Hereditary nephritis (Alport syndorome) : abnormalities in type IV collagen alpha5 chain and skin diagnosis

为了确定Alport综合征患者IV型胶原α5链α5(IV)的异常，我们使用识别α5(IV)非共识氨基酸序列的鼠单抗检测了肾脏和皮肤组织。正常人肾脏和皮肤组织的免疫荧光显示，α5(IV)在肾小球基底膜、鲍曼囊、部分肾小管和表皮BM中呈线形染色。来自4个X连锁Alport综合征家系的5名男性患者的肾脏标本在肾小球、鲍曼囊和肾小管中未见α5(IV)反应。在这些患者中，Alpha1(IV)和Alpha2(IV)正常，而Alpha3(IV)、Alpha4(IV)、Alpha5(IV)和Alpha6(IV)在肾脏BMS中缺失。男性患者皮肤组织中未检测到α5(IV)和α6(IV)。X-连锁Alport综合征女性杂合子的表皮BM表现为α5(IV)和α6(IV)的镶嵌染色。这些发现表明，X连锁Alport综合征患者除了α3(IV)-α4(IV)-α5(IV)网络紊乱外，还存在肾脏和表皮BMS蛋白水平的α6(IV)异常。

To identify the abnormalities of the type IV collagen alpha5 chain, alpha5 (IV), in Alport syndrome, we examined renal and skin tissues using rat monoclonal antibodies recognizing non-consensus amino acid sequences of alpha5 (IV). Immunofluorescence of normal human kidney and skin tissues revealed linear alpha5 (IV) staining in the basement membrane (BM) of glomerulus, Bowman's capsule, in some tubules and also in the epidermal BM.Renal specimens from 5 male patients of 4 families with X-linked Alport syndrome showed no reactivity for alpha5 (IV) in glomerulus, Bowman's capsules and tubules. In these patients, alpha1 (IV) and alpha2 (IV) were normal, whereas alpha3 (IV), alpha4 (IV), alpha5 (IV) and alpha6 (IV) were absent from the BMs of the kidney. In skin tissues of male patients, neither alpha5 (IV) nor alpha6 (IV) were detected. The epidermal BM of female heterozygotes with X-linked Alport syndrome showed a mosaic staining for alpha5 (IV) and alpha6 (IV). These findings indicate that, in addition to a disturbed alpha3 (IV) -alpha4 (IV) -alpha5 (IV) network, patients with X-linked Alport syndrome have abnormalities in alpha6 (IV) of the renal and epidermal BMs at the protein level.