The 97 kDa linear IgA bullous dermatosis antigen is not expressed in a patient with generalized atrophic benign epidermolysis bullosa with a novel homozygous G258X mutation in COL17A1.
The 97 kDa linear IgA bullous dermatosis antigen is not expressed in a patient with generalized atrophic benign epidermolysis bullosa with a novel homozygous G258X mutation in COL17A1.
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具有 COL17A1 新型纯合 G258X 突变的全身性萎缩性良性大疱性表皮松解症患者中不表达 97 kDa 线性 IgA 大疱性皮肤病抗原。
DOI：
10.1046/j.1523-1747.1998.00363.x
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Nishikawa,T
中科院分区：
文献类型：
--
作者：
Shimizu,H;Takizawa,Y;Pulkkinen,L;Zone,JJ;Matsumoto,K;Saida,T;Uitto,J;Nishikawa,T
97 kDa线性伊加大疱性皮肤病抗原（LAD-1）的性质和表达模式及其在大疱性表皮病中的作用尚未完全阐明。在这项研究中，我们研究了70例不同亚型的大疱性表皮病患者的皮肤标本中LAD-1的表达，包括单纯型（n = 23），交界型（n = 15）和营养不良型（n = 32）。对于免疫标记，我们使用了两个最近开发的单克隆抗体LAD-1的表位超微结构定位于之间的NC 16 A和羧基末端结构域的BPAG 2，以及对LAD-1的两个线性伊加皮肤病患者的血清中的自身抗体的透明板。在70例患者中，只有1例全身性萎缩性良性大疱性表皮病患者未显示LAD-1表达。虽然其他主要的基底膜成分，包括层粘连蛋白5，BPAG 1，plectin，α6和β4整联蛋白，以及IV型和VII型胶原蛋白正常表达，但BPAG 2/XVII型胶原蛋白在该患者的皮肤中不存在。采用聚合酶链反应扩增、异源双链扫描和直接核苷酸测序对COL 17 A1进行突变分析，结果显示该患者为外显子11中一种新的无义突变G258 X纯合子，其父母为该突变的杂合子携带者。这是位于BPAG 2胞内结构域的第一个突变，位于LAD-1 N-末端氨基酸序列上游817 bp处。这些发现表明，LAD-1的表达缺失是在BPAG 2缺陷的泛发性萎缩性良性大疱性表皮病患者中观察到的，该患者在COL 17 A1的两个等位基因中都有突变，而在其他大疱性表皮病亚型中则没有。这些发现也支持LAD-1是BPAG 2的降解产物的观点。
The nature and expression pattern of the 97 kDa linear IgA bullous dermatosis antigen (LAD-1) and its role in epidermolysis bullosa have not been fully elucidated. In this study, we examined the expression of LAD-1 in the skin specimens of 70 patients with the various subtypes of epidermolysis bullosa, including simplex (n = 23), junctional (n = 15), and dystrophic variants (n = 32). For immunolabeling, we used two recently developed monoclonal antibodies to LAD-1 whose epitopes were ultrastructurally localized in the lamina lucida between NC16A and carboxyterminal domains of BPAG2, as well as autoantibodies against LAD-1 from the sera of two patients with linear IgA dermatosis. Among the 70 patients, only one patient with generalized atrophic benign epidermolysis bullosa failed to demonstrate LAD-1 expression. Although other major basement membrane components, including laminin 5, BPAG1, plectin, α6 and β4 integrins, as well as type IV and type VII collagens were normally expressed, BPAG2/type XVII collagen was absent from the skin of this patient. Mutation analysis on COL17A1 using polymerase chain reaction amplification, heteroduplex scanning, and direct nucleotide sequencing revealed that this patient was homozygous for a novel nonsense mutation G258X in exon 11, and her parents were heterozygous carriers for this mutation. This is the first mutation located in the intracellular domain of BPAG2, and resides 817 bp upstream from the N-terminal amino acid sequence of LAD-1. These findings indicate that the absent expression of LAD-1 is observed in a BPAG2-deficient generalized atrophic benign epidermolysis bullosa patient with mutations in both alleles of COL17A1, and not in other epidermolysis bullosa subtypes. These findings also support the notion that LAD-1 is a degradation product of BPAG2.
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