Review Articles

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  • 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.

    • Yuriy Baglaenko
    • Dana Macfarlane
    • Soumya Raychaudhuri
    Review Article
  • 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.

    • Raphaèle Seror
    • Gaetane Nocturne
    • Xavier Mariette
    Review Article
  • 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.

    • Daniele Mauro
    • Ranjeny Thomas
    • Francesco Ciccia
    Review Article
  • 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.

    • Elizabeth S. Silagi
    • Ernestina Schipani
    • Makarand V. Risbud
    Review Article
  • 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.

    • Ivona Aksentijevich
    • Oskar Schnappauf
    Review Article
  • 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.

    • Gwenny M. Verstappen
    • Sarah Pringle
    • Frans G. M. Kroese
    Review Article
  • 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.

    • Rishi R. Goel
    • Sergei V. Kotenko
    • Mariana J. Kaplan
    Review Article
  • 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.

    • Manuel Ramos-Casals
    • Pilar Brito-Zerón
    • Xavier Mariette
    Review Article
  • 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.

    • Olufemi Adelowo
    • Girish M. Mody
    • Samy Slimani
    Review Article
  • 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.

    • Fabiola Atzeni
    • Javier Rodríguez-Carrio
    • Zoltán Szekanecz
    Review Article
  • 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.

    • Patrick Maschmeyer
    • Hyun-Dong Chang
    • Andreas Radbruch
    Review Article
  • 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.

    • Peter A. Nigrovic
    • Robert A. Colbert
    • Alberto Martini
    Review Article
  • 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.

    • Allen Y. Chen
    • Jedd D. Wolchok
    • Anne R. Bass
    Review Article
  • 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.

    • Mario M. Zaiss
    • Hsin-Jung Joyce Wu
    • Francesco Ciccia
    Review Article
  • 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.

    • Dennis McGonagle
    • Athimalaipet V. Ramanan
    • Charlie Bridgewood
    Review Article
  • Intervertebral disc (IVD) degeneration is a common condition associated with low back pain, but approved pharmacological interventions to prevent progression of IVD degeneration are lacking. This Review discusses the clinical progress and challenges of cell-based therapeutics for repairing the IVD.

    • Abbie L. A. Binch
    • Joan C. Fitzgerald
    • Frank Barry
    Review Article
  • In this Review, the authors examine how the definition and description of axial spondyloarthritis (axSpA) has evolved, most notably with the introduction of the concept of non-radiographic axSpA, and discuss the implications of these changes for diagnosis, classification and therapy.

    • Philip C. Robinson
    • Sjef van der Linden
    • William J. Taylor
    Review Article
  • Loss of B cell tolerance to autoantigens in systemic lupus erythematosus (SLE) is driven by TLR7, whereas TLR9 appears to protect against SLE by limiting the stimulatory activity of TLR7. The unique features of Toll-like receptor signalling in B cells implicate it as a therapeutic target in SLE.

    • Simon Fillatreau
    • Benoît Manfroi
    • Thomas Dörner
    Review Article
  • The immunogenicity of a biologic agent can have clinical consequences in terms of response to therapy and risk of adverse events. In this Review, the authors summarize the latest data on the immunogenicity of biologic agents for various rheumatic indications.

    • Vibeke Strand
    • Joao Goncalves
    • John D. Isaacs
    Review Article