Severity and phenotype of bullous pemphigoid relate to autoantibody profile against the NH2- and COOH-terminal regions of the BP180 ectodomain
Severity and phenotype of bullous pemphigoid relate to autoantibody profile against the NH2- and COOH-terminal regions of the BP180 ectodomain
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DOI：
10.1046/j.1523-1747.2002.19529.x
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发表时间：
2002-11-01
影响因子：
6.5
通讯作者：
Hertl, M
中科院分区：
文献类型：
--
作者：
Hofmann, S;Thomas-Uszynski, S;Hertl, M
大疱性类天疱疮是最常见的自身免疫性真皮下大疱性疾病，与针对聚集在BP180细胞外区域内的抗原位点的自身抗体有关。为了研究大疱性类天疱疮自身抗体的表位和亚类特异性，我们利用杆状病毒表达的BP180胞外区NH2和COOH末端区域的重组形式建立了一种酶联免疫吸附试验，并检测了116例活动期大疱性类天疱疮患者和100例对照组的血清。在116份大疱性类天疱疮血清中，93份(80%)和54份(47%)分别识别BP180胞外区的NH2和COOH末端区域。详细分析表明：(I)这种新的酶联免疫吸附试验具有高度的特异性(98%)和敏感性(93%)，因为116份大疱性类天疱疮血清中有108份与至少一种杆状病毒来源的重组体发生反应，(Ii)在活动性大疱性类天疱疮中，针对BP180胞外区NH2末端的自身抗体主要是Ig G(1)类，而对该区域的双重Ig G(1)和Ig G(4)与更严重的皮肤损害有关，(3)针对NH-末端和COOH-末端区域的自身反应在黏膜病变中更频繁地被检测到，(4)抗BP180胞外区NH2末端的抗体水平，但不能反映疾病的严重程度，提示抗NH2末端的自身抗体在大疱性类天疱疮发病机制中起关键作用。总之，这种新的酶联免疫吸附试验是一种快速诊断大疱性类天疱疮及相关疾病的高度敏感和特异的检测方法，并可能为大疱性类天疱疮患者的治疗提供预测参数。
Bullous pemphigoid, the most common autoimmune subepidermal bullous disorder, is associated with autoantibodies targeting antigenic sites clustered within the extracellular domain of BP180. To investigate epitope and subclass specificity of autoantibodies in bullous pemphigoid, we developed an enzyme-linked immunosorbent assay utilizing baculovirus-expressed recombinant forms of the NH2- and COOH-terminal regions of the extracellular domain of BP180 and examined sera obtained from patients with active bullous pemphigoid (n = 116) and controls (n = 100). Ninety-three (80%) and 54 (47%) of the 116 bullous pemphigoid sera recognized the NH2- and COOH-terminal regions, respectively, of the extracellular domain of BP180. Detailed analysis demonstrates that (i) this novel enzyme-linked immunosorbent assay is highly specific (98%) and sensitive (93%) as 108 of 116 bullous pemphigoid sera reacted with at least one of the baculovirus-derived recombinants, (ii) in active bullous pemphigoid, autoantibodies against the NH2- terminus of the extracellular domain of BP180 were predominantly of the IgG(1) class, whereas a dual IgG(1) and IgG(4) response to this region was related to a more severe skin involvement, (iii) autoreactivity against both the NH2- and COOH-terminal regions was more frequently detected in patients with mucosal lesions, and (iv) levels of IgG (and IgG(1)) against the NH2-terminal, but not against the COOH-terminal portion of the extracellular domain of BP180, reflected disease severity indicating that autoantibodies against the NH2-terminus are critical in the pathogenesis of bullous pemphigoid. In conclusion, this novel enzyme-linked immunosorbent assay represents a highly sensitive and specific assay for rapid diagnosis of bullous pemphigoid and related disorders and may provide predictive parameters for the management of bullous pemphigoid patients.