Immune signatures of prodromal multiple sclerosis in monozygotic twins.
Proc Natl Acad Sci U S A. 2020;202003339. doi:10.1073/pnas.2003339117 [published online ahead of print, 2020 Aug 17]
| Authors/Editors: | Gerdes LA, Janoschka C, Eveslage M, Mannig B, Wirth T, Schulte-Mecklenbeck A, Lauks S, Glau L, Gross CC, Tolosa E, Flierl-Hecht A, Ertl-Wagner B, Barkhof F, Meuth SG, Kümpfel T, Wiendl H, Hohlfeld R, Klotz L. |
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| Publication Date: | 2020 |
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.
