Effect of antibody charge and concentration on deposition of antibody to glomerular basement membrane

MP Madaio, DJ Salant, S Adler, C Darby, WG Couser - Kidney international, 1984 - Elsevier
MP Madaio, DJ Salant, S Adler, C Darby, WG Couser
Kidney international, 1984Elsevier
Effect of antibody charge and concentration on deposition of antibody to glomerular
basement membrane. Fixed anionic sites within the glomerular capillary wall influence the
permeation of serum proteins, the localization of various antigens, and the deposition of
antibody in the subepithelial space. In anti-GBM nephritis antibody deposition occurs very
rapidly to antigenic sites located relatively proximal in the glomerular capillary wall. We
examined the influence of the glomerular charge barrier on anti-GBM antibody deposition by …
Effect of antibody charge and concentration on deposition of antibody to glomerular basement membrane. Fixed anionic sites within the glomerular capillary wall influence the permeation of serum proteins, the localization of various antigens, and the deposition of antibody in the subepithelial space. In anti-GBM nephritis antibody deposition occurs very rapidly to antigenic sites located relatively proximal in the glomerular capillary wall. We examined the influence of the glomerular charge barrier on anti-GBM antibody deposition by comparing the rate of deposition of antibodies with cationic and anionic isoelectric points. Purified sheep anti-rat GBM IgG was isolated from acid eluates of kidneys obtained 24 hr after rats were injected with sheep antiserum to rat GBM. Anti-GBM IgU was separated into cationic (p1 6.4—8.5) and anionic (p1 4.2—6.8) fractions, which were radiolabelled with 131j and 1251, respectively, shown to have equal antibody contents measured by in vitro binding to normal glomeruli, mixed in equal amounts, and injected in incremental doses to ten rats. At 1 hr the glomerular antibody binding of each fraction was directly related to the blood level (r= 0.95, r= 0.97) and delivery of antibody (r= 0.98, r= 0.98). Glomerular binding of cationic antibody was four times greater than anionic antibody over the entire range of deliveries studied (P< 0.001). We conclude that glomerular deposition of anti-GBM antibody is directly related to blood concentration and delivery of antibody. Furthermore, the deposition of cationic antibodies to GBM antigens was significantly greater than the deposition of anionic antibodies. The charge-selective glomerular filtration barrier may be an important determinant of the quantity and subclass composition of anti-GBM lgG deposits in glomeruli, and therefore of the severity of tissue injury produced.
Effet de Ia charge et de Ia concentration d'un anticorps sur le dépôt d'anticorps sur Ia membrane basale glomerulaire. Les sites anioniques fixes dans Ia paroi capillaire glomërulaire influencent le passage des protéines sériques, Ia localisation de divers antigènes et le dépôt d'anticorps dans l'espace sousépithélial. Dans Ia néphrite a anti-GBM, le depot d'anticorps survient très rapidement sur des sites antigéniques situés de facon relativement proximate dans la paroi capillaire glomerulaire. Nous avons examine l'influence de Ia barrière de charge glomerulaire sur de depot d'anticorps anti-GBM en comparant la vitesse de depot d'anticorps avec des points isoélectriques cationiques ou anioniques. De l'IgG purifiée de mouton anti-GBM de rat a Cté isolée a partir d'éluats acides de reins obtenus 24 heures aprés que les rats aient recu des injections d'antisérum de mouton contre Ia GBM de rat. Les lgG anti-GBM ont été séparées en fractions cationiques (p1 6, 4—8, 5) et anioniques (p1 4, 2—6, 8) qui ont été radiomarquees avec 1311 et 1251,
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