C5b-9 glomerular deposition and tubular α3β1-integrin expression are implicated in the development of chronic lesions and predict renal function outcome in immunoglobulin A nephropathy
C5b-9 glomerular deposition and tubular α3β1-integrin expression are implicated in the development of chronic lesions and predict renal function outcome in immunoglobulin A nephropathy
复制标题
DOI：
10.1080/00365590801943241
复制
发表时间：
2008-01-01
影响因子：
--
通讯作者：
Memmos, Dimitrios
中科院分区：
文献类型：
--
作者：
Stangou, Maria;Alexopoulos, Efstathios;Memmos, Dimitrios
Objective.肾小管萎缩是预测原发性免疫球蛋白A肾病（IgAN）肾功能预后不良的因素之一。然而，肾小管萎缩的发展是疾病进展期间的晚期现象。这将有助于识别可能导致肾损害的早期因素，并可用作肾脏结局的早期预测因子。材料和方法。对48例IgA肾病患者进行回顾性检查。所有患者在研究开始时均进行了肾活检。对组织学参数进行了审查，并对冷冻切片进行了免疫组织化学。使用的单克隆抗体针对C5 b-9、α（3）β（1）-整联蛋白、转化生长因子-β（1）（TGF-beta（1））和α-平滑肌肌动蛋白（alpha-SMA），结果与组织学数据和长期相关肾功能结果。结果在肾小球中，C5 b-9沉积的程度与局灶性肾小球硬化的程度（p=0.005）、肾小管萎缩（p=0.003）、间质炎症（p=0.005）和α（3）β（1）肾小管表达（p=0.0001）显著正相关。肾小管α 3 β 1表达与蛋白尿的严重程度（p=0.01）、肾小球和肾小管间质肌成纤维细胞的数量、肾小管萎缩的程度（p=0.0001）和间质单核细胞浸润（p=0.005）呈正相关。肾小管α（3）β（1）表达和肾小管萎缩程度分别在随访开始和结束时对肾功能衰竭的发展有重要意义。结论. C5 b-9在肾小球的沉积可能参与了IgAN肾小球硬化的发生发展。此外，它与肾小管α（3）β（1）-整合素的强度呈正相关，提示可能与肾小管间质纤维化的发生有关。
Objective. Tubular atrophy is one of the factors predicting poor outcome of renal function in primary immunoglobulin A nephropathy (IgAN). However, the development of tubular atrophy is a late phenomenon during the disease progression. It would be useful to identify early factors that potentially result in renal damage and could be used as early predictors of renal outcome. Material and methods. Forty-eight patients with IgAN were examined retrospectively. All patients had a renal biopsy at the beginning of the study. Histological parameters were reviewed and immunohistochemistry was performed on cryostat sections. Monoclonal antibodies used were against C5b-9, alpha(3)beta(1)-integrin, transforming growth factor-beta(1) (TGF-beta(1)) and alpha-smooth muscle actin (alpha-SMA), and the results were correlated with histological data and long-term outcome of renal function. Results. In the glomeruli the extent of C5b-9 deposition had significant positive correlations with the degree of focal glomerulosclerosis (p=0.005), tubular atrophy (p=0.003), interstitial inflammation (p=0.005) and tubular expression of alpha(3)beta(1) (p=0.0001). alpha(3)beta(1) tubular expression correlated positively with the severity of proteinuria (p=0.01), number of glomerular and tubulointerstitial myofibroblasts, and the degree of tubular atrophy (p=0.0001) and interstitial monocyte infiltration (p=0.005). Tubular alpha(3)beta(1) expression and the degree of tubular atrophy had significant implications in the development of renal failure at the beginning and at the end of follow-up, respectively. Conclusions. Glomerular deposition of C5b-9 may participate in the development of glomerulosclerosis in IgAN. Furthermore, its positive correlation with the intensity of tubular alpha(3)beta(1)-integrin suggests a possible implication in the development of tubulointerstitial fibrosis.