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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.
Afiliación
  • Gerdes LA; Institute of Clinical Neuroimmunology, University Hospital and Biomedical Center, Ludwig-Maximilians Universität München, 81377 Munich, Germany.
  • Janoschka C; Department of Neurology with Institute of Translational Neurology, University Hospital Münster, Albert-Schweitzer Campus 1, 48149 Münster, Germany.
  • Eveslage M; Institute of Biostatistics and Clinical Research, University of Münster, 48149 Münster, Germany.
  • Mannig B; Department of Neurology with Institute of Translational Neurology, University Hospital Münster, Albert-Schweitzer Campus 1, 48149 Münster, Germany.
  • Wirth T; Department of Neurology with Institute of Translational Neurology, University Hospital Münster, Albert-Schweitzer Campus 1, 48149 Münster, Germany.
  • Schulte-Mecklenbeck A; Department of Neurology with Institute of Translational Neurology, University Hospital Münster, Albert-Schweitzer Campus 1, 48149 Münster, Germany.
  • Lauks S; Department of Neurology with Institute of Translational Neurology, University Hospital Münster, Albert-Schweitzer Campus 1, 48149 Münster, Germany.
  • Glau L; Department of Immunology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
  • Gross CC; Department of Neurology with Institute of Translational Neurology, University Hospital Münster, Albert-Schweitzer Campus 1, 48149 Münster, Germany.
  • Tolosa E; Department of Immunology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
  • Flierl-Hecht A; Institute of Clinical Neuroimmunology, University Hospital and Biomedical Center, Ludwig-Maximilians Universität München, 81377 Munich, Germany.
  • Ertl-Wagner B; Department of Radiology, Grosshadern Medical Campus, Ludwig-Maximilians Universität München, 81377 Munich, Germany.
  • Barkhof F; Department of Medical Imaging, Hospital for Sick Children, University of Toronto, Toronto, ON M5G 1X8, Canada.
  • Meuth SG; University College London Institute of Neurology, University College London, WC1E 6BT London, United Kingdom.
  • Kümpfel T; University College London Institute of Healthcare Engineering, University College London, WC1E 6BT London, United Kingdom.
  • Wiendl H; Department of Radiology and Nuclear Medicine, VU University Medical Center, 1105 AZ Amsterdam, The Netherlands.
  • Hohlfeld R; Department of Neurology with Institute of Translational Neurology, University Hospital Münster, Albert-Schweitzer Campus 1, 48149 Münster, Germany.
  • Klotz L; Institute of Clinical Neuroimmunology, University Hospital and Biomedical Center, Ludwig-Maximilians Universität München, 81377 Munich, Germany.
Proc Natl Acad Sci U S A ; 117(35): 21546-21556, 2020 09 01.
Article en En | MEDLINE | ID: mdl-32817525
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Esclerosis Múltiple Tipo de estudio: Etiology_studies / Incidence_studies / Observational_studies / Risk_factors_studies Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Proc Natl Acad Sci U S A Año: 2020 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Esclerosis Múltiple Tipo de estudio: Etiology_studies / Incidence_studies / Observational_studies / Risk_factors_studies Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Proc Natl Acad Sci U S A Año: 2020 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos