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 (nNationMS=946, nBIONAT=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 (PNationMS=0.021; PBIONAT=0.007) and reduced risk for disease aggravation (PNationMS=0.032). Low latitude was associated with higher vitD, lower MSSS (PNationMS=0.018), fewer GELs (PNationMS=0.030) and reduced risk for aggravation (PNationMS=0.044). The influence of latitude on disability seemed to be lacking in the subgroup of interferon-β treated patients (interaction-PBIONAT=0.042, interaction-PNationMS=0.053). In genetic analyses, carriers of MC1R:rs1805008(T), who reported increased sensitivity towards sunlight (PNationMS=0.038), the relationship between latitude und the number of GELs was inversed (PNationMS=0.001). Phototherapy induced a vitD and type I interferon signature that was most apparent in the transcriptome of monocytes (P=1x10-6). 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.

中文翻译：

---

日光照射具有免疫调节作用，可减轻多发性硬化症的严重程度

背景：多发性硬化症（MS）的疾病风险与日晒减少有关。这项研究评估了阳光照射（维生素D（vitD），纬度）与MS疾病严重程度，作用机理以及药物和阳光敏感性相关MC1R变异对效果的影响之间的关系。方法：两项多中心队列研究（nNationMS = 946，nBIONAT = 991）。结果是多发性硬化症严重程度评分（MSSS）和Gd增强病变的数量（GEL）。五名MS患者在接受紫外线光疗之前和之后的四个免疫细胞群的RNAseq。结果：高血清vitD与降低MSSS（PNationMS = 0.021； PBIONAT = 0.007）和降低疾病加重风险（PNationMS = 0.032）相关。低纬度与较高的vitD，较低的MSSS（PNationMS = 0.018）和较少的GEL（PNationMS = 0）相关。030）和降低的加重风险（PNationMS = 0.044）。在干扰素-β治疗的患者亚组中似乎缺乏纬度对残疾的影响（interaction-PBIONAT = 0.042，interaction-PNationMS = 0.053）。在遗传分析中，MC1R：rs1805008（T）的携带者报告了对日光的敏感性增加（PNationMS = 0.038），纬度与GEL数量之间的关系相反（PNationMS = 0.001）。光疗诱导了vitD和I型干扰素签名，这在单核细胞的转录组中最为明显（P = 1x10-6）。结论：VitD与降低的MS严重程度和疾病加重有关。这可能是由于阳光暴晒，因为纬度也与残疾和血清vitD相关。但是，日晒对阳光敏感的患者可能有害。通过日晒直接诱导I型干扰素可以解释干扰素-β治疗的患者纬度降低的影响。这也可以解释暴露在MS中的相反作用以及I型干扰素和与太阳敏感性相关的疾病狼疮。