Transcriptome analysis of ankylosing spondylitis patients before and after TNF-a inhibitor therapy reveals the pathways affected

Tumor necrosis factor - α (TNF - α) inhibitors are highly effective in suppressing inflammation in ankylosing spondylitis (AS) patients, and operate by suppression of TFN-α and downstream immunological pathways. To determine the mechanisms of action of TNF-α inhibitors in AS patients, we used transcriptomic and bioinformatic approaches on peripheral blood mononuclear cells from AS patients pre– and post-treatment. We found 656 differentially expressed genes, including the genome-wide significant AS-associated genes, IL6R, NOTCH1, IL10, CXCR2, and TNFRSF1A. A distinctive gene expression profile was found between male and female patients, mainly due to sex chromosome-linked genes and IL17RC, potentially accounting for the differences in clinical manifestation and treatment response between the genders. In addition to immune and inflammation regulatory pathways, KEGG pathway analyses revealed that infection-associated and metabolism-associated pathways were involved in response to TNF-α inhibitor treatment, providing insight to the mechanism of TNF-α inhibitors