Nephrol Dial Transplant (1999) 14: 2885-2891
© 1999 European Renal Association-European Dialysis and Transplant Association
Binding sites for carrier-immobilized carbohydrates in the kidney: implication for the pathogenesis of Henoch–Schönlein purpura and/or IgA nephropathy
edivá1
ina Bart
ková11 Institute of Immunology, 2nd Faculty of Medicine, Charles University, 2 Institute of Anatomy, 1st Faculty of Medicine, Charles University, 3 Institute of Pathology, 2nd Faculty of Medicine, Charles University, Prague, Czech Republic, 4 La Jolla Institute for Allergy and Immunology, San Diego, CA, USA, 5 Shemyakin Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia and 6 Institute for Physiological Chemistry, Faculty of Veterinary Medicine, Ludwig-Maximilians-University, Munich, Germany
Correspondence and offprint requests to:
Anna edivá, Institute of Immunology, 2nd Faculty of Medicine, Charles University, V úvalu 84, CZ-150 18 Prague 5, Czech Republic.
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 
-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 -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.
Keywords: -N-acetylgalactosamine; CD14; Henoch– Schönlein purpura; IgA nephropathy; lectin macrophage
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