Binding sites for carrier-immobilized carbohydrates in the kidney: implication for the pathogenesis of Henoch-Schönlein purpura and/or IgA nephropathy.

Abstract

BACKGROUND:

Henoch-Schönlein purpura is a common vasculitis of childhood affecting the skin, joints, gastrointestinal tract, and kidney. The mesangial deposition of IgA1 is the most critical factor for the prognosis of patients with this disease. The aberrant glycosylation of the IgA1 subclass with the absence of terminally located galactose and presence of only alpha-N-acetylgalactosamine in O-linked oligosaccharides in the hinge region of IgA1 represents a prominent difference from the normal IgA1. These alterations prompt the supposition that the sugar part may guide IgA deposition by recognition of endogenous lectins on the mesangium.

METHODS:

Owing to the limited knowledge about the expression of carbohydrate-binding sites in the human kidney we initiated the study of this aspect with a class of tools which are suitable to map the lectinome of cells. Employing biotinylated neoglycoconjugates, glycosaminoglycans, and sulphated polysaccharides we monitored the presence of accessible carbohydrate-binding sites in control kidneys represented by tumour-free areas of kidneys with Grawitz tumour and in biopsies from patients with Henoch-Schönlein purpura-associated IgA nephropathy.

RESULTS:

Using frozen sections, no expression of any tested carbohydrate-binding site(s) was observed in the endothelial and the mesangial cells in glomeruli of the control kidneys as well as in the biopsies from Henoch-Schönlein purpura IgA nephropathic kidneys, in contrast to the tubules. The N-acetylgalactosamine-binding sites were expressed only in the inner layer of Bowman's capsule of 20% of glomeruli of the control kidney from one patient with Grawitz tumour and one biopsy from a patient with Henoch-Schönlein purpura-associated IgA nephropathy. However, the macrophages in the glomeruli of patients with IgA nephropathy and interstitial macrophages from both studied groups, i.e. without and with IgA nephropathy, harbour capacity to recognize carrier-immobilized alpha-N-acetylgalactosamine. Access to this binding site for the neoligand conjugate can be blocked by the monoclonal antibody MEM-18 recognizing CD14 antigen.

CONCLUSION:

The possibility for a participation of macrophage deposition of IgA1 in mesangium via a lectin mechanism involving this binding capacity warrants further studies.

• Authors: A Sedivá, K Smetana Jr, J Stejskal, J Bartůnková, F T Liu, N V Bovin, H J Gabius
• Journal: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association (Nephrol Dial Transplant) Vol. 14 Issue 12 Pg. 2885-91 (Dec 1999) ISSN: 0931-0509 [Print] England
• PMID: 10570092 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Immunoglobulin A
• Lipopolysaccharide Receptors
• Acetylgalactosamine

Topics

• Acetylgalactosamine (metabolism)
• Binding Sites
• Carbohydrate Metabolism
• Glomerulonephritis, IGA (etiology)
• Humans
• IgA Vasculitis (etiology)
• Immunoglobulin A (metabolism)
• Kidney (metabolism)
• Lipopolysaccharide Receptors (metabolism)