The Nature of IgG Complexes in Alcoholic Liver Disease

Circulating immune complexes have been described in most liver diseases, including alcoholic liver disease, although their pathogenic significance remains unclear. Currently available immune complex assays do not distinguish immunoglobulin aggregates from antigen‐antibody complexes. Immunoglobulin aggregate formation occurs in vitro at 37°C in the presence of hypergammaglobulinemia and/or hypoalbuminemia, conditions common in liver disease. To determine if hypergammaglobulinemia and/or hypoalbuminemia could predispose to immunoglobulin aggregate formation in vivo, 25 patients with alcoholic liver disease were studied. Using sucrose density gradient fractionation followed by quantitation of IgG by radioimmunoassay, high molecular weight IgG complexes (>11S) were frequently present in alcoholic liver disease sera, and correlated with the degree of hypergammaglobulinemia and/or hypoalbuminemia, and with ¹²⁵I‐Clq binding activity. Sodium dodecyl sulfate‐polyacrylamide gel electrophoresis analysis of these complexes revealed only IgG and nonspecific trapping of several normal serum proteins. A specific complex‐associated antigen could not be identified. While small, undetectable quantities of true antigen‐antibody complexes might also be present, our data suggest that IgG complexes in alcoholic liver disease may represent immunoglobulin aggregate formation in vivo.