Histological changes and immunohistochemical markers in the assessment of glomerulosclerosis in patients with glomerulonephritis

摘要

Introduction: Glomerular cells (mesangial, endothelial, epithelial) are activated during glomerulonephritis, a process indicated by the expression of the immunohistochemical marker alpha-smooth muscle actin (SMA). Many growth factors participate in the above-mentioned processes, among them of great importance is the transforming growth factor beta (TGF-beta). The result of these changes is represented by active lesions (mesangial matrix increase, mesangial cell proliferation) and chronic fibrotic lesions (glomerulosclerosis). Methodology: We studied a group of 41 patients with primary and secondary glomerulonephritis (24 males, 17 females, mean age 45.5+/-12.9 years), which underwent kidney biopsies, processed in light microscopy. We performed immunohistochemistry procedures with monoclonal antibodies (performed with the LSAB2-HRP system: anti-alpha-SMA, and anti-TGF-beta), which were assessed using a semiquantitative score, that was correlated with the histological and biological data. In order to quantify the histological changes and to assess the extent of active-inflammatory and chronic-sclerotic/fibrotic lesions, we adapted a scoring system initially used only for lupus nephritis, and ANCA-associated vasculitis. Results: TGF-beta expression in glomerular endothelial cells correlated with mesangial matrix increase (r=0.28, p<0.05), total activity index (r=0.29, p<0.05) and total chronicity index (r=0.34, p<0.05). Glomerular epithelial cell TGF-beta correlates with mesangial proliferation (r=0.29, p<0.05), mesangial matrix increase (r=0.4, p<0.01) and total activity index (r=0.28, p<0.05). We observed a strong correlation between endothelial immunolabeling of SMA and the mesangial proliferation score (r=-0.96, p<0.005) and also an indirect correlation with the glomerulosclerosis score (r=-0.35, p<0.05) and the total chronicity index (r=-0.39, p<0.05). Concerning biological data there was a correlation between mesangial SMA expression and serum creatinine (r=0.60, p<0.001) and an indirect correlation with GFR (r=-0.37, p<0.05). Conclusions: We conclude that TGF-beta has a key role in determining glomerulosclerosis especially through mesangial matrix increase, but possibly also through mesangial cells proliferation. Another role of this growth factor is related to transdifferentiation, not only epithelial-mesenchymal, but also endothelial-mesenchymal.