Hepatocytes of double-transgenic mice expressing high levels of hepatitis B virus e antigen and interferon-gamma are not injured by HBeAg specific autoantibodies.
Seroconversion from HBeAg to alphaHBe of persons chronically infected by HBV is usually associated with a transient exacerbation of liver disease and subsequent normalization of liver histology. It is speculated that these clinico-pathological features may be due to the activation of cytodestructive mechanisms by alphaHBe antibodies. The aim of the present study was to investigate the pathogenic potential of alphaHBe antibodies in a transgenic mouse model. Therefore, alphaHBe autoantibodies were elicited in double-transgenic mice expressing high amounts of HBeAg and interferon-gamma in the liver. Interferon-gamma has reviously been shown to play an important role in the development of hepatic necroinflammation associated with hepadnaviral infection, probably via tumor-necrosis-factor-alpha secreted by activated macrophages. We found no evidence that alphaHBe antibodies have the potential to destroy HBeAg-secreting hepatocytes even if the cells were predisposed to injury due to high-level interferon-gamma expression. We conclude that seroconversion from HBeAg to alphaHBe of persons chronically infected with HBV seems to be an immunological epiphenomenon without pathogenic significance.
Merkle
H
H
Department of Internal Medicine I, University of Ulm, Germany.
Nusser
P
P
Knehr
S
S
Löhler
J
J
Barsig
J
J
Yamamura
K I
KI
Reifenberg
K
K
D000818:Animals; D000918:Antibody Specificity; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D002460:Cell Line; D005434:Flow Cytometry; D006509:Hepatitis B / Q000276:immunology* / Q000473:pathology / Q000821:virology; D006510:Hepatitis B Antibodies / Q000097:blood; D006513:Hepatitis B e Antigens / Q000276:immunology* / Q000378:metabolism; D016898:Interferon-alpha / Q000096:biosynthesis / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology*; D008099:Liver / Q000166:cytology / Q000276:immunology* / Q000473:pathology / Q000821:virology; D051379:Mice; D008822:Mice, Transgenic; D011498:Protein Precursors / Q000378:metabolism; D014162:Transfection; D014758:Viral Core Proteins / Q000378:metabolism
D001323:Autoantibodies; D006510:Hepatitis B Antibodies; D006513:Hepatitis B e Antigens; D016898:Interferon-alpha; D011498:Protein Precursors; D014758:Viral Core Proteins; D007371:Interferon-gamma