CTLA4 as Immunological Checkpoint in the Development of Multiple Sclerosis

• Published in: Annals of neurology Vol. 80; no. 2; pp. 294 - 300
• Main Authors: Gerdes, Lisa Ann, Held, Kathrin, Beltrán, Eduardo, Berking, Carola, Prinz, Jörg C., Junker, Andreas, Tietze, Julia K., Ertl-Wagner, Birgit, Straube, Andreas, Kümpfel, Tania, Dornmair, Klaus, Hohlfeld, Reinhard
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.08.2016; Wiley Subscription Services, Inc; John Wiley and Sons Inc
• Subjects: Adult; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal - therapeutic use; Brief Communication; Brief Communications; CD4-Positive T-Lymphocytes - drug effects; CD8-Positive T-Lymphocytes - drug effects; Cerebrospinal Fluid - cytology; CTLA-4 Antigen - immunology; Humans; Immunology; Ipilimumab; Male; Melanoma; Melanoma - cerebrospinal fluid; Melanoma - drug therapy; Melanoma - immunology; Multiple sclerosis; Multiple Sclerosis - cerebrospinal fluid; Multiple Sclerosis - chemically induced; Multiple Sclerosis - immunology; NMR; Nuclear magnetic resonance; T cell receptors
• ISSN: 0364-5134; 1531-8249; 1531-8249
• DOI: 10.1002/ana.24715

We investigated a patient who developed multiple sclerosis (MS) during treatment with the CTLA4‐blocking antibody ipilimumab for metastatic melanoma. Initially he showed subclinical magnetic resonance imaging (MRI) changes (radiologically isolated syndrome). Two courses of ipilimumab were each followed by a clinical episode of MS, 1 of which was accompanied by a massive increase of MRI activity. Brain biopsy confirmed active, T‐cell type MS. Quantitative next generation sequencing of T‐cell receptor genes revealed distinct oligoclonal CD4+ and CD8+ T‐cell repertoires in the primary melanoma and cerebrospinal fluid. Our results pinpoint the coinhibitory molecule CTLA4 as an immunological checkpoint and therapeutic target in MS. Ann Neurol 2016;80:294–300