Mixed cryoglobulinemia: Association of glomerulonephritis with defective reticuloendothelial system Fc receptor function

Although the etiology of mixed cryoglobulinemia is unknown, many of the symptoms appear to be representative of an immune complex-mediated disease. We have been interested in the pathophysiologic basis of immune complex disease and have begun to evaluate the functional status of the reticuloendothelial system (RES) in the removal of immune complexes from the circulation of patients with a number of types of autoimmune diseases. Studies by Mannik et al. in experimental animals have demonstrated that specific membrane receptors for the Fc portion of IgG play an important role in the removal of immune complexes from the circulation. We have developed methodology for the evaluation of RES Fc receptor functional activity in vivo in man, and in this report will present data which demonstrates that some patients with mixed cryoglobulinemia have marked defects in the functional activity of these reticuloendothelial system receptors. In addition, we have found that that there is a striking correlation of the clinical manifestations of disease with the clearance defect, but not with measurements of levels of immune complexes or the biological properties of the complexes, as evidenced by complement activation.