Autoantibodies in a subgroup of patients with linear IgA disease react with the NC16A domain of BP1801.
Autoantibodies in a subgroup of patients with linear IgA disease react with the NC16A domain of BP1801.
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DOI：
10.1046/j.1523-1747.1999.00808.x
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发表时间：
1998-03
期刊：
影响因子：
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通讯作者：
D. Zillikens;K. Herzele;M. Georgi;E. Schmidt;I. Chimanovitch;E. Bröcker;H. Schumann;J. Mascaró;L. Diaz;Leena Bruckner-Tuderman;G. Giudice
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文献类型：
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作者：
D. Zillikens;K. Herzele;M. Georgi;E. Schmidt;I. Chimanovitch;E. Bröcker;H. Schumann;J. Mascaró;L. Diaz;Leena Bruckner-Tuderman;G. Giudice
线状IgA病是一种自身免疫性皮下水疱病，其特征是皮肤基底膜区有IgA沉积。来自线性IgA病血清的IGA抗体与97 kDa(LABD97)和120 kDa(LAD-1)的抗原反应，这两个抗原似乎都是大疱性类天疱疮180(XVI型胶原)细胞外域的片段。本研究的目的是确定线性IgA病血清是否与BP180的免疫优势区域(NC16A结构域)发生反应，该区域是大疱性类天疱疮患者产生的免疫球蛋白自身抗体的主要靶点。事实上，50份线性IgA病血清中有11份被发现含有通过免疫印迹识别重组形式NC16A的IgA自身抗体。酶联免疫吸附试验表明，相同的血清也能与NC16A反应。表位映射分析发现了位于NC16A N端45个氨基酸的4个线性IgA疾病相关表位，所有这些表位都曾被确定为大疱性类天疱疮自身抗体的靶点。对NC16A反应的线性IgA病血清中有8份也能识别SCC-25细胞株分泌的LAD-1，5份血清能识别角质形成细胞中提取的BP180。免疫吸附去除了对NC16A的反应性的线性IgA病血清通过免疫印迹继续与LAD-1抗原和BP180反应，并在间接免疫荧光显微镜下与基膜带反应。我们的结果表明，来自线性IgA疾病患者子集的IgA自身抗体与大疱性类天疱疮中的免疫球蛋白自身抗体靶向的BP180上的相同部位发生反应。
Linear IgA disease is an autoimmune subepidermal blistering disease characterized by IgA deposits at the cutaneous basement membrane zone. IgA antibodies from linear IgA disease sera react with antigens of 97 kDa (LABD97) and 120 kDa (LAD-1), both of which appear to be fragments of the extracellular domain of bullous pemphigoid 180 (type XVII collagen). The aim of this study was to determine whether linear IgA disease sera react with the immunodominant region of BP180 (NC16A domain), which is a major target of IgG autoantibodies produced by patients with bullous pemphigoid. Indeed, 11 of 50 linear IgA disease sera were found to contain IgA autoantibodies that recognized a recombinant form of NC16A by immunoblotting. The same sera also reacted with NC16A by enzyme-linked immunosorbent assay. An epitope mapping analysis uncovered four linear IgA disease-associated epitopes located within the 45 amino acid N-terminal stretch of NC16A, all of which were previously identified as antigenic sites targeted by bullous pemphigoid autoantibodies. Eight of the linear IgA disease sera that were reactive with NC16A also recognized LAD-1 secreted by the SCC-25 cell line, and five sera recognized BP180 extracted from keratinocytes. Linear IgA disease sera depleted of reactivity to NC16A by immunoadsorption continued to react with both the LAD-1 antigen and BP180 by immunoblotting and with the basement membrane zone by indirect immunofluorescence microscopy. Our results demonstrate that IgA autoantibodies from a subset of linear IgA disease patients react with the same sites on BP180 that are targeted by IgG autoantibodies in bullous pemphigoid.