Serial study of liver-directed autoantibodies and autoreactive T-lymphocytes in acute viral hepatitis B.
To explore the mechanisms underlying liver-directed autoimmune reactions in acute Hepatitis B Virus (HBV) infection, we followed five subjects who were identified in the early incubation phase (30-70 days before the first elevation of transaminases). We assessed serially cellular (using a T-lymphocyte migration inhibitory factor assay) and humoral (RIA) immunity to LSP (a macromolecular, liver-derived lipoprotein complex) and hepatic lectin (HL), the liver-specific receptor for desialylated glycoproteins, which appears to be a major target antigen for autoreactions in autoimmune chronic active hepatitis. Anti-LSP and anti-HL autoantibodies were found, at some stage during acute HBV infection, in 4/5 subjects, whereas cellular immunity to the same antigens was detected in only two patients. Sustained production of anti-HL antibodies was noted only in patients showing cellular immunity to this antigen and was apparently secondary to liver damage, whereas anti-LSP antibodies were first detected at the onset of liver injury when there was no evidence of T-cell immunity to the same antigenic complex. One explanation for this apparent dichotomy between cellular and humoral responses to LSP is that a helper T-cell response to the major envelope component of HBV, HBsAg, which precedes by 10-20 days the development of anti-LSP antibodies, promotes a humoral reaction to autoantigens contained in the LSP preparation, coexpressed with HBsAg, on the surface of infected hepatocytes.
Vento
S
S
Liver Unit, King's College School of Medicine and Dentistry, London, UK.
McFarlane
B M
BM
Vento
T G
TG
Ranieri
S
S
Rondanelli
E G
EG
McFarlane
I G
IG
Williams
R
R
Eddleston
A L
AL
D000293:Adolescent; D000328:Adult; D037263:Asialoglycoprotein Receptor; D001323:Autoantibodies / Q000032:analysis*; D005260:Female; D006509:Hepatitis B / Q000150:complications / Q000276:immunology*; D006511:Hepatitis B Antigens / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D007961:Leukocyte Migration-Inhibitory Factors / Q000032:analysis; D008099:Liver / Q000276:immunology*; D008297:Male; D008565:Membrane Proteins; D011506:Proteins / Q000276:immunology; D011971:Receptors, Immunologic / Q000276:immunology; D013601:T-Lymphocytes / Q000502:physiology; D000637:Transaminases / Q000097:blood
D037263:Asialoglycoprotein Receptor; D001323:Autoantibodies; D006511:Hepatitis B Antigens; D007961:Leukocyte Migration-Inhibitory Factors; D008565:Membrane Proteins; D011506:Proteins; D011971:Receptors, Immunologic; D000637:Transaminases