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CTLA4 as Immunological Checkpoint in the Development of Multiple Sclerosis |
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| Authors: | Lisa Ann Gerdes MD Kathrin Held PhD Eduardo Beltrán PhD Carola Berking MD Jörg C. Prinz MD Andreas Junker MD Julia K. Tietze MD Birgit Ertl‐Wagner MD Andreas Straube MD Tania Kümpfel MD Klaus Dornmair PhD Reinhard Hohlfeld MD |
| Affiliation: | 1. Institute of Clinical Neuroimmunology, Biomedical Center and University Hospital, Grosshadern‐Martinsried Campus, Ludwig Maximilian University, Munich;2. Department of Dermatology and Allergology, Ludwig Maximilian University, Munich;3. Department of Neuropathology, University of G?ttingen, G?ttingen;4. Department of Neuropathology, University of Duisburg‐Essen, Essen;5. Department of Radiology, Grosshadern Medical Campus, Ludwig Maximilian University, Munich;6. Department of Neurology, Ludwig Maximilian University, Munich;7. Munich Cluster of Systems Neurology (SyNergy), Munich, Germany |
| Abstract: | 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 |
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