Review Articles in 2018

Leukocytes travel through many different tissues during their lifetime, being educated by the cells and environments they encounter. An increased understanding of this journey in the context of rheumatoid arthritis offers hope for the development of future therapies.

A growing body of evidence indicates that neutrophils and neutrophil extracellular traps (NETs) are involved in the progression of rheumatic diseases. This Review focuses on the role of NETs in systemic lupus erythematosus, vasculitis, rheumatoid arthritis and gout.

The development of cartilage-penetrating therapies relies on an in-depth understanding of the biophysical properties of this complex tissue. In this Review, knowledge accumulated over 50 years is synthesized to reveal the key principles of solute transport in cartilage.

Vascular and obstetric antiphospholipid syndrome are associated with the same pathogenic antiphospholipid antibodies but differ with respect to their associated clinical manifestations. The expression and distribution of β2 glycoprotein I, the main target of antiphospholipid antibodies, might explain these differences.

Therapeutic application of cannabis remains controversial despite evidence of pain-relieving functions, particularly for rheumatic diseases. However, whether cannabis can also be used as an immunomodulatory therapeutic agent needs to be counterbalanced by risk assessment for adverse effects.

Endothelial dysfunction is thought to be an important contributor to the increased risk of cardiovascular diseases seen in patients with rheumatoid arthritis. Microvascular endothelial dysfunction could be a useful predictive marker of cardiovascular events in early rheumatoid arthritis.

Biomarkers are urgently needed to improve diagnosis and patient care in systemic sclerosis (SSc). Jimenez and colleagues discuss the current state of biomarkers for SSc and provide an update on how new biomarkers could make personalized medicine a reality.

The use of biomarkers for drug development, clinical investigation and management is fundamental to the success of molecular medicine. This Review discusses the framework for the development of biomarkers as drug development tools, including discovery, analytical validation, clinical qualification and utilization.

Axial disease occurs in psoriatic arthritis (PsA) and ankylosing spondylitis, but questions remain over whether axial PsA is a distinct disease. In this Review, the authors address the current state of knowledge concerning axial PsA and propose a research agenda.

In this Review, the authors summarize the results of genetics studies that confirm the importance of modulating urate levels in gout pathophysiology, and discuss how these discoveries could be applied to the treatment of hyperuricaemia and gout.

Multiple genetic and environmental factors contribute to the risk of developing idiopathic inflammatory myopathies; both immune and non-immune related mechanisms are involved in the pathogenesis of these disorders, the understanding of which might lead to novel treatment approaches.

Myositis-specific or myositis-associated antibodies can be found in most patients with myositis and are associated with distinct disease phenotypes. These antibodies also provide valuable insights into the pathogenesis of myositis and can help guide treatment.

Mitochondrial dysfunction and mitochondrial DNA (mtDNA) influence several molecular processes underlying the pathogenesis of osteoarthritis (OA), and mtDNA variants are associated with the development and progression of knee OA, pointing to a role for mtDNA variation in OA pathogenesis and its phenotypic presentation.

The idiopathic inflammatory myopathies are characterized by muscle weakness and inflammation. A range of tools are available to evaluate outcomes in the treatment of myositis, including, among others, core set measures that were developed by international networks of myositis researchers.

The idiopathic inflammatory myopathies are a group of disorders that involve inflammation of skeletal muscles and extramuscular manifestations. New classification criteria capture a broad range of these disorders but should be further defined in the future to incorporate new data.

Many immunosuppressive and immunomodulatory therapies are available to clinicians for managing myositis, and numerous biologic and small-molecule therapies are emerging that target implicated pathogenic targets. However, care must be taken when considering the numerous extramuscular complications of this disease.

Space travel induces bone loss in crewmembers, who often develop signs of accelerated bone ageing. Here, Vico and Hargens describe the effects of space travel on the skeleton and explain how these findings can inform research into ageing and immobility.

Platelets mediate many non-haemostatic responses, including immune responses, through the production or release of various mediators. Platelets are activated in systemic lupus erythematosus and are implicated in its pathogenesis, and present opportunities for therapeutic intervention.

Inappropriate activation of the type I interferon pathway is implicated in the pathogenesis of multiple rheumatic diseases. Variation in type I interferon activity between patients is revealing new information about pathogenesis and treatment responses that could aid personalization of therapy.

The presence of anti-citrullinated protein antibodies (ACPAs) is a useful biomarker in rheumatoid arthritis (RA). New technological advances are helping to unravel the role of the anti-citrullinated antigen response in RA pathogenesis, in particular, the contribution of ACPAs, ACPA glycosylation and ACPA-expressing B cells.