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 37ยฐC 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, 26 patients with alcoholic liver disease were studied. Using sucrose density gradient fractionation followed by quantitation of IgG by radioimmunoassay, high molecular weight IgG complexes (>llS) were frequently present in alcoholic liver disease sera, and correlated with the degree of hypergammaglobulinemia and/or hypoalbuminemia, and with '261-C l q 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.
Previous investigators have reported the frequent presence of circulating immune complexes (ICs) in alcoholic liver disease (ALD) (1-3). Specific antibodies to alcoholic hyaline, polymeric albumin, DNA, and other cellular constituents have been detected in sera from patients with ALD (4-7), raising the possibility that these antibodies could be involved in IC formation. Despite this, attempts to isolate a specific IC-associated antigen have been unsuccessful. Therefore, the nature and pathogenic significance of these presumed ICs in ALD remains to be defined.
The presence of circulating immunoglobulin aggregates in disease states has been previously suggested (โฌ9, although not confirmed. It is known that the available IC assays do not distinguish immunoglobulin aggregates from true antigen-antibody complexes. In addition, in vitro experiments have demonstrated spontaneous immunoglobulin aggregate formation at 37ยฐC in the pres- ence of hypergammaglobulinemia and/or hypoalbuminemia (9). These conditions are characteristic of chronic parenchymal liver disease, including ALD, and could predispose to aggregate formation in viuo. Based on these