Patients with primary biliary cirrhosis have a defect in the receptor mediated clearance of complement coated erythrocytes by fixed macrophages of the reticuloendothelial system. To investigate the probable mechanism of this defect peripheral blood monocytes were isolated from nine patients with primary biliary cirrhosis and seven control subjects and the ability of these cells to form rosettes with complement coated, IgM-sensitised sheep erythrocytes was assessed. Primary biliary cirrhosis peripheral blood monocytes formed rosettes to the same extent as control peripheral blood monocytes (71.0 +/- 7.1% [SEM] versus 73.3 +/- 4.3%) suggesting normal complement receptor function of primary biliary cirrhosis peripheral blood monocytes. When primary biliary cirrhosis or control peripheral blood monocytes were preincubated with primary biliary cirrhosis serum, however, the per cent of peripheral blood monocytes that formed rosettes was decreased: 2.4 +/- 0.8 and 3.1 +/- 1.3 fold respectively. To study this phenomenon further, fractions containing IgG or IgM synthesised by cultures of control or primary biliary cirrhosis lymphocytes were prepared. Rosette formation was not affected by exposure to fractions containing control or primary biliary cirrhosis IgG or control IgM, but was markedly inhibited (6.0 +/- 4.8 fold) by exposure to fractions containing primary biliary cirrhosis IgM. Similar results were obtained when freshly isolated peripheral blood monocytes or peripheral blood monocytes that had been cultured for 7-10 days--that is, macrophages, were used. Assuming that one can draw inferences concerning the status of fixed macrophages from data obtained using peripheral blood monocytes, the results of this study suggest that the complement specific defect in reticuloendothelial system clearance function in primary biliary cirrhosis is not caused by abnormality in the functional status of complement receptors on fixed macrophages but rather by a factor present in the serum of patients with primary biliary cirrhosis that has the capacity to inhibit the adherence of complement coated erythrocytes to complement receptors present on the surface of fixed macrophages. This serum factor does not appear to be a complement component but rather a product of peripheral blood mononuclear cells, other than IgG.
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