A novel IgM class autoantibody to a hepatocyte‐related 190 kDa molecule in patients with type 1 autoimmune hepatitis

• Published in: Hepatology (Baltimore, Md.) Vol. 40; no. 3; pp. 687 - 692
• Main Authors: Yamauchi, Katsumi, Yamaguchi, Naoko, Furukawa, Takaji, Takatsu, Kazuko, Nakanishi, Toshimi, Sasaki, Mina, Isono, Etsuko, Tokushige, Katsutoshi, Komatsu, Tatsuji, Shiratori, Keiko
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.09.2004; Wiley
• Subjects: Antibodies, Monoclonal - immunology; Autoantibodies - blood; Autoantibodies - physiology; Biological and medical sciences; Cell Line; Complement System Proteins - immunology; Cytotoxicity, Immunologic; Gastroenterology. Liver. Pancreas. Abdomen; Hepatitis, Autoimmune - etiology; Hepatitis, Autoimmune - immunology; Hepatocytes - immunology; Human viral diseases; Humans; Immunoglobulin M - blood; Immunohistochemistry; Infectious diseases; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Medical sciences; Molecular Weight; Other diseases. Semiology; Viral diseases; Viral diseases of the digestive system; Viral hepatitis; Autoimmunity; Hepatic disease; Autoimmune disease; Epstein Barr virus; Monoclonal antibody; IgM; Hepatitis; Tissue; Mononuclear cell; Hepatocyte; Immunoblotting assay; Serum; Clone; Gammaherpesvirinae; Human; Immunoglobulins; Digestive system; Herpesviridae; Autoantibody; Infection; Virus; Blood cell; Cell line; Viral disease; Digestive diseases
• ISSN: 0270-9139; 1527-3350
• DOI: 10.1002/hep.20377

It has been reported that autoantibodies to hepatocytes are frequently found in patients with autoimmune hepatitis (AIH). To elucidate the nature of these hepatocyte‐specific autoantibodies, we attempted to generate a hepatocyte‐specific monoclonal antibody (MoAb) from Epstein‐Barr virus‐transformed peripheral blood mononuclear cells obtained from a patient with AIH. We established a single clone, 2E3, that continued to produce an immunoglobulin M (IgM) antibody (λ‐type). This MoAb had the following properties: it reacted mainly with hepatocyte‐derived cell lines, rather than with other cell lines, and it reacted with liver tissue but not with other tissues. By immunoblot analysis, we found that this MoAb recognized a 190 kDa molecule on hepatocytes. The MoAb was able to kill hepatocyte‐derived cell lines in the presence of fresh human serum. This cytotoxic effect was completely abrogated by heat inactivation of human serum prior to its addition to cell lines. In addition, an IgM autoantibody that recognized a 190 kDa molecule was also found in patients with AIH but not in those with chronic hepatitis C; its titer correlated significantly with serum alanine aminotransferase (ALT) levels in patients with AIH. In conclusion, we generated a human MoAb that recognizes a 190 kDa molecule on hepatocytes. Because of its ability to mediate complement‐dependent cytotoxicity and the presence of similar IgM autoantibody in patients with AIH, we hypothesize this autoantibody may play a role in the immunopathogenesis of AIH. (HEPATOLOGY 2004;40:687–692.)