Expression of glomerular heparan sulphate domains in murine and human lupus nephritis.
SourceNephrology, Dialysis, Transplantation, 22, 7, (2007), pp. 1891-902
Article / Letter to editor
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Paediatrics - OUD tm 2017
Nephrology, Dialysis, Transplantation
SubjectIGMD 3: Genomic disorders and inherited multi-system disorders; IGMD 8: Mitochondrial medicine; IGMD 9: Renal disorder; N4i 4: Auto-immunity, transplantation and immunotherapy; NCMLS 1: Immunity, infection and tissue repair; NCMLS 1: Infection and autoimmunity; NCMLS 3: Tissue engineering and pathology; NCMLS 4: Energy and redox metabolism; ONCOL 3: Translational research; UMCN 5.4: Renal disorders
BACKGROUND: Recently, we identified specific N- and 6-O-sulphated heparan sulphate (HS) domains on activated glomerular endothelial cells. In this study, we evaluated in lupus nephritis the expression of different HS domains on glomerular endothelium and in the glomerular basement membrane (GBM). METHODS: The expression of specific glomerular HS domains and the presence of immunoglobulins (Ig) were determined by immunofluorescence staining of kidney sections of patients with nephritis due to systemic lupus erythematosus (SLE) and MRL/lpr lupus mice. The expression/presence of glomerular HS domains and Ig was also evaluated after eluting Ig from renal sections of lupus mice using two elution methods, and in renal sections of lupus mice treated with heparinoids. RESULTS: Both MRL/lpr mice and patients with lupus nephritis showed a decreased expression of HS in the GBM. The expression of N- and 6-O-sulphated HS domains on glomerular endothelium was decreased in MRL/lpr mice, but increased in SLE patients. MRL/lpr mice had more extensive glomerular Ig deposits than SLE patients. After elution of Ig, the glomerular endothelial expression of N- and 6-O-sulphated HS domains in MRL/lpr mice was recovered and even increased above normal levels, while the expression of HS in the GBM was restored to normal levels. Treatment with heparinoids prevented Ig deposition and preserved the expression of glomerular HS domains at normal levels in lupus mice. CONCLUSION: The expression of specific HS domains on glomerular endothelium and in the GBM is changed during lupus nephritis due to masking by Ig deposits and induction of inflammatory N- and 6-O-sulphated HS domains.
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