Nephritogenic antigen determinants in epidermal and renal basement membranes of kindreds with Alport-type familial nephritis.
Nephritogenic antigen determinants in epidermal and renal basement membranes of kindreds with Alport-type familial nephritis.
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Alport 型家族性肾炎家族表皮和肾基底膜中的肾炎抗原决定簇。
DOI：
10.1172/jci112658
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发表时间：
1986
期刊：
影响因子：
--
通讯作者：
Michael,AF
中科院分区：
文献类型：
--
作者：
Kashtan,C;Fish,AJ;Kleppel,M;Yoshioka,K;Michael,AF
我们对患有 Alport 型家族性肾炎 (FN) 家族成员的酸尿素变性皮肤的表皮基底膜 (EBM) 进行了检测，以确定是否存在与来自一位 Alport 患者的 Goodpasture 血清 (GPS) 和血清 (FNS) 反应的抗原，该患者在同种异体移植肾中出现了抗肾小球基底膜 (GBM) 肾炎。通过免疫印迹，GPS 主要与来自正常人 GBM 的 IV 型胶原的非胶原球状结构域 (NC1) 的 28,000 分子量 (mol wt) 单体发生反应，但也与 24,000 mol wt 和 26,000 mol wt 单体发生反应，而 FNS 仅识别出 26,000 mol wt 单体。 FNS 对 12 名对照者和 9 名未受影响的男性亲属成员的 EBM 产生反应，但对 8 名受影响男性的 EBM 没有反应。五名受影响的女性表现出 FNS 与 EBM 的反应性中断。 GPS 显示与 EBM 的不同反应性，并且对于 Alport 型 FN 没有区别。 FNS 没有对五名受影响男性的肾基底成员进行染色。然而，受影响男性的 EBM、管状基底膜和鲍曼氏囊含有与 GPS 反应的抗原。这些免疫化学研究表明 FNS 抗原与 Goodpasture 抗原不同。位于 IV 型胶原 NC1 结构域上的 FNS 抗原的表达在 Alport 型 FN 患者的基底膜中发生改变，这种抗原异常在亲属中的分布表明缺陷基因的 X 连锁显性遗传。
We probed epidermal basement membranes (EBM) of acid-urea denatured skin from members of kindreds with Alport-type familial nephritis (FN) for the presence of antigens reactive with Goodpasture sera (GPS) and serum (FNS) from an Alport patient who developed anti-glomerular basement membrane (GBM) nephritis in a renal allograft. By immunoblotting, GPS reacted primarily with the 28,000 molecular weight (mol wt) monomer but also the 24,000 mol wt and 26,000 mol wt monomers of the noncollagenous globular domain (NC1) of type IV collagen from normal human GBM, while FNS identified only the 26,000-mol wt monomer. FNS reacted with EBM of 12 controls and nine unaffected male kindred members but not EBM of eight affected males. Five affected females exhibited interrupted reactivity of FNS with EBM. GPS showed variable reactivity with EBM and was not discriminating with respect to Alport-type FN. FNS did not stain renal basement members of five affected males. However, the EBM, tubular basement membrane, and Bowman's capsules of affected males contained antigens reactive with GPS. These immunochemical studies suggest that the FNS antigen is distinct from Goodpasture antigen(s). The expression of FNS antigen located on the NC1 domain of type IV collagen is altered in basement membranes of patients with Alport-type FN, and the distribution of this antigenic anomaly within kindreds suggests X-linked dominant transmission of a defective gene.Images