Reviews & Analysis

Primary immunodeficiency syndromes and autoimmune diseases seem to be different, but the clinical symptoms can be very similar. In this Review, the authors examine the causes and pathogenesis of several primary immunodeficiency syndromes and highlight their relationship to rheumatic diseases.

Connexins, hemichannels and gap junctions fulfil important functions in cell–cell communication. In this Review, the authors discuss the role of connexins, hemichannels and gap junctions in musculoskeletal tissues and rheumatic diseases.

Whether TNF inhibitors prevent structural damage in ankylosing spondylitis remains a controversial topic, as three prospective trials failed to show any evidence to support this notion. However, data are accumulating from retrospective analyses of well-characterized cohorts of patients that could provide the solution to this controversy.

This Review discusses the various functions of immunoregulatory semaphorins (known as immune semaphorins) and the role of these proteins in the pathogenesis of autoimmune rheumatic diseases, as well as their potential as diagnostic markers and therapeutic targets.

TNF inhibition is associated with an increased risk of lymphoma development. But is this association due to the TNF inhibitors themselves or the patient's underlying disease?

Primary and secondary failure of TNF antagonists can affect treatment strategies for rheumatoid arthritis. This article discusses the implications of immunogenicity, as well as methodological problems related to the detection of antidrug antibodies and trough drug levels.

This article provides an overview of the pathophysiology of enthesitis, from induction and inflammation to tissue proliferation and bone formation. Building on these pathophysiological concepts, the clinical presentation, assessment and treatment of enthesitis are also discussed.

The symptomatic pre-arthritis phase of rheumatoid arthritis (RA) is hypothesized to be part of a 'window of opportunity' for preventive treatment. This Review discusses the methodological considerations when designing and interpreting preventive trials, and translating findings into clinical practice.

In the past few years, excitement has grown over the potential use of mesenchymal stem cells (MSCs) for cartilage repair, although the rarity of these cells has hampered progress. In this Review, the authors examine the potential of joint-resident MSCs as a new avenue for repair in osteoarthritis.

Identifying different phenotypes of osteoarthritis is currently a subject of much research; however, a new systematic review has sparked discussion about the discrepancies in how research into disease phenotypes is conducted. Can we define individual phenotypes if we cannot agree on what constitutes a phenotype in the first place?

Biosimilar therapeutics for immune-mediated disease are approved in many countries and are increasingly being utilized in clinical practice. Although much has been written about the effectiveness and safety of biosimilars, less focus has been placed on why, how and when (or when not) to use these medications — until now.

Gout and osteoarthritis are known to coexist in certain joints, with urate and calcium crystals being associated with the development of osteoarthritis. Now, research is shedding light on the depth of this association and bringing surprising observations to the fore.

In this Review, the role of canonical Wnt signalling in articular cartilage is discussed, along with the regulatory mechanisms that exist to fine-tune Wnt signalling and the rationale for developing drugs that modulate Wnt signalling for the treatment of joint diseases such as osteoarthritis.

Symptoms associated with chronic inflammatory diseases such as fatigue, depression and muscle loss are often overlooked during treatment. This Perspectives article provides a framework for understanding many of these symptoms that is based on the concepts of evolutionary medicine, energy regulation and neuroendocrine–immune crosstalk.

Long non-coding RNAs (lncRNAs) are key regulators of gene expression. In this Review, the definition and function of lncRNAs, their importance in immune cell responses and the potential roles of these molecules in rheumatic diseases are discussed.

This Review explores the main mechanisms of inflammation and the role of innate immune sensors in gouty arthritis, and discusses potential therapeutic approaches aimed at regulating these processes.

For patients with osteoarthritis, the current palliative approach of analgesic prescription followed by joint replacement is often inappropriate. Instead, care should be tailored to the needs of individuals and targeted towards the central complaints of pain and functional limitation. So why are we still getting it wrong?

In this Consensus Statement, a group of experts propose that high-quality immunoassays, rather than indirect immunofluorescence, should be used as the primary screening method for detecting anti-neutrophil cytoplasmic antibodies when diagnosing patients with suspected granulomatosis with polyangiitis or microscopic polyangiitis.

Rapid progress in the fields of giant cell arteritis and polymyalgia rheumatica has resulted in the introduction of imaging techniques into routine clinical practice and in promising reports on the efficacy of biologic agents for treatment. Further research should further advance our understanding of the epidemiology, pathogenesis, imaging and treatment of these diseases.

Serum autoantibodies have a wide range of glycosylation patterns. In this Review, the authors describe the role of autoantibody glycosylation in the pathology of autoimmune disease, and how understanding the role of specific antibody glycoforms might optimize current treatment approaches.