Opinion

Crosstalk between the skeletal and immune systems—especially immunomodulation of bone turnover, but increasingly also regulation of immune functions by bone cells—was recognized during research into arthritis and has evolved into the discipline of osteoimmunology. Hiroshi Takayanagi presents an update of advances in this area, focusing on the influences of T cells on bone remodelling, and relationships between osteoblasts and haematopoiesis.

Alongside great sporting achievements, unfortunately, are inadvertent unwanted effects, as intense physical training in elite athletes can lead to long-term musculoskeletal issues. Here, Bennell and colleagues provide insights into the long-term consequences of sporting activity on the joint, in particular osteoarthritis, and describe how best to prevent and manage this damage in athletes.

In this article, the authors propose that clinical teams in the rheumatology setting are well-placed to facilitate self-management—and thereby improve health outcomes—by applying basic cognitive–behavioural techniques to helping patients manage disease-related psychological challenges and the impact of symptoms on their daily lives.

Tissue engineering and regenerative medicine hold great promise for the treatment of joint and cartilage destruction in rheumatic disease. Here, the authors describe the progress in this field, focusing on the clinical aspects of these emerging therapies and exploring the scientific and regulatory challenges in translating these tissue engineering approaches to the clinic.

Research in osteoarthritis (OA) is among the most collaborative in rheumatology, and the Osteoarthritis Initiative is championing efforts to pool expertise and data in imaging studies in OA. The rationale for, undertaking of, and emerging results from this project are outlined in this Perspectives article, with an emphasis on how they will advance the understanding and treatment of OA.

In the past decade, the introduction of targeted biologic therapies has revolutionized the treatment of rheumatic diseases. Patents for many of these key biologic agents will soon expire, and the introduction of biosimilar versions is likely to lead to substantial cost savings. Focusing on targeted therapies for rheumatic diseases, the authors describe biosimilar agent manufacture, safety and efficacy concerns, and the current worldwide status of regulations for the approval of biosimilar drugs.

Despite their different targets, biologic agents used for blockade of TNF and IL 6, inhibition of T cell co-stimulation and B cell depletion all have similar beneficial effects on the outcome of rheumatoid arthritis (RA). This observation raises questions as to whether the targets of these therapies might all be involved in a common pathogenetic pathway. In this Perspective, the authors discuss the disparities in RA therapy and whether clinical trial data can be used to determine at which point a biologic agent might interfere with the pathogenetic RA cascade.

Radiographic joint damage is strongly associated with disability in patients with rheumatoid arthritis, but the relative importance of the two major measures of radiographic damage—bone erosions and joint space narrowing—is not clearly understood. In this article, the authors discuss this issue, and describe how imaging modalities that allow detailed visualization of cartilage might lead to improved understanding.

Reactive arthritis is a form of inflammatory arthritis associated with bacterial infection. In this article, the authors describe the current state of our knowledge regardingChlamydia-induced reactive arthritis, including chlamydial persistence in joints, susceptibility factors and host and pathogen biology, and discuss future research priorities in this disease.

Increasing evidence suggests that extracellular DNA plays a part in the pathogenesis of systemic lupus erythematosus (SLE) independently of the involvement of anti-DNA autoantibodies. In this Perspectives article, the authors discuss the findings that have led to this conclusion, and explore the new therapeutic avenues that this discovery has opened. Specifically, the interesting prospect of targeting treatments at the structural manipulation of extracellular DNA is introduced and the strategies for achieving this goal that have shown promise in animal studies are presented.

Juvenile systemic sclerosis (JSSc) is a relatively rare disease compared to its adult equivalent. As a result, much of our knowledge of the disease is derived from studies in adult. Our understanding of JSSc has improved over the past 5 years, but considerable challenges remain in determining the optimal diagnostic and therapeutic protocols in these patients.

Autoantibodies, produced by autoreactive B cells, are involved in the pathology of rheumatic diseases including systemic lupus erythematosus (SLE). Modulation of B-cell function by inhibiting cytokines active on B cells or even eliminating B-cell populations can effectively treat SLE and other diseases. So far so simple, yet—as explored in this Perspective—the relationships between the effects of such therapies on B cells, the levels of individual autoantibodies, and clinical outcomes are fiendishly complex. Better knowledge of B-cell biology is needed to understand the effects of agents that target B cells, and to increase their efficacy.

A vast quantity of individual-level molecular data, including gene expression and genetic variation data, has become available in the past decade. Sirota and Butte discuss how integrative computational strategies can be applied to analyze this data across different rheumatic and autoimmune disorders. They outline the implications of such analyses, and discuss the current challenges and future directions of these approaches.

When two similar, credible analyses of the same patient database report seemingly contrasting risk estimates for the association with cancer of a widely-prescribed therapy, it is difficult for clinicians, never mind for patients, to make decisions about treatment options. Nevertheless, clinicians can—and must—interpret the available evidence for their patients, helping them to weigh the potential benefits and harms of their prescription.

Autoimmune-like syndromes (AILS), such as lupus-like syndrome and inflammatory neuropathies, are occasionally seen in patients treated with tumor necrosis factor (TNF) antagonists, although the pathogenetic mechanisms underlying these syndromes are not well understood. In this article, the author suggests that infections might trigger, amplify or mimic AILS in patients receiving anti-TNF therapy.

The disparity in the occurrence of rheumatoid arthritis (RA) between men and women is well documented, but the reasons for this difference remain poorly understood. In this article, the authors discuss the factors that might explain the sexual dimorphism of RA, including genetic, endocrine and behavioral differences, and how improving our understanding of the influence of these factors might lead to the development of novel treatments for patients with this disease.

Despite preclinical evidence of the safety and efficacy of gene therapy for arthritis, few clinical trials have been undertaken. What are the constraints on the development of this therapeutic strategy, and are these barriers likely to be overcome?

MRI has emerged as an important tool for the assessment of rheumatoid arthritis, and in research has had a clear impact on how the disease process is understood. In this Perspectives article, the authors consider the role of MRI in the evaluation of rheumatoid arthritis, including pathogenesis, diagnosis and outcomes of therapy, and examine the issues that surround the use of MRI in clinical and research settings.

In the second of two Perspectives articles regarding the use of MRI to detect inflammatory lesions in early preclinical axial spondyloarthritis, van der Heijde et al. defend the inclusion of MRI sacroiliitis in the 2009 ASAS classification criteria and acknowledge the importance of expert opinion in the diagnosis of this disease.

In the first of two Perspectives articles regarding the use of MRI to detect inflammatory lesions in early preclinical axial spondyloarthritis, De Rycke and colleagues question the diagnostic value of this technique, citing inconsistencies and selection bias in a number of validation studies.