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.
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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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