Clinical Significance of Autoantibodies to P53 Protein in Patients with Autoimmune Liver Diseases

Abstract

Autoantibodies to p53 (anti-p53) are rarely present in the sera of patients with autoimmune diseases or the sera of patients with malignancies. To examine the prevalence of anti-p53 in patients with autoimmune liver disease including autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), AIH⁄PBC overlap syndrome (AIH⁄PBC OS) and primary sclerosing cholangitis (PSC), and to determine the clinical significance of anti-p53 in autoimmune liver diseases. Forty patients with AIH, 41 patients with PBC, eight patients with AIH⁄PBC OS and five patients with PSC were enrolled. Anti-p53 and antibodies to double-stranded DNA (anti-ds-DNA) were analyzed using commercially available ELISA kits. Demographic, laboratory and histological data were compared between the AIH groups seropositive and seronegative for anti-p53. Six of 40 (15.0%) patients with AIH and four of eight (50.0%) patients with AIH⁄PBC OS were positive for anti-p53. One of 41 (2.4%) patients with PBC was also positive for anti-p53, but all five patients with PSC were negative, indicating a significantly higher prevalence of anti-p53 in patients with AIH or AIH⁄PBC OS compared with patients with PBC. None of the AIH patients positive for anti-p53 progressed to hepatic failure or relapsed after immunosuppressive treatment. Titres of anti-ds-DNA in patients with AIH and AIH⁄PBC OS significantly correlated with titres of anti-p53 (r=0.511; P=0.0213). The emergence of anti-p53 is likely to be useful for discriminating AIH or AIH⁄PBC OS from PBC and helpful for predicting favourable prognoses in patients with AIH. DNA damage may trigger the production of anti-p53 in patients with AIH or AIH⁄PBC OS.