Sunlight exposure exerts immunomodulatory effects to reduce multiple sclerosis severity.

Frauke Zipp, Björn Tackenberg, Hayrettin Tumani, Clemens Warnke, Frank Weber, Brigitte Wildemann, Uwe K Zettl, Ulf Ziemann, Bertram Müller-Myhsok, Tania Kümpfel, Luisa Klotz, Sven G Meuth, Martin Stangel, Bernhard Hemmer, Reinhard Hohlfeld, David Brassat, Ralf Gold, Catharina C Gross, Carsten Lukas, Sergiu Groppa, Karin Loser, Heinz Wiendl, Nicholas Schwab, Nadine Mykicki, Anke Salmen, Béatrice Pignolet, Dennis Görlich, Till F M Andlauer, Andreas Schulte-Mecklenbeck, Gabriel Gonzalez-Escamilla, Florence Bucciarelli, Isabelle Gennero, Johanna Breuer, Gisela Antony, Tilman Schneider-Hohendorf, Patrick Ostkamp, Antonios Bayas, Florian Then Bergh, Stefan Bittner, Hans-Peter Hartung, Manuel A Friese, Ralf A Linker, Felix Luessi, Klaus Lehmann-Horn, Mark Mühlau, Friedemann Paul

Journal: Proceedings of the National Academy of Sciences of the United States of America 2021;118(1):e2018457118

PMID: 33376202

Abstract

Multiple sclerosis (MS) disease risk is associated with reduced sun-exposure. This study assessed the relationship between measures of sun exposure (vitamin D [vitD], latitude) and MS severity in the setting of two multicenter cohort studies ( = 946, = 990). Additionally, effect-modification by medication and photosensitivity-associated variants was assessed. High serum vitD was associated with a reduced MS severity score (MSSS), reduced risk for relapses, and lower disability accumulation over time. Low latitude was associated with higher vitD, lower MSSS, fewer gadolinium-enhancing lesions, and lower disability accumulation. The association of latitude with disability was lacking in IFN-β-treated patients. In carriers of :rs1805008(T), who reported increased sensitivity toward sunlight, lower latitude was associated with higher MRI activity, whereas for noncarriers there was less MRI activity at lower latitudes. In a further exploratory approach, the effect of ultraviolet (UV)-phototherapy on the transcriptome of immune cells of MS patients was assessed using samples from an earlier study. Phototherapy induced a vitD and type I IFN signature that was most apparent in monocytes but that could also be detected in B and T cells. In summary, our study suggests beneficial effects of sun exposure on established MS, as demonstrated by a correlative network between the three factors: Latitude, vitD, and disease severity. However, sun exposure might be detrimental for photosensitive patients. Furthermore, a direct induction of type I IFNs through sun exposure could be another mechanism of UV-mediated immune-modulation in MS.

Copyright © 2021 the Author(s). Published by PNAS.

Address: Department of Neurology with Institute of Translational Neurology, University of Muenster, 48149 Muenster, Germany.; Neurology, St. Josef-Hospital, Ruhr-University Bochum, 44801 Bochum, Germany.; Neurology, Inselspital, Bern University Hospital, University of Bern, 3012 Bern, Switzerland.; Neurosciences Department, Centres de Ressources et de Compétences-Sclérose en Plaques, Centre Hospitalier Univeresitaire Toulouse, 31300 Toulouse, France.; Center for Physiopathology of Toulouse Purpan, INSERM U1043-CNRS U5282, Université Toulouse III, 31330 Toulouse, France.; Institute of Biostatistics and Clinical Research, University of Muenster, 48149 Muenster, Germany.; Max Planck Institute of Psychiatry, 80804 Munich, Germany.; Department of Neurology, School of Medicine, Technical University of Munich, 80333 Munich, Germany.; Department of Neurology, Focus Program Translational Neuroscience, Rhine Main Neuroscience Network, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany.; Institut Federatif de Biologie, Centre Hospitalier Univeresitaire Toulouse, Purpan University Hospital, 31300 Toulouse, France.; Central Information Office German Competence Network of Multiple Sclerosis, Philipps-University Marburg, 35037 Marburg, Germany.; Department of Dermatology, University of Muenster, 48149 Muenster, Germany.; Department of Neurology, University Hospital Augsburg, 86156 Augsburg, Germany.; Department of Neurology, University of Leipzig, 04109 Leipzig, Germany.; Department of Neurology, Medical Faculty, Heinrich Heine University, 40225 Düsseldorf, Germany.; Institute of Neuroimmunology and Multiple Sclerosis, Center for Molecular Neurobiology Hamburg, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany.; Department of Neurology, University of Regensburg, 93053 Regensburg, Germany.; Munich Cluster for Systems Neurology, 81377 Munich, Germany.; Technische Universität München-Neuroimaging Center, Klinikum Rechts der Isar, Technische Universität München, 80333 Munich, Germany.; NeuroCure Clinical Research Center, Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany.; Experimental and Clinical Research Center, Max Delbrück Center for Molecular Medicine and Charité-Universitätsmedizin Berlin, 13125 Berlin, Germany.; Department of Neurology, Charité-Universitätsmedizin Berlin, 13125 Berlin, Germany.; Berlin Institute of Health, 10178 Berlin, Germany.; Clinical Neuroimmunology and Neurochemistry, Department of Neurology, Hannover Medical School, 30625 Hannover, Germany.; Clinical Neuroimmunology Group, Department of Neurology, Philipps-University of Marburg, 35037 Marburg, Germany.; Department of Neurology, University of Ulm, 89081 Ulm, Germany.; Clinic of Neurology Dietenbronn, 88477 Schwendi, Germany.; Department of Neurology, University Hospital Cologne, 50924 Cologne, Germany.; Neurological Clinic Cham, Sana Kliniken des Landkreises Cham GmbH, 93413 Cham, Germany.; Department of Neurology, University Hospital Heidelberg, 69120 Heidelberg, Germany.; Department of Neurology, Neuroimmunological Section, University of Rostock, 18051 Rostock, Germany.; Department of Neurology & Stroke, Eberhard-Karls-Universität Tübingen, 72074 Tübingen, Germany.; Institute of Translational Medicine, University of Liverpool, Liverpool L69 3BX, United Kingdom.; Institute of Clinical Neuroimmunology, Biomedical Center and University Hospital, Ludwig-Maximilians-University of Munich, 80539 Munich, Germany.; Focus Program Translational Neurosciences, Johannes Gutenberg University Mainz, 55122 Mainz, Germany.; Research Center for Immunotherapy, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany.; Rhine-Main Neuroscience Network, University Medical Center of the Johannes Gutenberg University Mainz, 55131 Mainz, Germany.; Institute of Neuroradiology Ruhr, University Bochum and St. Josef-Hospital, 44791 Bochum, Germany.; Department of Neurology with Institute of Translational Neurology, University of Muenster, 48149 Muenster, Germany; [email protected] [email protected].
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