Evidence for impaired t cell dna methylation in systemic lupus erythematosus and rheumatoid arthritis

Procainamide and hydralazine inhibit T cell DNA methylation and induce autoreactivity in cloned CD4+ T cells. These drugs also induce an autoimmune syndrome, suggesting a possible relationship between DNA hypomethylation, T cell autoreactivity, and certain autoimmune diseases. To test this relationship, DNA methylation was studied in T cells from patients with rheumatoid arthritis and patients with systemic lupus erythematosus, and was found to be impaired. These results support a relationship between DNA hypomethylation and some forms of autoimmune disease.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/37783/1/1780331109_ftp.pd

Lymphocyte function—associated antigen 1 overexpression and t cell autoreactivity

Objective . To determine if DNA methylation inhibitors make T cells autoreactive by inducing lymphocyte function—associated antigen type 1 (LFA–1) (CD11a/CD18) overexpression. Methods . T cell clones were treated with 3 distinct DNA methylation inhibitors or were stably transfected with a CD18 cDNA in a mammalian expression vector, and the effects on LFA–1 expression and activation requirements were examined. Results . LFA–1 overexpression, caused by DNA methylation inhibitors or by transfection, correlates with the development of autoreactivity. Conclusion . LFA–1 overexpression may contribute to T cell autoreactivity.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/37802/1/1780370915_ftp.pd