic skin conditions. However, reports suggest that basophil activation mediated by autoreactive IgE, thymic stromal lymphopoietin or Toll-like receptors has an important role in the pathogenesis of lupus nephritis, eosinophilic oesophagitis and IgG4-related diseases, respectively.

In this Perspectives article, the authors argue that the cells of the inflammatory infiltrate and the cytokine milieu provide multiple routes to bone destruction in inflammatory arthritis. They first summarize the physiological pathway of osteoclastogenesis, then present emerging evidence of the contribution of various cytokines and cell types to alternative pathways of osteoclast differentiation and activation.

Contrary to earlier beliefs, evidence now exists that exercise does not exacerbate systemic inflammatory diseases, such as rheumatoid arthritis. In this Review of exercise therapy for rheumatic diseases, the authors propose that, by interrupting a cycle of local inflammation, obesity, metabolic dysregulation and systemic inflammation, exercise is medicine.

The presence or absence of autoantibodies in patients with rheumatoid arthritis (RA) can guide clinical practice, but the role of autoantibody status in 'real life' is unclear. A cohort study from Canada provides clinical perspective on the presentation, prognosis and efficacy of treatment of patients with autoantibody-negative RA.

The positive results of the phase II programme of fostamatinib, developed to target the spleen tyrosine kinase pathway in rheumatoid arthritis (RA), have not been replicated in phase III. What implications might the results have for the development of other oral inhibitors of intracellular kinases in the treatment of RA?

In systemic sclerosis (SSc), new classification criteria highly sensitive to early and limited forms of the disease could facilitate not only the recognition of early SSc, but also the discovery of biomarkers of poor prognosis, with potential benefits for conducting clinical trials.

Glucocorticoid therapy is associated with bone loss and increased risk of fracture, but these deleterious effects can be avoided or mitigated with appropriate treatment. When to initiate anti-osteoporosis therapy and what form this preventive therapy should take is the focus of this Review.

The ASAS classification criteria for axial and peripheral subgroups are beginning to alter our understanding of spondyloarthritis. In this article, Astrid van Tubergen discusses how these criteria are changing not only our clinical understanding, but also the epidemiology, including prevalence and incidence calculations.

Epigenetic regulation is a vital driver of the aetiology of human disease, with research breakthroughs now occurring on a regular basis. Several studies investigating CpG methylation of cartilage DNA from patients with osteoarthritis are generating exciting insight into this common but complex disease.

In comparison with traditional surgery techniques, arthroscopic surgeries induce less tissue damage and can reduce morbidity and complications. In this Review, Carr and colleagues focus on the increased use of therapeutic arthroscopy as a tool for excision, reconstruction and replacement of damaged or abnormal tissue, and signal the need for additional studies to allow this surgical approach to reach its full potential.