Correlation between ultrastructural changes of glomerular basement membrane and abnormal distribution of laminins in patients with Alport' s syndrome / 北京大学学报(医学版)

ABSTRACT

Objective:To analyse the relationship of ultrastructural changes of glomerular basement membrane (GBM) and glomerular distributions of laminin α1 and laminin α5 in patients with Alport' s syndrome. Methods: Twenty patients with Alport' s syndrome were recruited. The thickness of GBM and the extension of thickening and splitting GBM were measured under transmission electron microscope. Normal renal tissues from 6 nephrectomies of renal carcinoma were taken as controls. Paraffin embedded sections of formalin-fixed renal tissue were processed for immunohistochemistry with monoclonal antibodies to laminin α1 and laminin α5. Their distributions in GBM were evaluated by a semiquantitative scale of positive extension; absent, 0≤25% , 1; 25%-50% , 2; 50%-75% , 3;≥75% , 4. Results: There were a variety of degrees of thickening or splitting GBM in patients with Alport' s syndrome. Laminin al was positive in glomerular mesangial area and absolutely negative in GBM and laminin α5 was evenly positive in GBM in normal tissue. In Alport' s syndrome, laminin α1 was much weaker in glomerular mesangial area, but strongly positive in GBM; laminin α5 in GBM was prominently reduced. There was a high negative correlation of semiquantitative scores between laminin al and laminin α5 (r =-0. 83, P＜0. 001). The extension of thickening or splitting GBM was positively correlated with scores of laminin al in GBM ( r = 0. 76, P＜0.001; r = 0. 56, P=0. 015 ) , and was negatively correlated with scores of laminin α5 in GBM ( r =-0. 59, P =0. 010; r=-0. 53, P =0.025). Conclusion: Abnormal distribution of laminin al and laminin α5 in GBM is correlated with GBM thickening and splitting in human Alport' s syndrome.