Women are 4-times more likely to have autoimmune diseases than men. Why is this? From Dou et al. in Cell, today In females, the second X chromosome is silenced by a long non-coding RNA, called Xist (pronounced 'exist') - males don't express Xist Xist, together with almost 100 unique proteins, wraps itself around the second X chromosome, silencing it. It's thought that Xist-protein complexes are highly immunogenic, and may represent targets for autoantibodies Dou et al. devised a system to induce expression of Xist in male mice. They found that Xist expression led to the production of autoantibodies, similar to levels found in female mice (RIBO P0/P2 are lupus autoantibodies, CENPA/B are scleroderma autoantibodies): In a mouse model, these autoantibodies in Xist-expressing males were sufficient to cause significant lupus pathology (including in the kidney and the lung): In humans, autoantibodies against the Xist ribonucleoprotein complex were enriched in female patients with lupus, scleroderma, and dermatomyositis Therefore, Xist may solve the puzzle of female-biased autoimmunity cell.com/action/showPdf?pii=…