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Tolerance-inducing medicines in autoimmunity: rheumatology and beyond

Lookup NU author(s): Dr James Stanway, Professor John IsaacsORCiD


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© 2020 Elsevier LtdAutoimmunity is currently managed with generalised immunosuppression, which is associated with serious side-effects such as infection and cancer. An ideal treatment strategy would be to induce immune tolerance—ie, to reprogramme the immune system to stop recognising the host itself as a threat. Drug-free remission should follow such an intervention, representing a change in the approach to the treatment of autoimmune disease. Tolerance induction is achievable in animal models of autoimmunity but translation to the clinic has been slow. Nonetheless, progress has been made—eg, restoration of therapeutic responsiveness and drug-free remission have been achieved with stem cell transplantation in refractory autoimmunity, and significant delays in onset of type 1 diabetes in individuals at high risk have been achieved following a brief treatment with anti-CD3 monoclonal antibody. In the future, antigen-specific interventions should provide highly targeted, personalised approaches, avoiding generalised immunosuppression entirely. Such trials have already started, using both direct autoantigenic peptide administration, cellular therapies, and other modalities. In this Series paper, we discuss the history of immune tolerance induction with a focus on rheumatological disease while also highlighting essential data from other specialties. We propose key unanswered questions, which will be covered in other papers in this Series.

Publication metadata

Author(s): Stanway JA, Isaacs JD

Publication type: Review

Publication status: Published

Journal: The Lancet Rheumatology

Year: 2020

Volume: 2

Issue: 9

Pages: e565-e575

Print publication date: 01/09/2020

Online publication date: 26/08/2020

Acceptance date: 02/04/2016

ISSN (electronic): 2665-9913

Publisher: Lancet Publishing Group


DOI: 10.1016/S2665-9913(20)30100-4