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Induction of immune tolerance in the treatment of rheumatoid arthritis

Nature Reviews Rheumatology volume 7, pages 272–281 (2011)Cite this article

Subjects

Abstract

Progress in our understanding of the genetics and immunology of rheumatoid arthritis (RA) has translated into clinical practice with the introduction of a first generation of biologic agents that effectively interfere with the inflammatory cascade by blocking a key component. This evolution has not only changed the way we practice, but perhaps also the way we think about RA and its treatment. In our view direct manipulation of specific pathogenic pathways is increasingly being used to replace generalized pharmacological immune suppression. The next leap forward will be to develop therapeutic approaches that will lead to maintenance of disease remission with a minimal-treatment or even drug-free regimen, relying on the induction of immune tolerance rather than the suppression of the immune system. Immune tolerance has the potential to prevent tissue damage secondary to inflammatory responses while at the same time maintaining homeostasis through physiologic recognition of self and the ability to perceive and react to 'danger'. Novel therapeutic approaches are emerging from these concepts. Such therapies will hopefully be safe and efficacious, and will complement the first generation of biologic agents that are currently available.

Key Points

  • Immune tolerance is the process by which the immune system recognizes but does not attack the body's own antigens; this mechanism is impaired in autoimmune disorders

  • Restoring a state of immune tolerance could help to achieve the goal of maintaining disease remission with a minimal-treatment regimen

  • Several antigen-independent as well as antigen-dependent strategies to induce tolerance in patients with rheumatoid arthritis (RA) are under development

  • Biologic agents seem to have effects that go beyond their original target and could induce antigen-independent immune tolerance

  • Second generation antigen-specific immunotherapeutic approaches that focus on epitopes involved in disease pathogenesis, such as those from heat shock proteins, have shown some promise in RA treatment

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Figure 1: Targets of immune tolerance induction.
Figure 2: Heat shock proteins as a target of trigger-independent antigen-specific therapy.
Figure 3: Tolerance induction as a 'work-with' approach.

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Acknowledgements

S. Albani is supported by NIH Grants and the Bartman Foundation. B. Prakken is supported by the Dutch Rheumatoid Arthritis Foundation and grants from the Dutch Organization for Scientific Research and the 5th European Framework Grant 'HSP for therapy'. E. C. Koffeman is supported by the Ter Meulen Fonds from the Royal Netherlands Academy of Sciences. The authors would like to acknowledge Jessica Colomb's contribution to the preparation of this manuscript.

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Authors and Affiliations

  1. Translational Research Program, Inflammatory and Infectious Diseases Center, Sanford-Burnham Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, 92037, CA, USA

    Salvatore Albani

  2. Department of Pediatric Immunology, Center for Molecular and Cellular Intervention, University Medical Center Utrecht, PO Box 85090, Utrecht, 3508 AB, The Netherlands

    Eva C. Koffeman & Berent Prakken

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S. Albani, E. C. Koffeman and B. Prakken contributed equally to researching the data for the article and to the review and/or editing of the manuscript before submission. S. Albani and B. Prakken contributed to discussions of the content and writing the article.

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Correspondence to Salvatore Albani.

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S. Albani is a patent holder/applicant for a University of California, San Diego product. The other authors declare no competing interests.

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Albani, S., Koffeman, E. & Prakken, B. Induction of immune tolerance in the treatment of rheumatoid arthritis. Nat Rev Rheumatol 7, 272–281 (2011). https://doi.org/10.1038/nrrheum.2011.36

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