Role of Vascular Endothelial Growth Factor (VEGF) and B-Cell Lymphoma / Leukemia-2 (Bcl-2) in the Pathogenesis of Lupus Nephritis and Their Correlation to Clinicopathological Indices of Disease Activity.

作者:

Saeed AbdelHaleem SaadM. SalmanE. SeifMona A. Rafek

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摘要:

Serum concentrations of vascular endothelial growth factor(VEGF) and B cell lymphoma leukemia-2(Bcl-2) may be relevant in the pathogenesis and activity of lupus nephritis. Plasma concentrations of VEGF were found to be increased in patients with active lupus nephritis as a result of the presence of tissue hypoxia, inflammation and endothelial damage with disease activity. It was also over expressed in renal tissue from these patients. Serum levels of Bcl-2 were found to be elevated in patients with active lupus nephritis resulting in alteration in the process of apoptosis of T and B lymphocytes which may be related to the beginning of an autoimmune event that extends survival of B lymphocytes with breakdown of self-tolerance and increa sed production of pathogenic auto antibodies. A new biopsy index was modified from the standard National Institute of Health(NIH) activity index(AI) and chronicity index(CI) including: Glomerular activity index(GAI), Tubulointerstitial activity index(TIAI), Chronicity lesion index(CLI). Immunofluorescence index(IFI) with Addition of glomerular and tubular macrophages which were evaluated qualitatively through the macrophage marker (CD68) . The objective of this study was to assess reliability of the serum levels of VEGF and Bcl-2 in predicting disease activity and outcome in patients with lupus nephritis in addition to their clinicopathological correlation with different morphological variables from the new modified biopsy index. 40 patients with active lupus nephritis were included in this study. All patients were evaluated twice, once at time of presentation and again after 6 months from implementation of medical treatment. This evaluation included: serum samples to measure levels of VEGF and Bcl-2 by ELISA) and renal biopsy which was evaluated by: light microscopy, electron microscopy and immunohistochemistry using the new modified biopsy index in addition to staining of VEGF in collecting podocytes, distal convoluted tubules, collecting ducts by immunohistochemistry Glomerular and tubular macrophages were also stained by the macrophage marker (CD68) by immunohistochemistry.Serum VEGF levels showed a significant drop from a mean of (13.01ng/ml +/-6.45). At presentation with disease activity to a mean of (9.73 ng/ml+/-4.65)after 6 months (p 0.05). Statistical analysis data showed that serum VEGF correlated significantly with tubular cleen lle osis from ehl n modified biopsy indeX in a positive correlation throguhout the duration of this study(P<0.05). Also serum VEGF levels correlated in a postetie ncorrelation with the following morphological variables:cellular crescents, interstitial inflammation and NIH (AI) both at presentation and after 6 months. Within the same study, serum VEGF levels correlated negatively with serum C3 and C4 levels both at presentation and after 6 months but all of these correlations didn't reach statistical significance. VEGF in podocytes correlated with quantitative 24hs urinary proteins both at presentation and after 6 months in a significant positive correlation(P<0.05). Serum Bcl-2 levels correlate with karyorrhexis/fibrinoid necrosis in a positive but insignificant correlation at presentation which remained positive but turned out to be significant after 6 months(P<0.05) . Among the distinct morphological variables denoting disease activity in new modified biopsy index, both cellular crescents and interstitial inflammation correlated with serum Bcl-2 levels both at presentation and after 6 months in a positive but insignificant correlation. Both serum VEGF and Bcl-2 can be used reliably in patients with lupus nephritis for evaluation of disease activity, prognosis and the response to medical treatment at follow up especially in presence of a baseline serum level of VEGF or Bel-2 or both and a diagnostic renal biopsy, and if the need for a second look renal biopsy arises, it is advised to apply the new modified biopsy index in view of the dia gnostic and prognostic value of many of its components in an attempt to implement an appropriate line of treatment.

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年份:

2015

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