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Besides the initial interest in the contribution of sex\u2010steroid hormone signaling, the role of genetic factors linked to the X chromosome has recently received much attention. In humans and mice, the number of X chromosomes, rather than sex\u2010steroid hormones, is associated with a higher risk to develop autoimmunity, particularly rheumatic diseases, such as SLE, Sj\u00f6gren's syndrome, or systemic sclerosis. In this review, we will summarize the recent advances in the various mechanisms and pathways involving the X chromosome in female sex\u2010biased autoimmune diseases. We will particularly focus on the experimental evidence suggesting that expression of X\u2010linked genes due to dysregulation in X chromosome inactivation maintenance could contribute to the female predisposition for autoautoimmunity.<\/jats:p>","DOI":"10.1002\/eji.202451331","type":"journal-article","created":{"date-parts":[[2025,5,26]],"date-time":"2025-05-26T07:35:14Z","timestamp":1748244914000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["The Inactive X Chromosome: A Genetic Driver of Female\u2010Biased Rheumatic Autoimmune Disorders?"],"prefix":"10.1002","volume":"55","author":[{"given":"L\u00e9a","family":"Ferray\u00e9","sequence":"first","affiliation":[{"name":"Toulouse Institute for Infectious and Inflammatory Diseases (INFINITY) Universit\u00e9 de Toulouse, INSERM, CNRS  Toulouse 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