Enzymatically deglycosylated human IgA1 molecules accumulate and induce inflammatory cell reaction in rat glomeruli.
BACKGROUND
Previously, we have been able to isolate IgA1 from IgA nephropathy (IgAN) patients, that could accumulate in rat glomeruli (glomerulophilic IgA1). The 'glomerulophilic IgA1' was determined to be under-O-glycosylated in its hinge region, suggesting that under-O-glycosylation in the IgA1 hinge region plays a role in its glomerular deposition in IgAN. To confirm this, the accumulation of enzymatically under-glycosylated IgA1 in rat kidney was examined.


METHODS
Human IgA1 was isolated from healthy individuals by Jacalin-affinity chromatography. Desialylated (deS IgA1) or further degalactosylated IgA1 (deS/deGal IgA1) molecules were then prepared using neuraminidase and beta-galactosidase. Two or five mg of IgA1 were injected into the left renal artery of Wistar rats. The rats were sacrificed at various time intervals (3, 9, 24 h) and the perfused part of the renal cortex was removed for immunofluorescence and for light and electron microscopy.


RESULTS
Distinct amounts of deS IgA1 and deS/deGal IgA1 were observed in rat glomeruli. On the other hand, untreated IgA1 molecules (native IgA1) did not show any obvious accumulation. In rats injected with under-glycosylated IgA1, accumulation of polymorphonuclear cells (PMN) was also observed.


CONCLUSIONS
These results confirmed that under-glycosylation of IgA1 played an important role in the glomerular accumulation of IgA1, which was followed by infiltration of PMN into glomeruli.
Sano
Takashi
T
School of Medicine, Kitasato University, 1-15-1 Kitasato, Sagamihara-city, Kanagawa 228-8555, Japan.
Hiki
Yoshiyuki
Y
Kokubo
Tohru
T
Iwase
Hitoo
H
Shigematsu
Hidekazu
H
Kobayashi
Yutaka
Y
D000818:Animals; D005260:Female; D005922:Glomerulonephritis, IGA / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000378:metabolism* / Q000473:pathology; D009504:Neutrophils / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
D007070:Immunoglobulin A