First characterization of the transcriptome of lung fibroblasts of SSc patients and healthy donors of African ancestry.. First characterization of the transcriptome of lung fibroblasts of SSc patients and healthy donors of African ancestry.

Systemic sclerosis (SSc) is a rare and devastating connective tissue disorder that results in fibrosis and vascular abnormalities that affect the skin and visceral organs, and SSc-associated pulmonary fibrosis (SSc-PF) is the leading cause of death amongst SSc patients. Racial disparity is noticeable in SSc as African Americans (AA) have a higher frequency and severity of diseases than European Americans (EA). Using RNAseq, we determined differentially expressed genes (DEGs) in primary pulmonary fibroblasts (pFBs) outgrown from SSc-PF lungs (SScL) and normal lungs (NL) of AA and EA patients to characterize the unique transcriptomic signatures of AA-NL and AA-SScL pFBs by performing a systems level analysis. We identified 69 DEGs in “AA-NL vs. EA-NL” and 384 DEGs in “AA-SScL vs. EA-SScL” comparisons, and only 7.5% DEGs were commonly deregulated in the “SScL vs. NL in AA and EA” disease mechanisms comparison. Surprisingly, we also identified a disease-like signature in AA-NL pFBs. Our data highlight that the transcriptome of AA pFBs is unique and may hold the key to understanding racial disparity in SSc-PF, the first step in developing efficacious therapeutic strategies. Overall design: differential expression analysis between (1) normal lung (NL) pulmonary fibroblasts (pFBs) of African American (AA) and European Americans (EA) donors "AA-NL vs. EA-NL"; (2) SSc-PF pFBs (SScL) and NL pFBs in AA and EA: "AA-SScL vs. AA-NL" and "EA-SScL vs. EA-NL" followed by venn comparison; (3) "AA-SScL vs. EA-SScL"