title: CTLA4 as Immunological Checkpoint in the Development of Multiple Sclerosis.
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.
authors.affiliation: Institute of Clinical Neuroimmunology, Biomedical Center and University Hospital, Grosshadern-Martinsried Campus, Ludwig Maximilian University, Munich.
authors.forename: Lisa Ann
authors.identifier: http://orcid.org/0000-0002-7053-3924
authors.initials: LA
authors.lastname: Gerdes
authors.affiliation: Institute of Clinical Neuroimmunology, Biomedical Center and University Hospital, Grosshadern-Martinsried Campus, Ludwig Maximilian University, Munich.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Held
authors.affiliation: Institute of Clinical Neuroimmunology, Biomedical Center and University Hospital, Grosshadern-Martinsried Campus, Ludwig Maximilian University, Munich.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Beltrán
authors.affiliation: Department of Dermatology and Allergology, Ludwig Maximilian University, Munich.
authors.forename: Carola
authors.initials: C
authors.lastname: Berking
authors.affiliation: Department of Dermatology and Allergology, Ludwig Maximilian University, Munich.
authors.forename: Jörg C
authors.initials: JC
authors.lastname: Prinz
authors.affiliation: Department of Neuropathology, University of Göttingen, Göttingen.|Department of Neuropathology, University of Duisburg-Essen, Essen.
authors.forename: Andreas
authors.initials: A
authors.lastname: Junker
authors.affiliation: Department of Dermatology and Allergology, Ludwig Maximilian University, Munich.
authors.forename: Julia K
authors.initials: JK
authors.lastname: Tietze
authors.affiliation: Department of Radiology, Grosshadern Medical Campus, Ludwig Maximilian University, Munich.
authors.forename: Birgit
authors.initials: B
authors.lastname: Ertl-Wagner
authors.affiliation: Department of Neurology, Ludwig Maximilian University, Munich.
authors.forename: Andreas
authors.initials: A
authors.lastname: Straube
authors.affiliation: Institute of Clinical Neuroimmunology, Biomedical Center and University Hospital, Grosshadern-Martinsried Campus, Ludwig Maximilian University, Munich.
authors.forename: Tania
authors.initials: T
authors.lastname: Kümpfel
authors.affiliation: Institute of Clinical Neuroimmunology, Biomedical Center and University Hospital, Grosshadern-Martinsried Campus, Ludwig Maximilian University, Munich.
authors.forename: Klaus
authors.initials: K
authors.lastname: Dornmair
authors.affiliation: Institute of Clinical Neuroimmunology, Biomedical Center and University Hospital, Grosshadern-Martinsried Campus, Ludwig Maximilian University, Munich.|Munich Cluster of Systems Neurology (SyNergy), Munich, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Hohlfeld
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects; D060908:CTLA-4 Antigen / Q000276:immunology*; D002555:Cerebrospinal Fluid / Q000166:cytology; D006801:Humans; D000074324:Ipilimumab; D008297:Male; D008545:Melanoma / Q000134:cerebrospinal fluid / Q000188:drug therapy / Q000276:immunology; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid / Q000139:chemically induced / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D000074324:Ipilimumab