Urine levels of CD46 (membrane cofactor protein) are increased in patientswith glomerular diseases

Soluble membrane cofactor protein (MCP, CD46) has not been detected by conv entional ELISA in human urine. Here, we established a highly sensitive assa y method for determination of urinary MCP (uMCP) using monoclonal antibody- coated paramagnetic beads. This method enabled us to detect less than 0.05 ng/ml of purified membrane and recombinant soluble MCP, a sensitivity 10-fo ld higher than that of conventional ELISA. In normal subjects, the levels o f uMCP were <0.05 ng/ml, The levels of uMCP were elevated in patients with IgA nephropathy and more prominently in patients with rapidly progressive g lomerulonephritis. The levels of uMCP were correlated significantly with th ose of serum MCP (sMCP) and N-acetyl-beta-glucosaminidase and nonsignifican tly with those of beta(2)-microglobulin, total urine protein, or serum crea tinine. The properties of uMCP were inconsistent with those of the reported sMCP, since uMCP showed three bands on SDS-PAGE/immunoblotting with molecu lar mass profiles different from those of sMCP. uMCP exhibited factor I cof actor activity for cleavage of C3b comparable to that of sMCP. The origin o f uMCP, however, remains to be determined, These results, taken together wi th the parameter correlation profiles, suggested that uMCP is secreted or p roduced secondary to tubular or glomerular damage. The physiological role a nd clinical significance of uMCP are now within the scope of our investigat ion by establishment of this assay. (C) 2000 Academic Press.