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

Background. Henoch-Schonlein purpura is a common vasculitis of childhood af fecting the skin, joints, gastrointestinal tract, and kidney. The mesangial deposition of IgAl is the most critical factor for the prognosis of patien ts with this disease. The aberrant glycosylation of the IgAl subclass with the absence of terminally located galactose and presence of only alpha-N-ac etylgalactosamine in O-linked oligosaccharides in the hinge region of IgAl represents a prominent difference from the normal IgAl. These alterations p rompt the supposition that the sugar part may guide IgA deposition by recog nition of endogenous lectins on the mesangium. Methods. Owing to the limited knowledge about the expression of carbohydrat e-binding sites in the human kidney we initiated the study of this aspect w ith a class of tools which are suitable to map the lectinome of cells. Empl oying biotinylated neoglycoconjugates, glycosaminoglycans, and sulphated po lysaccharides we monitored the presence of accessible carbohydrate-binding sites in control kidneys represented by tumour-free areas of kidneys with G rawitz tumour and in biopsies from patients with Henoch-Schonlein purpura-a ssociated IgA nephropathy. Results. Using frozen sections, no expression of any tested carbohydrate-bi nding site(s) was observed in the endothelial and the mesangial cells in gl omeruli of the control kidneys as well as in the biopsies from Henoch-Schon lein purpura IgA nephropathic kidneys, in contrast to the tubules. The N-ac etylgalactosamine-binding sites were expressed only in the inner layer of B owman's capsule of 20% of glomeruli of the control kidney from one patient with Grawitz tumour and one biopsy from a patient with Henoch-Schonlein pur -pura-associated IgA nephropathy. However, the macrophages in the glomeruli of patients with IEA nephropathy and interstitial macrophages from both st udied groups, i.e. without and with IgA nephropathy, harbour capacity to re cognize carrier-immobilized alpha-N-acetylgalactosamine. Access to this bin ding site for the neoligand conjugate can be blocked by the monoclonal anti body MEM-18 recognizing CD14 antigen. Conclusion. The possibility for a participation of macrophage deposition of IgAl in mesangium via a lectin mechanism involving this binding capacity w arrants further studies.