Autoantibody against activating transcription factor-2 in patients with systemic sclerosis

Objective: To determine the prevalence and clinical correlation of autoantibody to activating transcription factor (ATF)-2, a transcription factor of ATF/CREB family, in patients with systemic sclerosis (SSc). Methods: Anti-ATF-2 Ab was examined by ELISA and immunoblotting using human recombinant ATF-2. ATF-2 activity to bind target DNA was evaluated by ELISA using a plate coated with oligonucleotide containing the consensus binding site for ATF-2. Results: IgG anti-ATF-2 Ab levels in SSc patients (n=69) were significantly higher than those in normal controls (n=26). SSc patients positive for IgG anti-ATF-2 Ab had significantly longer disease duration, more frequent presence of decreased %VC and %DLco, and elevated levels of serum IgG, serum IgA, and erythrocyte sedimentation rates than those negative. More-over, IgG anti-ATF-2 Ab levels correlated inversely with %VC or %DLco. The presence of anti-ATF-2 Ab in SSc patients was confirmed by immunoblotting analysis. IgG isolated from serum samples of SSc patients positive for IgG anti-ATF-2 Ab by ELISA slightly but significantly inhibited ATF-2 activity compared with normal controls. Conclusions: These results suggest that anti-ATF-2 Ab is a new autoantibody in SSc and that it serves as a novel serological marker for inflammation and lung involvement in SSc.