Mapping the binding sites of anti-BP180 immunoglobulin E autoantibodies in bullous pemphigoid
Mapping the binding sites of anti-BP180 immunoglobulin E autoantibodies in bullous pemphigoid
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DOI：
10.1111/j.0022-202x.2005.23853.x
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发表时间：
2005-09-01
影响因子：
6.5
通讯作者：
Giudice, GJ
中科院分区：
文献类型：
--
作者：
Fairley, JA;Fu, CL;Giudice, GJ
大疱性类天疱疮（BP）是一种表皮下水疱性疾病，其特征是抗半桥粒蛋白BP 180（BPAg 2，XVII型胶原）的自身抗体。NC 16 A是BP 180胞外域的非胶原延伸，是致病性免疫球蛋白（IG）G自身抗体和IgE类自身抗体的主要靶标。本研究进一步表征了BP 180的IgE反应性区域。在来自未治疗的BP患者的10份血清中，8份含有与整个BP 180胞外域反应的IgE。这8份血清中有4份的IgE与NC 16 A反应，而在其余4份血清中，IgE免疫反应性仅限于NC 16 A下游的位点。相比之下，在10份BP血清中的9份中检测到IgG对NC 16 A的反应性，并且在剩余的血清中，IgG以及IgE仅与BP 180胞外域上的非NC 16 A位点反应。NC 16 A内的抗原位点的精细作图揭示了IgE和IgG的非常相似的反应模式，NC 16 A亚区-2是由两种同种型识别的主要位点。八个未经治疗的BP患者进行了测试，组胺释放从他们的嗜碱性粒细胞响应NC 16 A。抗原特异性组胺释放仅在那些具有针对NC 16 A的可检测循环IgE的患者中观察到（8例中的3例）。未来的研究将调查抗BP 180 IgE的致病相关性。
Bullous pemphigoid (BP) is a subepidermal blistering disease characterized by autoantibodies against the hemidesmosomal protein BP180 (BPAg2, type XVII collagen). NC16A, a non-collagenous stretch of the BP180 ectodomain, is the primary target of pathogenic immunoglobulin (Ig)G autoantibodies and IgE class autoantibodies. This study further characterized the IgE-reactive regions of BP180. Of the ten sera from untreated BP patients, eight contained IgE reactive with the entire BP180 ectodomain. The IgE in four of these eight sera reacted with NC16A, whereas in the remaining four sera IgE immunoreactivity was restricted to sites downstream of NC16A. In contrast, IgG reactivity to NC16A was detected in nine of the ten BP sera, and in the remaining serum, IgG, as well as IgE, reacted exclusively with non-NC16A sites on the BP180 ectodomain. Fine mapping of the antigenic sites within NC16A revealed very similar reactivity patterns for IgE and IgG, with NC16A subregion-2 being the major site recognized by both isotypes. Eight of the untreated BP patients were tested for histamine release from their basophils in response to NC16A. Antigen-specific histamine release was observed only in those patients with detectable circulating IgE directed against NC16A (three of eight). Future studies will investigate the pathogenic relevance of anti-BP180 IgE.