CTLA4 as Immunological Checkpoint in the Development of Multiple Sclerosis.

Gerdes, Lisa Ann; Held, Kathrin; Beltrán, Eduardo; Berking, Carola; Prinz, Jörg C; Junker, Andreas; Tietze, Julia K; Ertl-Wagner, Birgit et al. · Ann Neurol · 2016

case_report · Level V

Where this comes from

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.

Medical subject headings