Immunoadsorption against two distinct epitopes on human type XVII collagen abolishes dermal-epidermal separation induced in vitro by autoantibodies from pemphigoid gestationis patients
Immunoadsorption against two distinct epitopes on human type XVII collagen abolishes dermal-epidermal separation induced in vitro by autoantibodies from pemphigoid gestationis patients
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DOI：
10.1002/eji.200535349
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发表时间：
2006-04-01
影响因子：
5.4
通讯作者：
Sitaru, C
中科院分区：
文献类型：
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作者：
Herrero-González, JE;Brauns, O;Sitaru, C
妊娠类天疱疮 (PG) 是一种表皮下自身免疫性水疱性疾病，其特征是对 XVII 型胶原蛋白/BP180 跨膜半桥粒蛋白具有特异性的自身反应性 T 细胞和 B 细胞。主要 T 和 B 细胞表位位于 XVII 型胶原的免疫显性第 16（th）非胶原结构域 A (NC16A) 内。本研究的目的是绘制水疱诱导患者自身抗体针对的致病相关表位图谱。为此，我们使用了自身抗体诱导的白细胞依赖性真皮-表皮分离的体外模型。针对 NC16A 区域重组形式的预吸附消除了所有 PG 患者自身抗体诱发水疱的潜力。使用重叠的合成肽，我们证明 PG 自身抗体与 NC16A 区域内的两个确定的表位（aa 500-514 和 aa 511-523）结合。重要的是，使用含有这些表位的亲和基质进行预吸附完全消除了 PG 自身抗体诱导的真皮-表皮分离。这项研究确定了与 PG 中水疱诱导相关的表位，并应有助于开发针对该疾病的抗原特异性免疫吸附疗法。
Pemphigoid gestationis (PG) is a subepidermal autoimmune blistering disease characterized by self-reactive T and B cells specific for the transmembrane hemidesmosomal protein type XVII collagen/BP180. Major T and B cell epitopes are located within the immunodominant 16(th) non-collagenous domain A (NC16A) of type XVII collagen. The aim of the present study was to map the pathogenically relevant epitopes targeted by blister-inducing patients'autoantibodies. For this purpose, we used an in vitro model of autoantibody-induced leukocyte-dependent dermal-epidermal separation. Pre-adsorption against a recombinant form of the NC16A region abolished the blister-inducing potential of autoantibodies from all PG patients. Using overlapping synthetic peptides, we demonstrated that PG autoantibodies bind to two defined epitopes within the NC16A region (aa 500-514 and aa 511-523). Importantly, pre-adsorption using an affinity matrix containing these epitopes completely abolished dermal-epidermal separation induced by PG autoantibodies. This study identifies the epitopes relevant for blister induction in PG and should facilitate the development of an antigen-specific immunoadsorption therapy for this disease.