PDF(Pubmed)
Abstract：
Collagen VII is the main constituent of the anchoring fibrils, important adhesive structures that attach the epidermis to the dermal extracellular matrix. Two disorders are caused by dysfunction of collagen VII, both characterized by skin and mucosa fragility, epidermolysis bullosa acquisita (EBA) and dystrophic epidermolysis bullosa (DEB). EBA and DEB share high clinical similarities with significant difference in patients\' age of onset and pathogenesis. Our patients presented with severe and recalcitrant mechanobullous EBA with characteristic DIF, IIF and ELISA diagnostics. But in both women recessive COL7A1 variants were also found, in a monoallelic state. Collagen VII from EBA keratinocytes of our cases was significantly more vulnerable to proteolytic degradation than control keratinocytes, hinting that the heterozygous pathogenic variants were sufficient to destabilize the molecule in vitro. Thus, even if the amount and functionality of mutant and normal type VII collagen polypeptides is sufficient to assure dermal-epidermal adhesion in healthy individuals, the functionally-impaired proteins are probably more prone to development of autoantibodies against them. Our work suggests that testing for COL7A1 genetic variants should be considered in patients with EBA, which either have a patient history hinting towards underlying dystrophic epidermolysis bullosa or pose therapeutic challenges.
摘要：
胶原蛋白VII是锚定原纤维的主要成分，将表皮附着到真皮细胞外基质的重要粘附结构。两种疾病是由VII胶原蛋白的功能障碍引起的，都以皮肤和粘膜脆弱为特征，大疱性表皮松解症（EBA）和营养不良性大疱性表皮松解症（DEB）。EBA和DEB具有很高的临床相似性，在患者发病年龄和发病机制方面存在显着差异。我们的患者表现为具有特征性DIF的严重和顽固的机械球状EBA，IIF和ELISA诊断。但在这两名女性中，还发现了隐性COL7A1变异，处于单等位基因状态。我们病例的EBA角质形成细胞的VII型胶原比对照角质形成细胞更容易发生蛋白水解降解，暗示杂合致病变体足以在体外使分子不稳定。因此，即使突变和正常VII型胶原蛋白多肽的数量和功能足以确保健康个体的真皮-表皮粘附，功能受损的蛋白质可能更容易产生针对它们的自身抗体.我们的工作表明，在EBA患者中应该考虑检测COL7A1遗传变异，这些患者要么有病史暗示潜在的营养不良性大疱性表皮松解症，要么构成治疗挑战。
