title: Lack of complement activation by human IgA immune complexes.
abstract: Complement activation may play an important role in renal injury associated with glomerular deposition of IgA immune complexes. The ability of naturally occurring human IgA immune complexes (IgA-IC) and covalently cross-linked human IgA oligomers (X-IgA) to activate complement were examined in vitro and in vivo. Large-sized IgA-IC were isolated from a patient's serum by affinity purification (Jacalin-Sepharose) and gel chromatography. Stable X-IgA were prepared by chemical cross-linking with a heterobifunctional reagent, N-succinimdyl 3-(2-pyridyl-dithio) propionate (SPDP). Treatment of fresh normal human serum with large amounts of either IgA-IC or X-IgA failed to activate C3. The C3 consumption was measured immunochemically by the decrease of the B antigen on the native C3 and by the generation of iC3b. Addition of these complexes to serum did not result in cleavage of factor B. Administration of human IgA-IC or X-IgA to mice, killed after 6 h, resulted in glomerular deposition of IgA. Despite the presence of intense glomerular IgA deposits no C3 was detected. Collectively, these findings suggest that neither soluble nor renal localized human IgA complexes activate complement.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Texas Health Science Center, Houston.
authors.forename: H
authors.initials: H
authors.lastname: Imai
authors.forename: A
authors.initials: A
authors.lastname: Chen
authors.forename: R J
authors.initials: RJ
authors.lastname: Wyatt
authors.forename: A
authors.initials: A
authors.lastname: Rifai
mesh_terms: D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology*; D003167:Complement Activation; D003176:Complement C3 / Q000378:metabolism; D011415:Complement Factor B / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D005922:Glomerulonephritis, IGA / Q000276:immunology; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology* / Q000378:metabolism; D007678:Kidney Glomerulus / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged
chemical_list: D000936:Antigen-Antibody Complex; D003176:Complement C3; D007070:Immunoglobulin A; D011415:Complement Factor B