N-acetylprocainamide is a less potent inducer of t cell autoreactivity than procainamide

✍ Scribed by Bruce Richardson; Elizabeth Cornacchia; Joseph Golbus; Jonathan Maybaum; John Strahler; Samir Hanash

• Publisher: John Wiley and Sons
• Year: 1988
• Tongue: English
• Weight: 494 KB
• Volume: 31
• Category: Article
• ISSN: 0004-3591
• DOI: 10.1002/art.1780310809

✦ Synopsis

We have reported that an inhibitor of DNA methylation, 5-azacytidine, makes cloned, antigenspecific CD4+ T cells autoreactive, and that procainamide and hydralazine mimic this effect. Those results suggested that procainamide and hydralazine may induce autoimmunity by inhibiting DNA methylation and causing T cell autoreactivity. We report now that Nacetylprocainamide, a procainamide derivative that does not induce lupus, is also a DNA methylation inhibitor, but it is 100 times less potent than procainamide in inducing T cell autoreactivity.

DNA methylation inhibitors induce expression of genes normally suppressed by mechanisms associated with cytosine methylation (1) and, in certain systems, can change cellular phenotype and alter differentiation (2,3). We have previously reported that 5-azacytidine (5-azaC), a DNA methylation inhibitor, made 4 cloned antigen-reactive T cells respond to autologous class I1 major histocompatibility complex (MHC) determinants without specific antigen, presumably by inducing expression of suppressed genes (4). This response was termed autoreactivity.

In those studies, we demonstrated that the 5- From the