[Correlation between ultrastructural changes of glomerular basement membrane and abnormal distribution of laminins in patients with Alport's syndrome].
OBJECTIVE
To analyse the relationship of ultrastructural changes of glomerular basement membrane (GBM) and glomerular distributions of laminin alpha1 and laminin alpha5 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 alpha1 and laminin alpha5. Their distributions in GBM were evaluated by a semiquantitative scale of positive extension: absent, 0; < or =25%, 1; 25%-50%, 2; 50%-75%, 3; > or =75%, 4.


RESULTS
There were a variety of degrees of thickening or splitting GBM in patients with Alport's syndrome. Laminin alpha1 was positive in glomerular mesangial area and absolutely negative in GBM and laminin alpha5 was evenly positive in GBM in normal tissue. In Alport's syndrome, laminin alpha1 was much weaker in glomerular mesangial area, but strongly positive in GBM; laminin alpha5 in GBM was prominently reduced. There was a high negative correlation of semiquantitative scores between laminin alpha1 and laminin alpha5 (r=-0.83, P<0.001). The extension of thickening or splitting GBM was positively correlated with scores of laminin alpha1 in GBM (r=0.76, P<0.001; r=0.56, P=0.015), and was negatively correlated with scores of laminin alpha5 in GBM (r=-0.59, P=0.010; r=-0.53, P=0.025).


CONCLUSIONS
Abnormal distribution of laminin alpha1 and laminin alpha5 in GBM is correlated with GBM thickening and splitting in human Alport's syndrome.
Huang
Wei
W
Department of Nephrology, Peking University Institute of Nephrology, Peking University First Hospital, Beijing 100034, China.
Wang
Chen
C
Zheng
Xin
X
Ao
Jie
J
Wang
Su-xia
SX
Liu
Gang
G
D000293:Adolescent; D000328:Adult; D002648:Child; D005260:Female; D050533:Glomerular Basement Membrane / Q000378:metabolism / Q000648:ultrastructure*; D005920:Glomerular Mesangium / Q000378:metabolism; D006801:Humans; D007797:Laminin / Q000378:metabolism*; D008297:Male; D009394:Nephritis, Hereditary / Q000378:metabolism* / Q000473:pathology*; D055815:Young Adult
D007797:Laminin; C097043:laminin alpha5; C084098:laminin A