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C5b-9 and adhesion molecules in human idiopathic membranous nephropathy
Aikaterini A Papagianni1, Efstathios Alexopoulos, Maria Leontsini
1Department of Nephrology, Hippokration General Hospital, 50 Papanastasiou Str. 54642 Thessaloniki, Greece. aikpapag@otenet.gr
Background:
Cellular immune responses and C5b-9 seem to play an important role in the pathogenesis and progression of idiopathic membranous nephropathy (IMN). The aim of the study was to investigate the role of C5b-9 and adhesion molecules in the pathogenesis of the disease.
Methods:
The clinical and pathological data of 35 patients with biopsy-proven IMN were correlated with immunohistochemical findings using monoclonal antibodies against T lymphocytes, monocytes/macrophages (MM), HLA-DR antigens, C5b-9, and adhesion molecules such as alpha3beta1, LFA-1beta, and ICAM-1.
Results:
In the glomeruli, C5b-9 deposits showed a significant correlation with the intensity of IgG and C3 deposition. The stage of the disease had a significant negative relationship with the glomerular alpha3beta1 expression. In the tubulointerstitium (TIN), the number of HLA-DR(+) cells was highly correlated with the numbers of total T lymphocytes, MM, and LFA-1beta(+) cells, as well as with the percentage of tubules with C5b-9 deposits. The extent of ICAM-1 expression in the TIN was significantly correlated with the numbers of interstitial MM, HLA-DR(+), and LFA-1beta(+) cells, as well as with the extent of tubular C5b-9 deposition. The severity of tubular atrophy and interstitial fibrosis had a relationship with the numbers of total T lymphocytes, MM, HLA-DR(+), and LFA-1beta(+) cells and with the extent of tubular C5b-9 deposition and ICAM-1 expression in the TIN. Serum creatinine (Scr) was highly correlated with the numbers of interstitial total T lymphocytes, MM, HLA-DR(+), and LFA-1beta(+) cells. Moreover, Scr had a significant relationship with the severity of tubular atrophy and interstitial fibrosis, as well as with the extent of tubular C5b-9 deposition and ICAM-1 expression in the TIN. Proteinuria was significantly correlated with the extent of tubular alpha3beta1 expression.
Conclusions:
In IMN, C5b-9 formation may be secondary to IgG and C3 deposition. Proteinuria may contribute to the TIN damage by altering the expression of alpha3beta1 integrins in tubular cells. De novo ICAM-1 and C5b-9 expression within the TIN as well as the activated interstitial cells may be important factors leading to renal damage and renal function impairment.