Objective. T cells treated with DNA methylation inhibitors overexpress lymphocyte function‐associated antigen 1 (LFA‐1), which results in autoreactivity, and the autoreactive cells cause a lupus‐like disease in vivo, suggesting a mechanism by which some agents may cause drug‐induced lupus. This study compared the effects of procainamide (Pca) and hydralazine (Hyd) with those of structural analogs, to determine if the degree of LFA‐1 overexpression and T cell autoreactivity correlated with the ability of the agents to induce autoimmunity.

Methods. Cloned murine T helper 2 cells were treated with Pca, N‐acetylprocainamide, Hyd, Phthalazine, or hydroxyurea (HU). The treated cells were then compared for LFA‐1 overexpression, autoreactivity, and the ability to induce autoimmunity in vivo.

Results. Pca and Hyd were more potent than their analogs or HU in all 3 assays.

Conclusion. The results support a relationship between LFA‐1 overexpression, T cell autoreactivity, and autoimmunity, and suggest a mechanism by which Pca and Hyd, but not the analogs, may cause drug‐induced lupus.