IntroductionSystemic Lupus Erythematosus (SLE) exhibits a pronounced sex bias, affecting females approximately nine times more frequently than males; however, males tend to experience a more severe clinical course yet the molecular basis for these differences remains unclear. MethodsLeveraging epigenomic, transcriptomic, and proteomic data from the whole blood of 720 SLE patients (679 females, 41males) and 84 healthy controls (77 females, 7 males), we conducted comprehensive multi-omic analyses to identify sex-specific molecular features of this disease.
Specifically, differential expression analysis for each modality was conducted using a factorial design to identify differences between disease and healthy controls (SLE–HC) for each sex, as well as the interaction effects between send and disease ([Male SLE – Male HC] – [Female SLE – Female HC]). Benjamini & Hochberg false discovery rate (FDR) was used for multiple test correction.ResultsThe strongest signal differentiating males and females with SLE was the aberrant expression of the long non-coding RNA, XIST, in males.
This XIST expression in males with SLE was bimodal, with 54% of males having elevated XIST expression, and correlated with disease severity.
Frontiers in Immunology published a clinical update in Infectious Disease on 06 Apr 2026.
The item focuses on XIST expression and hypermethylation of the X chromosome in males with systemic lupus erythematosus.
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