Evidence Against an Immune Complex Pathogenesis of Primary Biliary Cirrhosis

Abstract

In an attempt to confirm the presence of immune complexes in the sera of patients with primary biliary cirrhosis, sera of patients with primary biliary cirrhosis were studied with four sensitive radioimmunoassays. Thirty-one sera from 27 patients with well-characterized primary biliary cirrhosis, stages 1–4, were negative for immune complexes using three assays, the monoclonal rheumatoid factor inhibition assay, the C1q binding inhibition assay, and the C1q solid-phase assay. Nine of 31 sera were weakly positive with the C1q binding assay. Attempts at confirming the presence of immune complexes in sera positive in the C1q binding assay were unsuccessful because none of the sera were sufficiently positive for the reactant to be studied after fractionation. The positivity in the C1q binding assay was not due to greater sensitivity of that assay. Two assays used, the monoclonal rheumatoid factor binding inhibition assay and the C1q solid-phase assay, were 2–3 times more sensitive than the C1q binding assay. Neither could the negative results be explained by processing or storage artifacts because immediate assays of freshly drawn sera were also negative. There were no inhibitors of immune complex assays in our primary biliary cirrhosis sera. The addition of primary biliary cirrhosis sera that were negative for immune complexes to lupus serum did not inhibit the detection of immune complexes in lupus serum. To eliminate the likelihood that our negative results were due to some unrecognized methodologic problem in our own laboratory, we sent 25 primary biliary cirrhosis sera to an independent laboratory that used the Raji cell assay. Twenty-two of 25 sera were negative. In addition, at least one-third of the serum reactivity in the three positive sera was due to substances other than immune complexes. The data strongly suggest that circulating immune complexes are not involved in the pathogenesis of primary biliary cirrhosis.