REVIEW article
Front. Immunol.
Sec. Autoimmune and Autoinflammatory Disorders: Autoinflammatory Disorders
Citrullinated Peptides as Drug Candidates for Rheumatoid Arthritis
Provisionally accepted
- 1Danmarks Tekniske Universitet, Lyngby, Denmark
- 2Aarhus Universitet, Aarhus, Denmark
- 3Aarhus Universitetshospital Molekylaer Medicinsk afdeling, Aarhus, Denmark
- 4Regionshospitalet Silkeborg, Silkeborg, Denmark
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Rheumatoid arthritis (RA) involves a breakdown of immune tolerance to citrullinated proteins, leading to chronic inflammation and joint damage. Despite advances in treatment, achieving long-term remission remains a major challenge. Restoring immune tolerance to citrullinated proteins represents a promising strategy to halt disease progression and establish lasting remission. This review examines the potential of using citrullinated proteins or peptides to reestablish immune tolerance in RA. It explores the potential role of anti-citrullinated protein antibodies (ACPAs) in disease pathology and how utilizing or targeting specific citrullinated antigens could modulate immune responses. The review also highlights the therapeutic relevance of altering T and B cell function to regulate immune state. We explore mechanisms through which tolerance can be induced, including the use of citrullinated peptides to promote regulatory T (Treg) cell expansion and alter pathogenic B cell subsets. Emerging strategies aimed at re-educating the immune system are discussed, focusing on their potential to provide effective and durable treatment outcomes. These tolerance-based approaches are evaluated for their capacity to shift the immune response away from autoimmunity and towards sustained remission.
Keywords: Rheumatoid arthritis, citrullinated peptides, tolerance recovery, anti-citrullinatedprotein antibodies, antigen-specific therapy
Received: 17 Jun 2025; Accepted: 05 Nov 2025.
Copyright: © 2025 H Bustos, Brüner, Kragstrup and Astakhova. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Kira Astakhova, kiraas@kemi.dtu.dk
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