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• W3045394911 abstract "Abstract Background 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 disease severity, the mechanisms of action, and effect-modification by medication and sun-sensitivity associated MC1R variants. Methods Two multi-center cohort studies (n NationMS =946, n BIONAT =991). Outcomes were the multiple sclerosis severity score (MSSS) and the number of Gd-enhancing lesion (GELs). RNAseq of four immune cell populations before and after UV-phototherapy of five MS patients. Results High serum vitD was associated with reduced MSSS ( P NationMS =0.021; P BIONAT =0.007) and reduced risk for disease aggravation ( P NationMS =0.032). Low latitude was associated with higher vitD, lower MSSS ( P NationMS =0.018), fewer GELs ( P NationMS =0.030) and reduced risk for aggravation ( P NationMS =0.044). The influence of latitude on disability seemed to be lacking in the subgroup of interferon-β treated patients (interaction- P BIONAT =0.042, interaction- P NationMS =0.053). In genetic analyses, for carriers of MC1R :rs1805008(T), who reported increased sensitivity towards sunlight ( P NationMS =0.038), the relationship between latitude und the number of GELs was inversed ( P NationMS =0.001). Phototherapy induced a vitD and type I interferon signature that was most apparent in the transcriptome of monocytes ( P =1×10 −6 ). Conclusion VitD is associated with reduced MS severity and disease aggravation. This is likely driven by sun-exposure, as latitude also correlated with disability and serum vitD. However, sun-exposure might be detrimental for sun-sensitive patients. A direct induction of type I interferons through sun-exposure could explain a reduced effect of latitude in interferon-β treated patients. This could also explain opposite effects of sun-exposure in MS and the type I interferon and sun-sensitivity-associated disease Lupus." @default.
• W3045394911 created "2020-07-29" @default.
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• W3045394911 date "2020-07-26" @default.
• W3045394911 modified "2023-10-11" @default.
• W3045394911 title "Sunlight exposure exerts immunomodulatory effects to reduce multiple sclerosis severity" @default.
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