Preclinical models of arthritis for studying immunotherapy and immune tolerance

Meehan, G. R. et al. (2021) Preclinical models of arthritis for studying immunotherapy and immune tolerance. Annals of the Rheumatic Diseases, 80(10), pp. 1268-1277. (doi: 10.1136/annrheumdis-2021-220043) (PMID:34380700)

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Increasingly earlier identification of individuals at high risk of rheumatoid arthritis (RA) (eg, with autoantibodies and mild symptoms) improves the feasibility of preventing or curing disease. The use of antigen-specific immunotherapies to reinstate immunological self-tolerance represent a highly attractive strategy due to their potential to induce disease resolution, in contrast to existing approaches that require long-term treatment of underlying symptoms. Preclinical animal models have been used to understand disease mechanisms and to evaluate novel immunotherapeutic approaches. However, models are required to understand critical processes supporting disease development such as the breach of self-tolerance that triggers autoimmunity and the progression from asymptomatic autoimmunity to joint pain and bone loss. These models would also be useful in evaluating the response to treatment in the pre-RA period. This review proposes that focusing on immune processes contributing to initial disease induction rather than end-stage pathological consequences is essential to allow development and evaluation of novel immunotherapies for early intervention. We will describe and critique existing models in arthritis and the broader field of autoimmunity that may fulfil these criteria. We will also identify key gaps in our ability to study these processes in animal models, to highlight where further research should be targeted.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Hilkens, Dr Catharien and Brewer, Professor James and Garside, Professor Paul and Meehan, Dr Gavin and Al Khabouri, Shaima Mazin Jawad
Authors: Meehan, G. R., Thomas, R., Al Khabouri, S., Wehr, P., Hilkens, C. M.U., Wraith, D. C., Sieghart, D., Bonelli, M., Nagy, G., Garside, P., Tough, D. F., Lewis, H. D., and Brewer, J. M.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
Journal Name:Annals of the Rheumatic Diseases
Publisher:BMJ Publishing Group
ISSN (Online):0003-4967
Published Online:11 August 2021
Copyright Holders:Copyright © 2021 The Authors
First Published:First published in Annals of the Rheumatic Diseases 80(10): 1268-1277
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
301069Rheuma Tolerance for CureIain McInnesEuropean Commission (EC)777357III - Immunology