How does age determine the development of human immune-mediated arthritis?

Degboe, Y., Vastert, S. J., Prakken, B. J. and McInnes, I. B. (2022) How does age determine the development of human immune-mediated arthritis? Nature Reviews Rheumatology, 18(9), pp. 501-512. (doi: 10.1038/s41584-022-00814-3) (PMID:35948692) (PMCID:PMC9363867)

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Abstract

Does age substantially affect the emergence of human immune-mediated arthritis? Children do not usually develop immune-mediated articular inflammation during their first year of life. In patients with juvenile idiopathic arthritis, this apparent ‘immune privilege’ disintegrates, and chronic inflammation is associated with variable autoantibody signatures and patterns of disease that resemble adult arthritis phenotypes. Numerous mechanisms might be involved in this shift, including genetic and epigenetic predisposing factors, maturation of the immune system with a progressive modulation of putative tolerogenic controls, parallel development of microbial dysbiosis, accumulation of a pro-inflammatory burden driven by environmental exposures (the exposome) and comorbidity-related drivers. By exploring these mechanisms, we expand the discussion of three (not mutually exclusive) hypotheses on how these factors can contribute to the differences and similarities between the loss of immune tolerance in children and the development of established immune-mediated arthritis in adults. These three hypotheses relate to a critical window in genetics and epigenetics, immune maturation, and the accumulation of burden. The varied manifestation of the underlying mechanisms among individuals is only beginning to be clarified, but the establishment of a framework can facilitate the development of an integrated understanding of the pathogenesis of arthritis across all ages.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McInnes, Professor Iain and Degboe, Yannick
Authors: Degboe, Y., Vastert, S. J., Prakken, B. J., and McInnes, I. B.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Research Centre:College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Immunobiology
Journal Name:Nature Reviews Rheumatology
Publisher:Nature Research
ISSN:1759-4790
ISSN (Online):1759-4804
Published Online:10 August 2022

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