Alport综合征患者肾组织层粘连蛋白α2链异常分布

目的 观察Alport综合征(AS)患者肾组织层粘连蛋白α2链、α5链和γ1链的分布。方法 采用免疫荧光方法,运用普通荧光和激光共聚焦扫描显微镜观察抗层粘连蛋白α2链、α5链和γ1链单克隆抗体在肾组织中的沉积情况。肾组织标本来自11例AS患者,其中男8例,女3例,年龄11~52岁。10例患者符合X伴性显性遗传(XLAS),1例女性患者符合显性遗传。8例男性XLAS患者肾小球基底膜(GBM)、远端肾小管基底膜均无Ⅳ型胶原α3、5链沉积,表皮基底膜(EBM)无α5(Ⅳ)链沉积;2例女性XLAS患者肾组织α3、5(Ⅳ)链和EBM α5(Ⅳ)链均呈不连续表达,另1例女性患者则同正常肾组织。正常人肾组织标本作为正常对照,9例IgA肾病(IgAN)、6例局灶节段硬化性肾小球病(FSGS)、5例薄基膜病(TBMD)和6例肾小球轻微病变(GML)患者作为疾病对照。结果 正常人肾组织层粘连蛋白α2链主要沉积于肾小球系膜区,层连蛋白α5、γ1链沉积于GBM、所有肾小管基底膜和入球小动脉基底膜。10例XLAS和1例显性遗传AS患者肾组织除了肾小球系膜区外,层粘连蛋白α2链在GBM上亦出现表达。IgAN、TBMD和FSGS患者层粘连蛋白α2链仅在肾小球系膜区沉积。层粘连蛋白α5、γ1链在AS患者和其他肾脏病组织沉积同正常肾组织。结论 层粘连蛋白α2链在AS患者GBM出现异位表达,为继Ⅳ型胶原α链异常之后发现的又一AS基底膜成分的异常,其对于AS可能具有重要的诊断价值。

Abnormal distribution of laminin α2 chain in renal tissues of patients with Alport syndrome

Objective To identify the distribution of the laminin α5, α2 andγ1 chains within renal basement membrane in Alport syndrome (AS). Methods Kidney tissues from 11 patients of AS, 9 IgA nephropathy (IgAN), 6 focal segmental glomerular sclerosis (FSGS), 5 thin basement membrane disease (TBMD), 6 minor change glomerulonephritis and 3 normal people were examined by immunofluorescence and confocal microscopy for the expression of laminin α5, α2 andγ1 chains. Among 11 Alport patients, 8 male and 2 female patients inherited as X-linked dominant trait and 1 female inherited as dominant trait. The expression of theα3,5 chains of type Ⅳ collagen in GBM were co-absent in all 8 male Alport patients and were partially absent in 2 female patients, whereas their expression were normal in another female patient. Results Laminin α2 chain was deposited in the mesangium and absent from GBM in normal people, but was abnormally deposited in Alport GBM. GBM lamininα2 chain deposition was not observed in IgAN, FSGS, TBMD and minor change glomerulonephritis. As in normal kidney, Alport kidney revealed similar staining for the lamininα5 and γ1 chains. Conclusions Laminin is one of the main components in GBM and mesangium. Abnormal deposition of lamininα2 chain is of clinical importance in AS diagnosis.