Glomerular deposition of immune complexes prepared with monomeric or polymeric IgA.

Abstract

Clearance kinetics and renal deposition of soluble IgA immune complexes (IgA IC) were examined to determine the nephritogenic potential of IgA molecular form in mediating experimental IgA nephropathy. The immune complexes were prepared by mixing purified radiolabelled monomeric (mIgA) or polymeric (pIgA) IgA anti-dinitrophenyl (DNP), derived from MOPC-315 myeloma, with DNP conjugated Ficoll (DNP8-Ficoll). Clearance of IgAIC from the circulation was curve fitted by two exponential components. The first component was similar for both mIgA IC and pIgA IC. The second component was slightly more rapid for mIgA IC than for pIgA IC. Immunofluorescence studies, however, showed that only pIgA IC deposited in the kidneys. Analysis of IgA IC by gradient polyacrylamide gel electrophoresis indicated that mIgA formed only small latticed complexes. The critical role of IgA IC lattice size in renal deposition was confirmed by demonstrating that large latticed mIgA IC, prepared by covalent cross-linking mIgA with a specific affinity labelling antigen, deposited in the kidneys in a pattern similar to pIgA IC. Our results suggest that the monovalency of mIgA is responsible for its inability to form a large latticed nephritogenic complexes.