インテグリンα3免疫染色を用いた壁側上皮細胞の状態変化評価による潜在的なFSGSの同定
Hui You1, Kuo Wang2, Mingshu Zhang3
1Department of Nephrology, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatric Metabolism and Inflammatory Diseases, Chongqing, 400014, China; Key Laboratory of Biomacromolecules (CAS), CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
Abstract:
Diagnosing primary focal segmental glomerulosclerosis (FSGS) remains challenging due to the lack of reliable biomarkers. This study investigates Integrin α3 as a diagnostic biomarker to differentiate FSGS from minimal change disease (MCD) and to predict progression risk in patient with MCD. Renal biopsies were obtained from 64 patients with idiopathic nephrotic syndrome (INS) and analyzed, comprising 36 patients with MCD and 28 patients with FSGS. Integrin α3 expression and distribution were assessed via immunohistochemistry using a novel semi-quantitative scoring system (Int score: 0-3). Clinical correlations were analyzed using Pearson's correlation. Receiver operating characteristic (ROC) curve analysis evaluated the diagnostic utility of the Int score and established a cutoff to stratify MCD patients at risk for FSGS progression. We found that Integrin α3 was markedly upregulated in perilesional areas of FSGS glomeruli, colocalizing with Annexin A3, Claudin-1, and CD44. Focal Integrin α3 overexpression was observed in 73.08% of FSGS cases versus 19.44% of MCD. In MCD, 60.62% of glomeruli scored Int 0, whereas 74.36% of FSGS scored ≥1. ROC curve analysis revealed the strong discrimination ability of the Int score (AUC = 0.91). The Int score correlated positively with podocyte damage, 24-hour proteinuria and the proportion of glomeruli with segmental sclerosis, and inversely with serum albumin and estimated glomerular filtration rate (eGFR). Based on the Int score, seven patients with MCD were stratified into the high-FSGS-probability group. These patients exhibited broader foot process widths and longer durations of proteinuria compared to other MCD patients. Overall, parietal epithelial cells (PECs) with Integrin α3 overexpression invading the glomerular tuft contribute to the sclerotic lesion. Integrin α3 expression patterns may serve as a histopathological biomarker to distinguish FSGS from MCD and identifying patients initially misdiagnosed as MCD and enabling early intervention and tailored monitoring.
