Hepatic 60-kD heat-shock protein responses in alcoholic hepatitis.
The precise mechanism of the pathogenesis of alcoholic hepatitis is unknown, but immune involvement may perpetuate and exacerbate the process. Heat-shock proteins, normally protective, may be immunogenic and have been shown to induce antibody formation in some inflammatory conditions. Alcohol, cellular hypoxia and tumor necrosis factor, all involved in alcoholic hepatitis, are potent inducers of heat-shock protein. In this study, we sought 60-kD heat-shock protein in liver tissue with a murine monoclonal antibody and measured circulating antibody to 60-kD heat-shock protein on ELISA. Fourteen of 20 livers from patients with acute alcoholic hepatitis expressed 60-kD heat-shock protein in hepatocyte cytoplasm in a diffuse pattern with superimposed clusters; other cell types were occasionally positive. Twelve of these patients had high-titer IgA 60-kD heat-shock protein antibody in serum. In contrast, 60-kD heat-shock protein was identified in only 2 of the 10 patients with alcoholic cirrhosis without hepatitis (p = 0.013). These two patients had severe liver disease, and one patient in this group was seropositive for IgA 60-kD heat-shock protein antibody. Eight alcoholic patients with fatty liver alone were negative for antigen, and all but one were negative for antibody. The 10 patients without liver damage were negative for antigen and antibody. The findings that 60-kD heat-shock protein is present in liver tissue of patients with acute alcoholic liver damage and that circulating IgA 60-kD heat-shock protein antibody levels are increased may point to one pathogenetic mechanism underlying development and progression of liver damage in alcoholic hepatitis.
Institute of Liver Studies, King's College School of Medicine and Dentistry, London, United Kingdom.
J
J
Koskinas
V R
VR
Winrow
G L
GL
Bird
J Y
JY
Lau
B C
BC
Portmann
D R
DR
Blake
G J
GJ
Alexander
R
R
Williams
D000328:Adult; D000368:Aged; D003594:Cytoplasmic Granules / Q000378:metabolism; D005234:Fatty Liver / Q000378:metabolism / Q000473:pathology; D005260:Female; D006360:Heat-Shock Proteins / Q000276:immunology / Q000378:metabolism*; D006519:Hepatitis, Alcoholic / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007150:Immunohistochemistry; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008104:Liver Cirrhosis, Alcoholic / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged
D006360:Heat-Shock Proteins; D007070:Immunoglobulin A