Ostkamp, PatrickPatrickOstkampSalmen, AnkeAnkeSalmenPignolet, BéatriceBéatricePignoletGörlich, DennisDennisGörlichAndlauer, Till F MTill F MAndlauerSchulte-Mecklenbeck, AndreasAndreasSchulte-MecklenbeckGonzalez-Escamilla, GabrielGabrielGonzalez-EscamillaBucciarelli, FlorenceFlorenceBucciarelliGennero, IsabelleIsabelleGenneroBreuer, JohannaJohannaBreuerAntony, GiselaGiselaAntonySchneider-Hohendorf, TilmanTilmanSchneider-HohendorfMykicki, NadineNadineMykickiBayas, AntoniosAntoniosBayasThen Bergh, FlorianFlorianThen BerghBittner, StefanStefanBittnerHartung, Hans-PeterHans-PeterHartungFriese, Manuel AManuel AFrieseLinker, Ralf ARalf ALinkerLuessi, FelixFelixLuessiLehmann-Horn, KlausKlausLehmann-HornMühlau, MarkMarkMühlauPaul, FriedemannFriedemannPaulStangel, MartinMartinStangelTackenberg, BjörnBjörnTackenbergTumani, HayrettinHayrettinTumaniWarnke, ClemensClemensWarnkeWeber, FrankFrankWeberWildemann, BrigitteBrigitteWildemannZettl, Uwe KUwe KZettlZiemann, UlfUlfZiemannMüller-Myhsok, BertramBertramMüller-MyhsokKümpfel, TaniaTaniaKümpfelKlotz, LuisaLuisaKlotzMeuth, Sven GSven GMeuthZipp, FraukeFraukeZippHemmer, BernhardBernhardHemmerHohlfeld, ReinhardReinhardHohlfeldBrassat, DavidDavidBrassatGold, RalfRalfGoldGross, Catharina CCatharina CGrossLukas, CarstenCarstenLukasGroppa, SergiuSergiuGroppaLoser, KarinKarinLoserWiendl, HeinzHeinzWiendlSchwab, NicholasNicholasSchwab2024-09-022024-09-022021-01-05https://boris-portal.unibe.ch/handle/20.500.12422/39368Multiple 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 (nNationMS = 946, nBIONAT = 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.enlatitude melanocortin 1 receptor multiple sclerosis sunlight vitamin D600 - Technology::610 - Medicine & healtharticle10.48350/1507523337620210.1073/pnas.2018457118