Laminin-6 and laminin-5 are recognized by autoantibodies in a subset of cicatricial pemphigoid.
Laminin-6 and laminin-5 are recognized by autoantibodies in a subset of cicatricial pemphigoid.
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疤痕性类天疱疮亚型中的层粘连蛋白 6 和层粘连蛋白 5 可被自身抗体识别。
DOI：
10.1111/1523-1747.ep12292578
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
Marinkovich,MP
中科院分区：
文献类型：
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作者：
Chan,LS;Majmudar,AA;Tran,HH;Meier,F;Schaumburg-Lever,G;Chen,M;Anhalt,G;Woodley,DT;Marinkovich,MP
我们的特点是基底膜区（BMZ）的自身抗原靶向的自身抗体（AAb）从瘢痕性类天疱疮患者。严重口腔瘢痕性类天疱疮患者的血清中含有IgG抗BMZ AAb。AAb标记盐裂皮肤上的较低BMZ组分，并通过直接和间接免疫电子显微镜（HEM）定位于较低的透明层/致密层，但不标记血管。AAb不与EHS层粘连蛋白-1和IV型胶原、胃蛋白酶化的人IV型胶原、重组巢蛋白或VII型胶原的NC 1结构域通过斑点印迹和蛋白质印迹反应。由于层粘连蛋白-5被鉴定为瘢痕性类天疱疮的自身抗原，我们将研究重点放在层粘连蛋白家族上。通过蛋白质印迹法研究了来自正常角质形成细胞（含有层粘连蛋白-6和层粘连蛋白-5）和JEB角质形成细胞（含有层粘连蛋白-6但不含层粘连蛋白-5）的培养条件培养基。在非还原条件下，患者的AAb识别600 kDa的蛋白质（层粘连蛋白-6）强烈和400 kDa的蛋白质（层粘连蛋白-5）弱正常角质形成细胞培养基中，即使丰富的层粘连蛋白-5存在。然而，在JEB角质形成细胞培养基中，600 kDa蛋白（层粘连蛋白-6）单独被患者的AAb识别。AAb还免疫标记了缺乏层粘连蛋白-5的JEB皮肤的BMZ。来自该患者和另外两名患有抗层粘连蛋白-5瘢痕性类天疱疮的患者的AAb免疫沉淀层粘连蛋白-6和4层粘连蛋白-5。总之，IEM、非还原性蛋白质印迹、免疫沉淀和JEB皮肤BMZ免疫标记的结果表明，层粘连蛋白-6以及层粘连蛋白-5通过来自瘢痕性类天疱疮患者亚组的AAb鉴定。我们建议这个子集的名称为“抗层粘连蛋白瘢痕性类天疱疮”。
We characterized basement membrane zone (BMZ) autoantigens targeted by autoantibodies (AAb) from patients with cicatricial pemphigoid. Serum from a patient with severe oral cicatricial pemphigoid contained IgG anti-BMZ AAb. The AAb labeled a lower BMZ component on salt-split skin and localized to the lower lamina lucida/lamina densa by direct and indirect immunoelectron microscopy (HEM) but did not label blood vessels. The AAb did not react with EHS laminin-1 and type IV collagen, pepsinized human type IV collagen, recombinant entactin, or NC1 domain of type VII collagen by dot blotting and western blotting. We focused our studies on the laminin family, as laminin-5 was identified as an autoantigen in cicatricial pemphigoid. Culture-conditioned media from normal keratinocytes (containing laminin-6 and laminin-5) and JEB keratinocytes (containing laminin-6 but not laminin-5) were studied by western blotting. Under nonreducing conditions, the patient's AAb recognized a 600-kDa protein (laminin-6) intensely and a 400-kDa protein (laminin-5) weakly in normal keratinocyte medium even though abundant laminin-5 was present. In JEB keratinocyte medium, however, the 600-kDa protein (laminin-6) alone was recognized by the patient's AAb. The AAb also immunolabeled BMZ of JEB skin that lacked laminin-5. The AAb from this patient and two other patients with anti-laminin-5 cicatricial pemphigoid immunoprecipitated both laminin-6 an4 laminin-5. Taken together, the results of IEM, non-reducing western blotting, immunoprecipitation, and JEB skin BMZ immunolabeling indicate that laminin-6, as well as laminin-5, is identified by the AAb from a subset of cicatricial pemphigoid patients. We propose the name “anti-laminin cicatricial pemphigoid” for this subset.