Preclinical models of arthritis for studying immunotherapy and immune tolerance

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.

EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update

“…Therapy with DMARDs should be started as soon as the diagnosis of RA is made. In light of recent debates about definitions of pre-RA, [20][21][22] the question arose whether the term 'diagnosis of RA' is limited to patients with the full picture of the disease or also includes 'suspected' RA. However, the majority of the participants felt that 'suspected RA' is a field of research with too many uncertainties; that the whole evidence base of RA-treatment rests on a diagnosis (observational studies) or classification of RA (randomised controlled trials, RCTs); and that therefore the management of RA should pertain to those in whom a compelling clinical diagnosis of RA (not necessarily the full classical picture of RA, that we nowadays rarely see) has been made.…”

Functional Analysis of Autoantibody Signatures in Rheumatoid Arthritis

“…In the search for improved and novel therapeutics for RA, animal models play a major role in research and development. In a recent review, Meehan et al described the currently available collection of preclinical models [6]. Besides the known advantages and limitations of these models, currently no comparative analysis of auto-antibody signatures for RA and its respective animal models can be found within the literature.…”

Remodeling articular immune homeostasis with an efferocytosis-informed nanoimitator mitigates rheumatoid arthritis in mice

“…A collagen-induced arthritis (CIA) mouse model based on DBA/1 J mice was first established as previously reported 27 , 28 . The in vivo biodistribution and pharmacokinetic properties of the self-deliverable nanoimitator were next evaluated.…”