title: Monomeric immunoglobulin A protects glomerulus against polymeric immunoglobulin A immune complex in experimental immunoglobulin A nephropathy.
abstract: Polymeric (p) IgA constitutes 13% of total serum IgA, whereas monomeric (m) IgA represents the other 87%. pIgA tends to form complexes in the circulation that eventually localize in the glomerulus. mIgA is a nonprecipitable antibody. When complexed with an antigen in vivo, the circulating mIgA immune complex (IC) thus formed does not deposit in the glomerulus. The purpose of the present study was to evaluate the influence of mIgA on the formation of pIgA-lC and subsequent glomerular deposition of the IC in an experimental model of IgA nephropathy. The influence of mIgA anti-dinitrophenyl (DNP) on pIgA anti-DNP/DNP-conjugated BSA (BSA-DNP) IC formation was assessed by double diffusion test and competition PAGE in combination with autoradiography. Only the BSA-DNP, a model antigen of relatively low molecular mass, was radiolabeled and monitored throughout the latter experiment. An analysis of clearance kinetics (1 and 6 hours) of the antigen using 4-week-old female BALB/c mice, and a series of renal studies were performed after intravenous injection with a single dose of combined pIgA anti-DNP, BSA-DNP, and mIgA anti-DNP. As demonstrated by the double diffusion test, addition of mIgA anti-DNP resulted in suppression of the precipitating reaction of pIgA anti-DNP and BSA-DNP. This effect was confirmed by PAGE for size determination of the BSA-DNP which had been complexed with either pIgA anti-DNP or a mixture of pIgA anti-DNP and mIgA anti-DNP. The clearance kinetics studies showed that the elimination of BSA-DNP injected with pIgA anti-DNP was prolonged in the presence of mIgA anti-DNP in a partially dose-dependent manner. The experimental mice receiving pIgA anti-DNP, BSA-DNP, and mIgA anti-DNP showed less hematuria (p < 0.005) than mice receiving pIgA anti-DNP and BSA-DNP (positive control) when examined 1 hour after injection. Immunofluorescence study of the renal tissue of mice receiving pIgA anti-DNP, BSA-DNP, and mIgA anti-DNP showed a suppressed glomerular localization of IgA and third component of complement, as compared with those injected with pIgA anti-DNP and BSA-DNP alone. Similarly, a significant decrease of glomerular BSA-DNP deposits was observed in mice receiving pIgA anti-DNP, BSA-DNP, and mIgA anti-DNP compared with those receiving pIgA anti-DNP and BSA-DNP alone, as demonstrated by light microscopic autoradiography. These findings indicate that a high dose of specific mIgA was capable of modulating glomerular deposition of the pIgA-IC in this animal model of IgAN.
authors.affiliation: Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Republic of China.
authors.forename: A
authors.initials: A
authors.lastname: Chen
authors.forename: L F
authors.initials: LF
authors.lastname: Sheu
authors.forename: S L
authors.initials: SL
authors.lastname: Ding
authors.forename: W H
authors.initials: WH
authors.lastname: Lee
mesh_terms: D000818:Animals; D000936:Antigen-Antibody Complex / Q000378:metabolism*; D005260:Female; D005922:Glomerulonephritis, IGA / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D007070:Immunoglobulin A / Q000378:metabolism* / Q000627:therapeutic use*; D007678:Kidney Glomerulus / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C
chemical_list: D000936:Antigen-Antibody Complex; D007070:Immunoglobulin A; C034639:polymeric IgA