Immune signatures of prodromal multiple sclerosis in monozygotic twins

Lisa Ann Gerdes, Claudia Janoschka, Maria Eveslage, Bianca Mannig, Timo Wirth, Andreas Schulte-Mecklenbeck, Sarah Lauks, Laura Glau, Catharina C. Gross, Eva Tolosa, Andrea Flierl-Hecht, Birgit Ertl-Wagner, Frederik Barkhof, Sven G. Meuth, Tania Kümpfel, Heinz Wiendl, Reinhard Hohlfeld, Luisa Klotz

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

The tremendous heterogeneity of the human population presents a major obstacle in understanding how autoimmune diseases like multiple sclerosis (MS) contribute to variations in human peripheral immune signatures. To minimize heterogeneity, we made use of a unique cohort of 43 monozygotic twin pairs clinically discordant for MS and searched for disease-related peripheral immune signatures in a systems biology approach covering a broad range of adaptive and innate immune populations on the protein level. Despite disease discordance, the immune signatures of MS-affected and unaffected cotwins were remarkably similar. Twinship alone contributed 56% of the immune variation, whereas MS explained 1 to 2% of the immune variance. Notably, distinct traits in CD4+ effector T cell subsets emerged when we focused on a subgroup of twins with signs of subclinical, prodromal MS in the clinically healthy cotwin. Some of these early-disease immune traits were confirmed in a second independent cohort of untreated early relapsing-remitting MS patients. Early involvement of effector T cell subsets thus points to a key role of T cells in MS disease initiation.
Original languageEnglish
Pages (from-to)21546-21556
Number of pages11
JournalProceedings of the National Academy of Sciences of the United States of America
Volume117
Issue number35
DOIs
Publication statusPublished - 1 Sep 2020

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