Anti-p53 autoantibody in systemic sclerosis: association with limited cutaneous systemic sclerosis

OBJECTIVE: To determine the prevalence and clinical significance of anti-p53 antibody in patients with systemic sclerosis (SSc). METHODS: Anti-p53 antibody was examined by ELISA and immunoblotting. Findings were correlated with clinical features of disease and other autoantibodies and compared with other connective tissue diseases as well as normal controls. p53 activity to bind target DNA was evaluated by ELISA using a plate coated with oligonucleotide containing the consensus binding site for p53. RESULTS: IgG anti-p53 antibody levels were elevated in patients with SSc compared to patients with systemic lupus erythematosus (n = 20; p < 0.05), dermatomyositis (n = 21; p < 0.005), atopic dermatitis (n = 17; p < 0.0005), or bullous pemphigoid (n = 10; p < 0.0005) and normal controls (n = 21; p < 0.0005). Remarkably, anti-p53 antibody levels were higher in patients with limited cutaneous SSc (lSSc; n = 30) than those found in patients with diffuse cutaneous SSc (dSSc; n = 40; p < 0.05). IgG or IgM anti-p53 antibody levels did not correlate with the presence or levels of other autoantibodies. IgG anti-p53 antibody was associated with longer disease duration (p < 0.05) and decreased percentage vital capacity (p < 0.05), and correlated negatively with modified Rodnan total skin thickness score (r = -0.352, p < 0.01). Immunoblotting analysis confirmed the presence of IgG anti-p53 antibody in selected patients with SSc. IgG isolated from sera of selected patients with SSc that contained IgG anti-p53 antibody inhibited the p53 activity relative to normal controls. CONCLUSION: IgG anti-p53 antibody was detected in lSSc and dSSc, and was more prominent in lSSc, indicating that IgG anti-p53 antibody is a novel autoantibody associated with lSSc, a milder form of SSc.