Hydralazine and procainamide inhibit T cell DNA methylation and induce autoreactivity.

TLDR

Inhibitors of DNA methylation, such as 5‑azacytidine, induce gene expression and can cause T cells to become auto‑reactive, a phenomenon that may mediate autoimmune disease in vivo. We asked whether drugs known to cause autoimmune disease, specifically hydralazine and procainamide, exert the same effects on T cells as 5‑azacytidine. Hydralazine and procainamide inhibit DNA methylation and induce self‑reactivity in cloned T cell lines, suggesting that drug‑induced autoimmune disease may arise from activation of unidentified genes via DNA methylation mechanisms.

Abstract

Inhibitors of DNA methylation, such as 5-azacytidine, induce gene expression. We have previously reported that cloned T cells treated with 5-azacytidine lose the requirement for Ag and can be activated by autologous HLA-D molecules alone, thus becoming auto-reactive. This phenomenon could potentially mediate an autoimmune disease in vivo. Inasmuch as several drugs are known to cause autoimmune disease, we asked whether they exert the same effects on T cells as 5-azacytidine. We report that hydralazine and procainamide, two drugs associated with a lupus-like autoimmune disease, also inhibit DNA methylation and induce self-reactivity in cloned T cell lines. These results suggest that drug-induced autoimmune disease may be due to activation of as yet unidentified genes through mechanisms involving DNA methylation.