Nephrol Dial Transplant (2001) 16: 945-952
© 2001 European Renal Association-European Dialysis and Transplant Association
Distribution of 
-chains of type IV collagen in glomerular basement membranes with ultrastructural alterations suggestive of Alport syndrome
1 Dipartimento di Medicina Sperimentale e Patologia, Università ‘La Sapienza’, Roma 2 Dipartimento di Scienze Biomediche ed Oncologia, Università di Torino, Torino 3 Divisione di Nefrologia, Ospedale Pediatrico Bambino Gesù, IRCCS, Roma 4 Divisione di Nefrologia e Dialisi, Ospedale San Giovanni Bosco, Torino 5 Dipartimento di Scienze Cliniche e Biologiche, Università di Torino, Orbassano 6 Dipartimento di Scienze Mediche, Università di Torino, Novara, Italy
Background. In Alport syndrome (AS) impaired production and/or assembly of col IV 
-chain isoforms results in abnormal structure of glomerular basement membrane (GBM), haematuria and, frequently, progressive renal disease. We investigated the relationship between col IV -chains expression and morphology of GBM, as a possible key to the better understanding of the pathogenesis of renal disease in AS.
Methods. GBM distribution of col IV 1-, 3-, and 5-chain was investigated by immunohistochemistry in 32 patients (21 males and 11 females, mean age at biopsy of 11.5 years) with ultrastructural findings suggestive of AS. Ten patients had a proven COL4A5 mutation. Based on the severity of ultrastructural findings, the biopsies were grouped in three (I–III) electron microscopy (EM) classes. Significant EM changes of GBM (thinning, thickening, splitting, basket weaving of the lamina densa) were singularly evaluated using a semiquantitative scale (0–3).
Results. Col IV 1-chain was demonstrated in GBM of all patients. Three patterns of staining for col IV3- and 5-chains were observed: positive, negative, and 3(IV)-positive/5(IV)-negative. By 
2-test, EM class III lesions and complete loss of 3(IV)- and 5(IV)-antigen were significantly more frequent (P<0.05 and P<0.01) in male patients, but no significant relation was observed between EM classes and immunohistochemical patterns. GBM alterations did not correlate with staining for 5(IV)-chain. Intensity of 3(IV)-chain staining, however, had a negative correlation (P<0.05) with the severity of GBM basket weaving.
Conclusions. Our results suggest that the 3(IV)-chain-containing col IV-network plays a fundamental role in structural and, possibly, functional organization of GBM. Absence of 3(IV)-chain in GBM could indicate a more severe renal disease in AS.
Keywords: Alport syndrome; COL4A5 gene mutations; electron microscopy; glomerular basement membrane; immunohistochemistry; type IV collagen
Correspondence and offprint requests to: Dr Paola Barsotti, Università ‘La Sapienza’, Dipartimento di Medicina Sperimentale e Patologia, Sezione di Patologia Ultrastrutturale, Viale Regina Elena, 324 (Policlinico Umberto I), I-00161 Roma, Italy.
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