Evidence against an immune complex pathogenesis of primary biliary cirrhosis
Goldberg, M.J.; Kaplan, M.M.; Mitamura, T.; Anderson, C.L.; Matloff, D.S.; Pinn, V.W.; Agnello, V.
Gastroenterology 83(3): 677-683
1982
ISSN/ISBN: 0016-5085 PMID: 6212278 Document Number: 183766
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 4 sensitive radioimmunoassays. Sera (31) from 27 patients with well-characterized primary biliary cirrhosis, stages 1-4, were negative for immune complexes using 3 assays, the monoclonal rheumatoid factor inhibition assay, the C1q [complement component 1q] 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 to 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. The negative results could not 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 the 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 the negative results were due to some unrecognized methodologic problem in the laboratory, 25 primary biliary cirrhosis sera were sent to an independent laboratory that used the Raji cell assay. Of 25 sera, 22 were negative. At least 1/3 of the serum reactivity in the 3 positive sera was due to substances other than immune complexes. Circulating immune complexes are apparently not involved in the pathogenesis of primary biliary cirrhosis.