Barsotti P, Muda A O, Mazzucco G, Massella L, Basolo B, De Marchi M, Rizzoni G, Monga G, Faraggiana T
Dipartimento di Medicina Sperimentale e Patologia, Università La Sapienza, Viale Regina Elena, 324 (Policlinico Umberto I), I-00161 Rome, Italy.
Nephrol Dial Transplant. 2001 May;16(5):945-52. doi: 10.1093/ndt/16.5.945.
In Alport syndrome (AS) impaired production and/or assembly of col IV alpha-chain isoforms results in abnormal structure of glomerular basement membrane (GBM), haematuria and, frequently, progressive renal disease. We investigated the relationship between col IV alpha-chains expression and morphology of GBM, as a possible key to the better understanding of the pathogenesis of renal disease in AS.
GBM distribution of col IV alpha1-, alpha3-, and alpha5-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).
Col IV alpha1-chain was demonstrated in GBM of all patients. Three patterns of staining for col IValpha3- and alpha5-chains were observed: positive, negative, and alpha3(IV)-positive/alpha5(IV)-negative. By chi(2)-test, EM class III lesions and complete loss of alpha3(IV)- and alpha5(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 alpha5(IV)-chain. Intensity of alpha3(IV)-chain staining, however, had a negative correlation (P<0.05) with the severity of GBM basket weaving.
Our results suggest that the alpha3(IV)-chain-containing col IV-network plays a fundamental role in structural and, possibly, functional organization of GBM. Absence of alpha3(IV)-chain in GBM could indicate a more severe renal disease in AS.
在奥尔波特综合征（AS）中，IV型胶原α链异构体的产生和/或组装受损导致肾小球基底膜（GBM）结构异常、血尿，且常伴有进行性肾病。我们研究了IV型胶原α链表达与GBM形态之间的关系，这可能是更好理解AS肾病发病机制的关键。
对32例（21例男性和11例女性，活检时平均年龄11.5岁）超微结构表现提示AS的患者，采用免疫组织化学法研究IV型胶原α1、α3和α5链在GBM中的分布。10例患者证实存在COL4A5突变。根据超微结构表现的严重程度，将活检标本分为三个（I - III）电子显微镜（EM）级别。使用半定量量表（0 - 3）对GBM的显著EM变化（变薄、增厚、分裂、致密层篮状编织）进行单独评估。
所有患者的GBM中均检测到IV型胶原α1链。观察到IV型胶原α3和α５链的三种染色模式：阳性、阴性以及α3（IV）阳性/α5（IV）阴性。通过卡方检验，男性患者中EM III级病变以及α3（IV）和α5（IV）抗原完全缺失的情况显著更常见（P < 0.05和P < 0.01），但EM级别与免疫组化模式之间未观察到显著相关性。GBM改变与α5（IV）链染色无关。然而，α3（IV）链染色强度与GBM篮状编织的严重程度呈负相关（P < 0.05）。
我们的结果表明，含有α3（IV）链的IV型胶原网络在GBM的结构以及可能的功能组织中起重要作用。GBM中缺乏α3（IV）链可能表明AS患者的肾病更为严重。
