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Re-establishing tolerance to autoantigens is an important aim for the treatment of rheumatoid arthritis (RA). Immunization of HLA-DR4 transgenic mice with citrullinated self-antigens can induce immune tolerance, which suggests that such antigens could have a therapeutic role in anti-citrullinated peptide antibody-positive RA.
This Review explores the potential of emerging RNA-based technologies and cell-engineering strategies, including those that incorporate small interfering RNA, microRNA, mRNA and synthetic receptor-mediated gene editing, to provide innovative and targeted approaches to osteoarthritis therapy.
The identification of novel risk variants in the largest genome-wide association study of Raynaud phenomenon to date provides insights into the pathophysiology of the condition, including the potential role for α2A-adrenoceptors, and suggests opportunities for drug repurposing.
New research has shown that tryptophan metabolism is altered in patients with rheumatoid arthritis, and that correction of this metabolic alteration has a protective effect against collagen-antibody-induced arthritis in mice.
Janus kinase inhibitors have therapeutic potential for patients with immune-mediated inflammatory diseases, and evidence of greater risks of cardiovascular disease and malignancy than with TNF inhibitors should be carefully considered before recommendations against their use are made. Assessment of the risk–benefit ratios in these patients can instead guide clinical decision-making.
Concerns have been raised about the safety of Janus kinase (JAK) inhibitors. This Review summarizes the evidence regarding the risks and benefits of JAK inhibitors to clarify which patients are most at risk of adverse events and guide clinical decision-making.
In patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis in sustained remission, reinfusion with rituximab after B cell repopulation resulted in fewer clinical relapses than did reinfusion following serological ANCA flare.
In this Review, the authors describe shared pathophysiology of systemic juvenile idiopathic arthritis and adult-onset Still’s disease and their life-threatening complication, macrophage activation syndrome. Therapeutic developments now enable the targeting of multiple pathways in these conditions, and evidence suggests that early use of DMARDs has the potential to prevent chronic disease.
Studies published in 2023 emphasize the long-term efficacy and safety of novel therapeutics for both radiographic and non-radiographic axial spondyloarthritis (axSpA) and provide a consensus definition of ‘early axSpA’ for use in research studies.
Advances in gene, protein and cellular engineering provide unprecedented opportunities to redirect immune cells to treat autoimmunity. In 2023, novel cellular and precision immunotherapies showed remarkable promise in the treatment of rheumatic diseases.
Research published in 2023 has demonstrated the efficacy of sarilumab for IL-6 blockade in polymyalgia rheumatica and of secukinumab for IL-17 blockade in giant cell arteritis (GCA). Furthermore, preliminary results with human monocyte-derived suppressive cells suggest the potential of cellular therapeutics for the treatment of GCA.
In 2023, large language models demonstrated potential for use in rheumatology to accurately suggest diagnoses and provide empathetic patient education. However, the propensity of this technology to generate misleading information continues to pose risks. Balancing innovation with physician guidance is essential.
In this epidemiological Review, the authors summarize the available evidence relating to the prevalence, incidence, risk factors and mortality associated with the autoimmune disorder Sjögren syndrome, with or without the co-occurrence of other connective tissue diseases.
For individuals with gout, the treatment options beyond conventional urate-lowering therapies are expanding. Notable advancements in 2023 include developments in uricase therapy, new xanthine oxidase inhibitors, and a class of medications that offer dual benefits for the control of type 2 diabetes mellitus and gout.
Studies in 2023 have described eight new monogenic autoinflammatory diseases and their accompanying disease-causing mutations, uncovering clinical phenotypes, pathogenic mechanisms and therapeutic targets. Researchers have identified autoinflammatory pathways linked to mitochondrial dysfunction or overactivation of SRC family kinases.
In this Review, the authors discuss the role of IL-18 in human inflammatory disease. They describe the mechanisms of IL-18 biology, discuss how dysregulation of this biology leads to immunopathology, and note the biological and clinical circumstances in which therapeutic manipulation might alleviate suffering and save lives.
A novel combination of ceria nanoparticles and mesenchymal stem cell nanovesicles modified both inflammation and autoimmunity in a mouse model of arthritis.
In this Review, the authors provide an overview of what is known of the clinical features, pathogenesis and treatment of anti-melanoma differentiation-associated protein 5 antibody-positive dermatomyositis, including emerging biomarkers and clinical subtypes.
