Variable expression of heparan sulfate epitopes in crescents of human glomerulonephritis

Crescentic glomerulonephritis leads to a rapid loss of renal function. Alth ough glomerular crescents are rich in extracellular matrix (ECM), the compo sition and genesis of the ECM are incompletely understood. Heparan sulfate (HS) is a major ECM molecule and has polymeric structure of great variabili ty. Recent findings that alterations in HS epitopes are associated with ren al pathology prompted us to hypothesize that specific HS epitopes might be expressed in the evolution of crescents. We reviewed clinical records of 72 4 patients who underwent renal biopsy and found 21 patients with rapidly pr ogressive glomerulonephritis. Immunohistochemistry was performed using mono clonal antibodies (mAbs) against well-defined HS epitopes, One mAb was dire cted against unsaturated uronic acid residues generated during the selectiv e removal of HS by heparitinase (a), and a further two different mAbs again st N-sulfate-enriched and O-sulfate-poor portions of HS (b). Results showed that mAb (a) reacted to ECM of normal, sclerosed and crescentic glomeruli and that mAbs (b) reacted strongly to ECM of fibrocellular crescents but no t to fibrous crescents, the periglomerular areas and noncrescentic intraglo merular areas, We concluded there are regional differences in HS epitope ex pression, although HS are ubiquitous components of glomerular ECM. N-sulfat e-enriched and O-sulfate-poor portions of HS might play a role in crescent formation.