Patrick Ostkamp, 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, Nadine Mykicki, 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, Martin Stangel, 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, Frauke Zipp, Bernhard Hemmer, Reinhard Hohlfeld, David Brassat, Ralf Gold, Catharina C Gross , Carsten Lukas , Sergiu Groppa , Karin Loser , Heinz Wiendl , Nicholas Schwab , German Competence Network Multiple Sclerosis (KKNMS) and the BIONAT Network

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 (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-β-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 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.

Proc Natl Acad Sci USA 2021 Jan 5;118(1):e2018457118

Link to Pubmed