Autoantibodies to type VII collagen recognize epitopes in a fibronectin-like region of the noncollagenous (NC1) domain.
Autoantibodies to type VII collagen recognize epitopes in a fibronectin-like region of the noncollagenous (NC1) domain.
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VII 型胶原蛋白自身抗体可识别非胶原 (NC1) 结构域的纤连蛋白样区域中的表位。
DOI：
10.1111/1523-1747.ep12472291
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发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Hunt3rd,SW
中科院分区：
文献类型：
--
作者：
Gammon,WR;Murrell,DF;Jenison,MW;Padilla,KM;Prisayanh,PS;Jones,DA;Briggaman,RA;Hunt3rd,SW
VII型胶原自身抗体是获得性大疱性表皮病和大疱性系统性红斑狼疮（SLE）的特征。这些疾病中的水疱是由于上皮基底膜的致密层亚区与下层真皮的粘附缺陷所致。先前的研究表明，VII型胶原蛋白通过交联致密层和真皮基质蛋白而促进致密层-真皮粘附，这表明自身抗体可能通过干扰VII型胶原蛋白功能而促进水疱。这一假设得到了先前研究的支持，这些研究表明，来自少数获得性大疱性表皮病患者的自身抗体识别含有VII型胶原的145 kD非胶原结构域的蛋白水解片段。在这项研究中，我们研究了大量的获得性大疱性表皮病和大疱性SLE患者的自身抗体与融合蛋白的反应性，这些融合蛋白代表了VII型胶原蛋白的大部分非胶原结构域，并且这些区域与纤连蛋白的III型重复序列同源。这些结果表明，自身抗体结合到纤连蛋白的同源区域内的145 kD的非胶原结构域可能会干扰VII型胶原的粘附功能，并有助于在表皮大疱性获得性和大疱性系统性红斑狼疮致密层真皮粘附不良。
Autoantibodies to type VII collagen are characteristic of the blistering diseases epidermolysis bullosa acquisita and bullous systemic lupus erythematosus (SLE). Blisters in those diseases are due to defective adhesion of the lamina densa subregion of the epithelial basement membrane to the underlying dermis. Previous studies indicating that type VII collagen contributes to lamina densa-dermal adhesion by cross-linking lamina densa and dermal matrix proteins suggests that autoantibodies may contribute to blisters by interfering with type VII collagen function. That hypothesis is supported by previous studies showing autoantibodies from a small number of epidermolysis bullosa acquisita patients recognize proteolytic fragments containing the 145- kD noncollagenous domain of type VII collagen. In this study, we examined reactivity of autoantibodies from a large number of epidermolysis bullosa acquisita and bullous SLE patients with fusion proteins representing most of the noncollagenous domain of type VII collagen and that those regions are homologous to type III repeats of fibronectin. These results suggest autoantibodies binding to fibronectin homology regions within the 145-kD noncollagenous domain may interfere with the adhesion function of type VII collagen and contribute to lamina densa-dermal dysadhesion in epidermolysis bullous acquisita and bullous SLE.