CTLA-4 as immunological checkpoint in the development of multiple sclerosis
Annals of Neurology. 2016 June 28. DOI: 10.1002/ana.24715. [Epub ahead of print]
|Authors/Editors:||Gerdes L A, Held K, Beltran E, Berking C, Prinz J C, Junker A, Tietze J K, Ertl-Wagner B, Straube A, Kümpfel T, Dornmair K, Hohlfeld R|
We investigated a patient who developed multiple sclerosis (MS) during treatment with the CTLA-4-blocking antibody ipilimumab for metastatic melanoma. Initially he showed subclinical MRI changes (“radiologically isolated syndrome”). Two courses of ipilimumab were each followed by a clinical episode of MS, one 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 CSF. Our results pinpoint the co-inhibitory molecule CTLA-4 as an immunological checkpoint and therapeutic target in MS.