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Immune Signatures of Prodromal Multiple Sclerosis in Monozygotic Twins

30 Pages Posted: 5 Sep 2019 Sneak Peek Status: Review Complete

See all articles by Lisa Ann Gerdes

Lisa Ann Gerdes

Ludwig Maximilian University of Munich (LMU)

Claudia Janoschka

University Hospital Münster - Clinic of Neurology with Institute of Translational Neurology

Maria Eveslage

University of Muenster

Bianca Mannig

University Hospital Münster - Clinic of Neurology with Institute of Translational Neurology

Timo Wirth

University Hospital Münster - Clinic of Neurology with Institute of Translational Neurology

Andreas Schulte-Mecklenbeck

University Hospital Münster - Clinic of Neurology with Institute of Translational Neurology

Sarah Lauks

University Hospital Münster - Clinic of Neurology with Institute of Translational Neurology

Laura Glau

University Medical Center Hamburg-Eppendorf

Catharina C. Groß

University Hospital Münster - Clinic of Neurology with Institute of Translational Neurology

Eva Tolosa

University Medical Center Hamburg-Eppendorf

Andrea Flierl-Hecht

Ludwig Maximilian University of Munich (LMU)

Birgit Ertl-Wagner

Ludwig Maximilian University of Munich (LMU)

Frederik Barkhof

VU University Amsterdam - Amsterdam Neuroscience; University College London - Institute of Neurology; University College London

Sven G. Meuth

University Hospital Münster - Clinic of Neurology with Institute of Translational Neurology

Tania Kümpfel

Ludwig Maximilian University of Munich (LMU)

Heinz Wiendl

German Competence Network Multiple Sclerosis (KKNMS); University Hospital Münster - Clinic of Neurology with Institute of Translational Neurology

Reinhard Hohlfeld

Ludwig Maximilian University of Munich (LMU)

Luisa Klotz

University Hospital Münster - Clinic of Neurology with Institute of Translational Neurology

More...

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 investigated a unique cohort of monozygotic twin pairs who were clinically discordant for MS. Notably, a subgroup of the clinically healthy twins exhibited signs of subclinical, prodromal MS. Comprehensive immune phenotyping revealed that in the overall cohort, the immune signatures of MS-affected and unaffected co-twins were remarkably similar. Twinship alone contributed 68% of the immune variation, whereas age, sex and MS together only contributed 8%. However, distinct traits in CD4+ and CD8+ effector T cell populations emerged when we focused on the subgroup with prodromal MS. 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 points to a key role of T cells in MS disease initiation.

Keywords: monozygotic twin study, prodromal multiple sclerosis, deep immune phenotyping

Suggested Citation

Gerdes, Lisa Ann and Janoschka, Claudia and Eveslage, Maria and Mannig, Bianca and Wirth, Timo and Schulte-Mecklenbeck, Andreas and Lauks, Sarah and Glau, Laura and Groß, Catharina C. and Tolosa, Eva and Flierl-Hecht, Andrea and Ertl-Wagner, Birgit and Barkhof, Frederik and Meuth, Sven G. and Kümpfel, Tania and Wiendl, Heinz and Hohlfeld, Reinhard and Klotz, Luisa, Immune Signatures of Prodromal Multiple Sclerosis in Monozygotic Twins (September 3, 2019). IMMUNITY-D-19-00879. Available at SSRN: https://ssrn.com/abstract=3447318 or http://dx.doi.org/10.2139/ssrn.3447318
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Lisa Ann Gerdes

Ludwig Maximilian University of Munich (LMU) ( email )

Geschwister-Scholl-Platz 1
Munich, Bavaria 80539
Germany

Claudia Janoschka

University Hospital Münster - Clinic of Neurology with Institute of Translational Neurology ( email )

Germany

Maria Eveslage

University of Muenster ( email )

Schlossplatz 2
Muenster, D-48149
Germany

Bianca Mannig

University Hospital Münster - Clinic of Neurology with Institute of Translational Neurology ( email )

Germany

Timo Wirth

University Hospital Münster - Clinic of Neurology with Institute of Translational Neurology ( email )

Germany

Andreas Schulte-Mecklenbeck

University Hospital Münster - Clinic of Neurology with Institute of Translational Neurology ( email )

Germany

Sarah Lauks

University Hospital Münster - Clinic of Neurology with Institute of Translational Neurology ( email )

Germany

Laura Glau

University Medical Center Hamburg-Eppendorf ( email )

Martinistrasse 52
Hamburg, D - 20246
Germany

Catharina C. Groß

University Hospital Münster - Clinic of Neurology with Institute of Translational Neurology ( email )

Germany

Eva Tolosa

University Medical Center Hamburg-Eppendorf ( email )

Martinistrasse 52
Hamburg, D - 20246
Germany

Andrea Flierl-Hecht

Ludwig Maximilian University of Munich (LMU) ( email )

Geschwister-Scholl-Platz 1
Munich, Bavaria 80539
Germany

Birgit Ertl-Wagner

Ludwig Maximilian University of Munich (LMU) ( email )

Geschwister-Scholl-Platz 1
Munich, Bavaria 80539
Germany

Frederik Barkhof

VU University Amsterdam - Amsterdam Neuroscience

Amsterdam
Netherlands

University College London - Institute of Neurology

Queen Square
London WC1N 3BG
United Kingdom

University College London

Gower Street
London, WC1E 6BT
United Kingdom

Sven G. Meuth

University Hospital Münster - Clinic of Neurology with Institute of Translational Neurology ( email )

Germany

Tania Kümpfel

Ludwig Maximilian University of Munich (LMU)

Geschwister-Scholl-Platz 1
Munich, Bavaria 80539
Germany

Heinz Wiendl

German Competence Network Multiple Sclerosis (KKNMS)

Germany

University Hospital Münster - Clinic of Neurology with Institute of Translational Neurology

Germany

Reinhard Hohlfeld

Ludwig Maximilian University of Munich (LMU) ( email )

Geschwister-Scholl-Platz 1
Munich, Bavaria 80539
Germany

Luisa Klotz (Contact Author)

University Hospital Münster - Clinic of Neurology with Institute of Translational Neurology ( email )

Germany

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