Immune signatures of prodromal multiple sclerosis in monozygotic twins

Author:

Gerdes Lisa AnnORCID,Janoschka Claudia,Eveslage MariaORCID,Mannig Bianca,Wirth Timo,Schulte-Mecklenbeck AndreasORCID,Lauks Sarah,Glau Laura,Gross Catharina C.,Tolosa Eva,Flierl-Hecht Andrea,Ertl-Wagner BirgitORCID,Barkhof FrederikORCID,Meuth Sven G.ORCID,Kümpfel TaniaORCID,Wiendl Heinz,Hohlfeld ReinhardORCID,Klotz Luisa

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.

Funder

Deutsche Forschungsgemeinschaft

Gemeinnuetzige Hertie Foundation

Bavarian association and national association of the German MS society

Dr. Leopold And Carmen Ellinger Foundation

Verein zur Therapieforschung fuer MS Kranke e.V.

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

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