1. Immune signatures of prodromal multiple sclerosis in monozygotic twins.
- Author
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Gerdes, Lisa Ann, Janoschka, Claudia, Eveslage, Maria, Mannig, Bianca, Wirth, Timo, Schulte-Mecklenbeck, Andreas, Lauks, Sarah, Glau, Laura, Gross, Catharina C., Tolosa, Eva, Flierl-Hecht, Andrea, Ertl-Wagner, Birgit, Barkhof, Frederik, Meuth, Sven G., Kümpfel, Tania, Wiendl, Heinz, Hohlfeld, Reinhard, and Klotz, Luisa
- Subjects
TWINS ,MULTIPLE sclerosis ,POPULATION ,T cells ,SYSTEMS biology - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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