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Preclinical models of arthritis for studying immunotherapy and immune tolerance

Lookup NU author(s): Dr Catharien Hilkens, Professor Paul Garside

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

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.


Publication metadata

Author(s): Meehan G, Thomas R, Khabouri S, Wehr P, Hilkens CM, Wraith DC, Sieghart D, Bonelli M, Nagy G, Garside P, Tough DF, Lewis HD, Brewer JM

Publication type: Review

Publication status: Published

Journal: Annals of the Rheumatic Diseases

Year: 2021

Pages: Epub ahead of print

Online publication date: 11/08/2021

Acceptance date: 27/06/2021

ISSN (print): 0003-4967

ISSN (electronic): 1468-2060

URL: https://doi.org/10.1136/annrheumdis-2021-220043

DOI: 10.1136/annrheumdis-2021-220043


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