Immune signatures of prodromal multiple sclerosis in monozygotic twins

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.; Kuempfel, Tania; Wiendl, Heinz; Hohlfeld, Reinhard und Klotz, Luisa (2020): Immune signatures of prodromal multiple sclerosis in monozygotic twins. In: Proceedings of the National Academy of Sciences of the United States of America, Bd. 117, Nr. 35: S. 21546-21556

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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin > Munich Cluster for Systems Neurology (SyNergy)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0027-8424
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198