Immune signatures of prodromal multiple sclerosis in monozygotic twins
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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; Kümpfel, Tania; Wiendl, Heinz; Hohlfeld, Reinhard; Klotz, Luisa.
In: P NATL ACAD SCI USA, Vol. 117, No. 35, 01.09.2020, p. 21546-21556.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Immune signatures of prodromal multiple sclerosis in monozygotic twins
AU - Gerdes, Lisa Ann
AU - Janoschka, Claudia
AU - Eveslage, Maria
AU - Mannig, Bianca
AU - Wirth, Timo
AU - Schulte-Mecklenbeck, Andreas
AU - Lauks, Sarah
AU - Glau, Laura
AU - Gross, Catharina C
AU - Tolosa, Eva
AU - Flierl-Hecht, Andrea
AU - Ertl-Wagner, Birgit
AU - Barkhof, Frederik
AU - Meuth, Sven G
AU - Kümpfel, Tania
AU - Wiendl, Heinz
AU - Hohlfeld, Reinhard
AU - Klotz, Luisa
N1 - Copyright © 2020 the Author(s). Published by PNAS.
PY - 2020/9/1
Y1 - 2020/9/1
N2 - 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.
AB - 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.
U2 - 10.1073/pnas.2003339117
DO - 10.1073/pnas.2003339117
M3 - SCORING: Journal article
C2 - 32817525
VL - 117
SP - 21546
EP - 21556
JO - P NATL ACAD SCI USA
JF - P NATL ACAD SCI USA
SN - 0027-8424
IS - 35
ER -
