Glomerular immune deposits in experimental IgA nephropathy. A continuum of circulating and in situ formed immune complexes.
Studies were undertaken to elucidate the primary pathogenetic mechanisms responsible for immunoglobulin (Ig) A immune complexes formation and glomerular deposition in vivo. Monomeric (mIgA) and polymeric IgA (pIgA) anti-dinitrophenyl (DNP) were purified from MOPC 315 myeloma. A DNP-conjugated Ficoll was used as an antigen. For simulation of natural conditions of in vivo immune complex formation, 131I-DNP-Ficoll and 125I-IgA were administered through the intravenous and intraperitoneal routes, respectively. The kinetics half-life (t1/2) of the antigen (2.9 hours) and either the pIgA (7.2 hours) or mIgA (6.3 hours) in the experimental groups was not significantly different from the control. Glomerular IgA immune deposits were detectable only in mice that received pIgA and DNP-Ficoll. Plasma samples analyzed by gradient polyacrylamide gel electrophoresis revealed formation of large- and intermediate-sized pIgA complexes in circulation prior to glomerular deposition. Although mIgA failed to interact with such complexes in the circulation, it did bind to the pIgA immune deposits in the glomerulus. These results indicate that glomerular IgA immune deposits evolve from the localization of preformed circulating pIgA complexes that eventuates an in situ mIgA-mediated complex formation.
Chen
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Department of Pathology and Laboratory Medicine, University of Texas Health Science Center at Houston.
Wong
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Rifai
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D000818:Animals; D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex / Q000032:analysis*; D004195:Disease Models, Animal; D005260:Female; D005455:Fluorescent Antibody Technique; D005922:Glomerulonephritis, IGA / Q000276:immunology / Q000473:pathology*; D007070:Immunoglobulin A / Q000032:analysis; D007678:Kidney Glomerulus / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D007070:Immunoglobulin A