Review Articles in 2021

Most rheumatic and musculoskeletal diseases (RMDs) fall along a spectrum of disorders from autoinflammatory diseases to autoimmune diseases, with ‘mixed-pattern’ RMDs having features of autoinflammation and autoimmunity. A better understanding of the pathogenic pathways of autoinflammation and autoimmunity in RMDs should enhance targeted treatment strategies.

Hypertension and osteoarthritis are associated with each other epidemiologically and share several molecular pathways. In this Review, the authors examine the crossover between these two conditions and propose the repurposing of antihypertensive medications to treat osteoarthritis.

Physical function is an important contributor towards a patient’s quality of life, but is often neglected in management strategies for axial spondyloarthritis (axSpA). This Review provides guidance on determinants and assessments of physical function in axSpA.

Lyme arthritis, a manifestation of Lyme disease, can sometimes persist in a chronic post-infectious disease. In this Review, the authors argue that post-infectious Lyme arthritis could act as a model to improve understanding of other forms of chronic arthritis.

Tumour necrosis factor (TNF) inhibitors are effective treatments for autoimmune and rheumatic diseases. Here, Salomon reviews the complex pro-inflammatory and regulatory roles of TNF, highlighting its effects on the expansion, differentiation and suppressive function of regulatory T cells and their implications for the design of future anti-TNF agents.

Genome editing technology, such as CRISPR–Cas, has great potential in the study of rheumatic disease genetics, including in discovering disease-associated genes and regulatory regions, in validating causal variants and in characterizing important cell types and cell states.

Advances in understanding the pathogenic mechanisms of primary Sjögren syndrome (pSS) and the development of new outcome measures are aiding drug development for this disease. This Review describes current treatments and highlights promising candidates for future therapies for pSS.

Ankylosing spondylitis (AS) is a chronic inflammatory disease with hallmarks of both autoimmune and autoinflammatory pathology. In this Review, the authors examine the evidence for both disease processes and aim to reconcile the two.

The intervertebral disc (IVD) is a hypoxic environment, and the hypoxia-inducible factor (HIF) family of transcription factors enable cells of the disc to adapt to these conditions. Understanding HIF-related mechanisms could help in the generation of therapies for IVD degeneration.

Monogenic autoinflammatory diseases are linked to various germline and somatic pathogenic variants but numerous factors must be considered to explain their large phenotypic variability. This Review discusses genotype–phenotype relationships and the potential molecular mechanisms that might explain this variability.

Salivary gland dysfunction is an important characteristic of primary Sjögren syndrome (pSS). In this Review, the authors discuss various epithelial abnormalities in pSS and the mechanisms by which epithelial cell–immune cell interactions contribute to disease development and progression.

Type III interferons (IFNλs) affect innate and adaptive immune responses and are associated with the pathogenesis of autoimmune rheumatic diseases. In this Review, the authors provide an overview of IFNλs in rheumatic diseases and discuss therapeutic strategies to target them.

Immune-related disorders in patients with COVID-19 are increasingly being reported worldwide, with thousands of cases recorded of manifestations that can mimic a broad range of systemic and organ-specific inflammatory and autoimmune diseases.

The prevalence of rheumatic diseases is increasing in African countries, leading to an increased need for specialist rheumatologists and disease-modifying drugs. In this Review, the authors outline what is currently known about the state of rheumatic diseases in Africa.

Various drugs used in rheumatoid arthritis management have anti-inflammatory effects that can hinder atherosclerosis development and progression. However, these drugs can also concurrently have different pro-atherogenic effects, complicating the relationship between these drugs and cardiovascular involvement in rheumatoid arthritis.

Pathogenic, long-lived memory cells of the immune system present a barrier to resolution of chronic inflammatory rheumatic diseases. Approaches to selectively eliminate these cells while sparing protective immune memory cells could restore immunological tolerance and achieve treatment-free remission.

Childhood-onset arthritis has historically been treated as a separate entity to adult-onset arthritis, with its own nomenclature and classification system. Biological evidence has revealed the limitations of the current approach, necessitating a fresh look at the classification of paediatric arthritis.

TNF inhibitors are used to treat various immune-related adverse events caused by immune checkpoint inhibitors (ICIs). However, whether TNF inhibition compromises the anticancer efficacy of ICI therapy is unknown. This Review discusses the relationship between TNF, TNF inhibition and cancer.

Intestinal dysbiosis is thought to be involved in the early stages of rheumatoid arthritis (RA). In this Review, the authors discuss the gut–joint axis in RA and the potentially pathogenic role of gut-derived immune cells in the joints.

In this Review, the authors discuss macrophage activation syndrome (MAS) in relation to other cytokine storm scenarios, and provide a framework for understanding MAS within the spectrum of innate and adaptive immunity in the context of gain or loss of immune function.