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. 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"