Reviews & Analysis

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.

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.

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.

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.

A group of experts in rheumatology and dermatology has identified many unmet needs in the care of patients with psoriatic arthritis and offered potential solutions. But do their recommendations go far enough?

The strongest evidence yet that hypertrophic chondrocytes can turn into osteoblasts could affect not only our understanding of skeletal development, but also the use of research tools thought to be cartilage-specific.

Patients with rheumatoid arthritis who are hemiplegic, and also mice with denervated hindpaws and experimentally-induced arthritis, can develop unilateral arthritis. But is a specific branch of the nervous system involved in this asymmetry, or does a lack of innervation alter the microvasculature and promote vascular impermeability?

Macrophage activation syndrome (MAS) in systemic juvenile idiopathic arthritis (sJIA) is difficult to distinguish from active sJIA or sepsis. A collaborative effort scoring the performance of different clinical diagnostic criteria provides valuable guidance to clinicians, but challenges in the diagnosis of sJIA-related MAS remain.

A lack of universally accepted classification criteria for patients with juvenile spondyloarthritis (SpA) has hindered efforts to develop tools to assess the severity and progression of this disease. With the publication of a new juvenile SpA disease activity index, has this gap now been bridged, and is it a comprehensive tool for the clinic?

Given the known involvement of IL-36 in psoriasis it might be surprising that the latest mouse models show that inhibiting IL-36 signalling does not alter the course of inflammatory arthritis. Can we now add IL-36 to the list of inflammatory mediators that are not viable DMARD targets?

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?

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.

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?

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.

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.

Salivary gland ultrasonography is a promising tool for the evaluation of Sjögren's syndrome. Cumulative data suggest that ultrasonography is comparable with older imaging modalities such as sialography and scintigraphy. However, certain issues remain to be addressed before it can be integrated into current or future classification systems.