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; Straube, Andreas; Kümpfel, Tania; Dornmair, Klaus und Hohlfeld, Reinhard (2016): CTLA4 as Immunological Checkpoint in the Development of Multiple Sclerosis. In: Annals of Neurology, Bd. 80, Nr. 2: S. 294-300

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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0364-5134
• Sprache: Englisch