2. Academic Validation
  3. Anti-CD45RC antibody immunotherapy prevents and treats experimental autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome

Anti-CD45RC antibody immunotherapy prevents and treats experimental autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome

  • J Clin Invest. 2022 Apr 1;132(7):e156507. doi: 10.1172/JCI156507.
Marine Besnard 1,  Céline Sérazin 1,  Jason Ossart 1,  Anne Moreau 2,  Nadège Vimond 3,  Léa Flippe 1,  Hanna Sein 4,  Grace A Smith 5,  Stefania Pittaluga 5,  Elise Mn Ferré 6,  Claire Usal 1,  Ignacio Anegon 1,  Annamari Ranki 7,  Michail S Lionakis 6,  Pärt Peterson 4,  Carole Guillonneau 1
Affiliations

Affiliations

  • 1 Université de Nantes, Inserm, Centre de Recherche en Transplantation et Immunologie, UMR 1064, Institut de Transplantation Urologie-Néphrologie, Nantes, France.
  • 2 Anatomie et Cytologie Pathologiques, Centre Hospitalier Universitaire Nantes, Nantes, France.
  • 3 AbolerIS Pharma, Nantes, France.
  • 4 Molecular Pathology, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia.
  • 5 Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.
  • 6 Fungal Pathogenesis Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
  • 7 Department of Dermatology and Allergology, Clinicum, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
PMID: 35167497 DOI: 10.1172/JCI156507
Abstract

Targeted monoclonal antibody (mAb) therapies show great promise for the treatment of transplant rejection and autoimmune diseases by inducing more specific immunomodulatory effects than broadly immunosuppressive drugs routinely used. We recently described the therapeutic advantage of targeting CD45RC, expressed at high levels by conventional T (Tconv) cells (CD45RChi), their precursors, and terminally differentiated T (TEMRA) cells, but not by regulatory T cells (Tregs; CD45RClo/-). We demonstrated efficacy of anti-CD45RC mAb treatment in transplantation, but its potential has not been examined in autoimmune diseases. Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare genetic syndrome caused by loss-of-function mutations of autoimmune regulator (AIRE), a key central tolerance mediator, leading to abnormal autoreactive T cell responses and autoantibody production. Herein, we show that, in a rat model of APECED syndrome, anti-CD45RC mAb was effective for both prevention and treatment of autoimmune manifestations and inhibited autoantibody development. Anti-CD45RC mAb intervention depleted CD45RChi T cells, inhibited CD45RChi B cells, and restored the Treg/Tconv cell ratio and the altered Treg transcriptomic profile. In APECED patients, CD45RC was significantly increased in peripheral blood T cells, and lesioned organs from APECED patients were infiltrated by CD45RChi cells. Our observations highlight the potential role for CD45RChi cells in the pathogenesis of experimental and human APECED syndrome and the potential of anti-CD45RC antibody treatment.

Keywords

Autoimmune diseases; Autoimmunity; Immunotherapy; Therapeutics; Tolerance.

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