Systemic sclerosis (SSc) is a fibrotic disease with high mortality. SSc-associated pulmonary fibrosis (SSc-PF) is currently the leading cause of death. SSc shows a significant sex disparity, with an average sex ratio of 1:5 men to women, yet SSc-PF is more severe in men. We compared gene expression profiles of SSc-PF lung tissues from male and female donors. Whole lung tissues from healthy donors and SSc-PF patients of both sexes were analyzed by RNA sequencing. Selected genes were validated by quantitative polymerase chain reaction and Western blotting analyses. Our results show that genes related to extracellular matrix production were upregulated in females, while genes that are less explicitly related to fibrosis were upregulated in males. Additionally, recombinant transforming growth factor beta (TGFβ) elicited a different response in female and male normal lung fibroblasts. Further, the transcriptomic signatures in male and female lungs only overlapped by 9.19%, highlighting that SSc-PF progresses using different pathways in individuals of different sex. Furthermore, this sex-specific signature of SSc-PF highlights the importance of precision medicine when considering disease-modulating therapies.
Galimba et al. (Thu,) studied this question.