Antibodies to human albumin in cirrhotic sera.

In a previous paper we described a monoclonal IgM protein with antibody-like activity towards aggregated and native albumin. The present study was initiated to determine whether sera, other than that from patients with macroglobulinemia, contained similar antibody-like activity. It was demonstrated that approximately 40% of the sera from patients with classical Laennec's cirrhosis contained antibodies which agglutinate sheep red blood cells coated with aggregated albumin. The hemagglutinating activity was present in the void volume on Sephadex G-200 chromatography and was shown to be an immunoglobulin by its removal on passage over an anti-L-chain immunoadsorbent column. The immunoglobulin was isolated from cirrhotic sera by chromatography on an albumin immunoadsorbent column. The acid eluate from the albumin affinity column contained only IgA. After labeling this IgA with (125)I and obtaining the Fabalpha fragment by proteolysis, it was shown that the labeled Fabalpha complexed noncovalently with aggregated albumin. Complex formation between albumin and the cirrhotic IgA and Fabalpha could also be demonstrated utilizing facilitation of hemagglutination of sheep red blood cells coated with aggregated albumin. Appropriate controls consisting of normal and myeloma IgA and myeloma Fabalpha fragments failed to show evidence of complex formation with albumin. We propose that the restriction of the antibody response to the IgA class may result from the formation of antibodies against albumin altered during metabolism in the gastrointestinal tract. A possible role for anti-albumin antibodies in normal albumin catabolism and in the pathogenesis of Laennec's cirhosis is discussed.