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Ostkamp, Patrick; Salmen, Anke; Pignolet, Beatrice; Görlich, Dennis; Andlauer, Till F. M.; Schulte-Mecklenbeck, Andreas; Gonzalez-Escamilla, Gabriel; Bucciarelli, Florence; Gennero, Isabelle; Breuer, Johanna; Antony, Gisela; Schneider-Hohendorf, Tilman; Mykicki, Nadine; Bayas, Antonios; Bergh, Florian Then; Bittner, Stefan; Hartung, Hans-Peter; Friese, Manuel A.; Linker, Ralf A.; Luessi, Felix; Lehmann-Horn, Klaus; Mühlau, Mark; Paul, Friedemann; Stangel, Martin; Tackenberg, Björn; Tumani, Hayrettin; Warnke, Clemens; Weber, Frank; Wildemann, Brigitte; Zettl, Uwe K.; Ziemann, Ulf; Müller-Myhsok, Bertram; Kümpfel, Tania; Klotz, Luisa; Meuth, Sven G.; Zipp, Frauke; Hemmer, Bernhard; Hohlfeld, Reinhard; Brassat, David; Gold, Ralf; Gross, Catharina C.; Lukas, Carsten; Groppa, Sergiu; Loser, Karin; Wiendl, Heinz und Schwab, Nicholas (2021): Sunlight exposure exerts immunomodulatory effects to reduce multiple sclerosis severity. In: Proceedings of the National Academy of Sciences of the United States of America, Bd. 118, Nr. 1, e2018457118

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Abstract

Multiple sclerosis (MS) disease risk is associated with reduced sunexposure. 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 (n(NationMS) = 946, n(BIONAT) = 990). Additionally, effect-modification by medication and photosensitivity-associated MC1R 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-beta-treated patients. In carriers of MC1R: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 benefidal 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.

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