Clearance kinetics and fate of mouse IgA immune complexes prepared with monomeric or dimeric IgA.

Abstract

To determine the pathophysiologic mechanism(s) involved in experimental IgA nephropathy, the clearance kinetics and tissue distribution of soluble IgA immune complexes in mice were investigated. Purified radiolabeled dimeric (dIgA) and monomeric (mIgA) IgA antidinitrophenyl, obtained from MOPC-315, were covalently cross-linked with a bivalent affinity-labeling antigen, bis-2,4-dinitrophenyl pimelic ester. After i.v. injection, heavy polymers (greater than 1.2 X 10(6) m.w.) were rapidly removed from circulation. Analysis of circulating intermediate-latticed complexes by gradient polyacrylamide gel electrophoresis indicated that polymers with a minimal composition of four dIgA or eight mIgA were required for rapid elimination. The dIgA and mIgA complexes with lattices smaller than this critical size were removed at slower rates (yielding a t1/2 of 35 min for complexes with dIgA and a t1/2 of 60 min for complexes with mIgA). Tissue distribution of both dIgA and mIgA immune complexes was similar. The liver was the major organ involved in uptake of IgA immune complexes with an insignificant amount in the bile. Heavy polymers of dIgA or mIgA were predominantly localized in the hepatic nonparenchymal cells.