Manganese superoxide dismutase-inhibiting autoantibodies in cholestatic Epstein-Barr viral hepatitis

HISTORY AND CLINICAL FINDINGS: A 21-year-old woman reported no serious previous illness. For 3 days before admission she had a fever, headache and joint pains. She had become progressively more jaundiced. Physical examination was normal except for enlarged liver and spleen, swollen lymph nodes and facial oedema. INVESTIGATIONS: GOT (30 U/l), GPT (33 U/l) and alkaline phosphatase (172 U/l) were slightly elevated. Serum bilirubin was raised to 12.4 mg/dl. The total white blood cell count was normal, but there were 45% atypical lymphocytes (activated T lymphocytes). Abdominal sonography and endoscopic retrograde cholangiopancreatography were unremarkable. Serology for hepatitis A, B and C as well as for antimitochondrial antibodies was negative, but there were specific IgM (1:640) and IgG antibodies (1:80) against Epstein-Barr virus (EBV) capsid antigen in the immunofluorescence test. DIAGNOSIS, TREATMENT AND COURSE: The EBV infection (infectious mononucleosis) was complicated by cholestatic hepatitis. High concentrations (1832 G?ttingen units/ml) of enzyme-inhibiting autoantibodies against the antioxidative enzyme manganese-superoxide dismutase (MSD) were demonstrated. The autoantibodies reduced the antioxidative action of the enzyme by more than 70% and favoured the oxidative cell damage in vitro. After bed-rest for one week without further treatment the symptoms improved and the abnormal laboratory values, including the autoantibodies against MSD, regressed. CONCLUSION: Autoantibodies against MSD are formed during an acute infection with EBV. Their enzyme-inhibiting action promotes abnormalities of oxidative cell function and may thus be the cause of cholestatic hepatitis in this infection.