CTLA4 as Immunological Checkpoint in the Development of Multiple Sclerosis

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 follo...

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Autores principales: 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, Hohlfeld, Reinhard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2016
Materias:
Brief Communications
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5129566/
https://www.ncbi.nlm.nih.gov/pubmed/27351142
http://dx.doi.org/10.1002/ana.24715
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author 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
Hohlfeld, Reinhard
author_facet 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
Hohlfeld, Reinhard
author_sort Gerdes, Lisa Ann
collection PubMed
description 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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spelling pubmed-51295662016-11-30 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 Hohlfeld, Reinhard Ann Neurol Brief Communications 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 John Wiley and Sons Inc. 2016-07-15 2016-08 /pmc/articles/PMC5129566/ /pubmed/27351142 http://dx.doi.org/10.1002/ana.24715 Text en © 2016 The Authors. Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs (http://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Brief Communications
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
Hohlfeld, Reinhard
CTLA4 as Immunological Checkpoint in the Development of Multiple Sclerosis
title CTLA4 as Immunological Checkpoint in the Development of Multiple Sclerosis
title_full CTLA4 as Immunological Checkpoint in the Development of Multiple Sclerosis
title_fullStr CTLA4 as Immunological Checkpoint in the Development of Multiple Sclerosis
title_full_unstemmed CTLA4 as Immunological Checkpoint in the Development of Multiple Sclerosis
title_short CTLA4 as Immunological Checkpoint in the Development of Multiple Sclerosis
title_sort ctla4 as immunological checkpoint in the development of multiple sclerosis
topic Brief Communications
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5129566/
https://www.ncbi.nlm.nih.gov/pubmed/27351142
http://dx.doi.org/10.1002/ana.24715
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