ANTIBASEMENT MEMBRANE AUTOANTIBODIES IN PATIENTS WITH ANTI-EPILIGRIN CICATRICIAL PEMPHIGOID BIND THE ALPHA-SUBUNIT OF LAMININ-5
ANTIBASEMENT MEMBRANE AUTOANTIBODIES IN PATIENTS WITH ANTI-EPILIGRIN CICATRICIAL PEMPHIGOID BIND THE ALPHA-SUBUNIT OF LAMININ-5
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DOI：
10.1111/1523-1747.ep12323431
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发表时间：
1995-10-01
影响因子：
6.5
通讯作者：
YANCEY, KB
中科院分区：
文献类型：
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作者：
KIRTSCHIG, G;MARINKOVICH, MP;YANCEY, KB
最近的研究发现，一组瘢痕性类天疱疮患者具有 IgG 抗基底膜自身抗体，可以识别 Epiligrin，这是一组二硫键连接的多肽，与层粘连蛋白 5（以前称为 Kalinin、Nicein 或 BM600）密切相关，甚至不相同。为了进一步了解这些患者水疱形成的病理生理学，我们试图鉴定其自身抗体靶向的特定多肽。比较研究表明，来自这些患者（九人中的九人）的血清、P1E1 单克隆抗 Epiligrin 抗体以及多克隆和单克隆抗层粘连蛋白 5 抗体可免疫沉淀来自生物合成放射性标记的人角质形成细胞培养基的同一组二硫键连接的多肽。此外，9 名抗 Epiligrin 瘢痕性类天疱疮患者中的 8 名患者的血清对层粘连蛋白 5 的 α 亚基进行了免疫印迹，但未显示对其 β 或 γ 亚基有反应性。此外，来自代表性患者的循环 IgG 针对层粘连蛋白 5 的 α 亚基进行亲和纯化，并显示以与来自所有抗 Epiligrin 瘢痕性类天疱疮患者的自身抗体相同的方式结合 1 M 氯化钠裂片皮肤的真皮侧。在免疫沉淀或免疫印迹实验中，大疱性类天疱疮 (n = 5)、其他形式的瘢痕性类天疱疮 (n = 5)、获得性大疱性表皮松解症 (n = 4) 或大疱性系统性红斑狼疮 (n = 1) 患者的血清未显示出针对该层粘连蛋白亚型的任何亚基的反应性。这些发现与先前的报道相关，该报道表明针对层粘连蛋白 5 的 α 亚基（即层粘连蛋白 α 3 亚基）的单克隆抗体可诱导人角质形成细胞在体外与细胞外基质分离以及原位与人皮肤表皮分离。总之，这些研究表明层粘连蛋白亚基 α3 介导基底角质形成细胞与表皮基底膜的附着，并且针对它的自身抗体可能是致病性的。
Recent studies have identified a group of cicatricial pemphigoid patients who have IgG anti-basement membrane autoantibodies that recognize epiligrin, a set of disulfide-linked polypeptides closely related if not identical to laminin 5 (formerly called kalinin, nicein, or BM600). To further understand the pathophysiology of blister formation in these patients, we have sought to identify the specific polypeptide(s) targeted by their autoantibodies. Comparative studies show that sera from these patients (nine of nine), P1E1 monoclonal anti-epiligrin antibody, and polyclonal as well as monoclonal anti-laminin 5 antibodies immunoprecipitate the same set of disulfide-linked polypeptides from media of biosynthetically radiolabeled human keratinocytes. Moreover, sera from eight of nine patients with anti-epiligrin cicatricial pemphigoid immunoblot the alpha subunit of laminin 5 but show no reactivity to its beta or gamma subunits. In addition, circulating IgG from a representative patient was affinity-purified against the alpha subunit of laminin 5 and shown to bind the dermal side of 1 M NaCl split skin in the same manner as autoantibodies from all patients with anti-epiligrin cicatricial pemphigoid. Sera from patients with bullous pemphigoid (n = 5), other forms of cicatricial pemphigoid (n = 5), epidermolysis bullosa acquisita (n = 4), or bullous systemic lupus erythematosus (n = 1) show no reactivity against any subunit of this laminin isoform in immunoprecipitation or immunoblot experiments. These findings correlate with prior reports showing that a monoclonal antibody directed against the alpha subunit of laminin 5 (i.e., laminin subunit alpha 3) induces detachment of human keratinocytes from extracellular matrix in vitro as well as epidermis from human skin in situ. Together, these studies suggest that laminin subunit alpha 3 mediates attachment of basal keratinocytes to epidermal basement membrane and that autoantibodies directed against it may be pathogenic.