免疫组化检测Alport患者基底膜Ⅳ型胶原α链分布

IMMUNOHISTOCHEMICAL STUDY OF TYPE Ⅳ COLLAGEN CHAIN DISTRIBUTION WITHIN BASEMENT MEMBRANE IN PATIENTS WITH ALPORT SYNDROME

为了观察Ⅳ型胶原各链在Ａｌｐｏｒｔ综合征（ＡＳ）患者基底膜上分布，初步探讨ＡＳ的发病机制，评估间接免疫荧光法检测Ⅳ型胶原对ＡＳ的诊断价值，采用针对Ⅳ型胶原α１、３、４、５链ＮＣ１片段的特异性单克隆抗体，利用间接免疫荧光技术对Ⅳ型胶原在８例Ａｌｐｏｒｔ患者的肾（６例）及皮肤（５例）基底膜上的分布进行了检测。结果显示：４例Ｘ伴性显性（ＸＤ）遗传男性Ａｌｐｏｒｔ患者肾小球基底膜上有α３、４、５（Ⅳ）链共同缺失，表皮基底膜上α５（Ⅳ）链间接免疫荧光亦为阴性，而３例常染色体显性及１例常染色体隐性遗传的Ａｌｐｏｒｔ患者间接免疫荧光均为阳性，与正常结果相同。提示ＡＳ存在Ⅳ型胶原生化组成异常，ＸＤ－ＡＳ的发病与Ⅳ型胶原α５链的生成异常有关；皮肤及肾组织Ⅳ型胶原α链间接免疫荧光检测对ＸＤ－ＡＳ具重要诊断意义。

To observe the distribution of type Ⅳ collagen chains within basement membrane in patients with Alport syndrome (AS), discuss the pathogenesis of AS and assess the diagnostic value of indirect immunoflurescent study of type Ⅳ collagen chains. By using indirect immunofluorescence technique, the distribution of different chains of type Ⅳ collagen in speciment of renal (6 specimens) and skin (5 specimens) basement membrane of 8 AS patients belonging to 7 kindreds were investigated. In 4 male patients with Xlinked dominant (XD) AS, the specific monoclonal antibodies against NC1 domains of the α 3, α4 and α 5 chains of type Ⅳ collagen failed to localize on glomerular basement membrane (GBM) and the α 5 chain of type Ⅳ collagen were also absent in the epidermal basement membrane (EBM). The results of immunofluorescent study were positive in 3 autosomal dominant and 1 autosomal recessive AS patients as same as that in control. AS presents a biochemical abnormality of type Ⅳ collagen. The pathogenesis of XDAS may associate with the abnormal products of α 5 chain. The immunofluorescent study of type Ⅳ collagen chains distribution within GBM and EBM by using monoclonal antibodies is useful in confirming the diagnosis of AS, especially XDAS.