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Immune signatures of prodromal multiple sclerosis in monozygotic twins

Gerdes, LA; Janoschka, C; Eveslage, M; Mannig, B; Wirth, T; Schulte-Mecklenbeck, A; Lauks, S; ... Klotz, L; + view all (2020) Immune signatures of prodromal multiple sclerosis in monozygotic twins. Proceedings of the National Academy of Science of the United States of America , 117 (35) pp. 21546-21556. 10.1073/pnas.2003339117. Green open access

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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.

Type: Article
Title: Immune signatures of prodromal multiple sclerosis in monozygotic twins
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1073/pnas.2003339117
Publisher version: https://doi.org/10.1073/pnas.2003339117
Language: English
Additional information: © 2020 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/).
Keywords: autoimmunity, biomarker, immune phenotyping, monozygotic twins, multiple sclerosis
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Brain Repair and Rehabilitation
URI: https://discovery.ucl.ac.uk/id/eprint/10109503
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