Sex differences in the molecular basis of multiple sclerosis: meta-analysis of transcriptomic data

Multiple sclerosis (MS), an auto-immune, inflammatory, and degenerative disorder of the central nervous system, affects both males and females; however, females are at an increased risk of developing MS (2-3:1 ratio compared to males). The factors behind these sex differences are not still clear. Therefore, the aim of this work has been to explore the role of sex in MS to identify potential molecular mechanisms underlying sex-based differences. To this end, we performed a systematic review in public databases of transcriptomic studies, in nervous tissue and blood. Next, we performed 3 meta-analyses that allowed us to detect MS alterations in females, in males and between both sexes. As a result of our work, we selected 9 studies (4 of nerve tissue and 5 of blood) containing 474 individuals. Our meta-analyses identified some genes and functions altered on a sex-specific or between-sex basis. Among them, highlight 15 genes that showed a significantly different expression pattern between sexes in some of the tissues analyzed: (KIR2DL3 in blood; ARL17B, CECR7, CEP78, IFFO2, LOC401127, NUDT18, RNF10, SLC17A5, STEMP1, TRAF3IP2-AS1, UBXN2B, ZNF117, ZNF488 in nervous tissue; LOC 102723701 in both tissues). This work evidences the existence of sex differences in MS at the transcriptomic level and, moreover, open the door to future applications leading to more sex-specific treatments.</p