AUTOANTIBODIES TO DESMOPLAKIN-I AND DESMOPLAKIN-II IN PATIENTS WITH ERYTHEMA-MULTIFORME
AUTOANTIBODIES TO DESMOPLAKIN-I AND DESMOPLAKIN-II IN PATIENTS WITH ERYTHEMA-MULTIFORME
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DOI：
10.1084/jem.181.1.169
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发表时间：
1995-01-01
影响因子：
15.3
通讯作者：
RAPPERSBERGER, K
中科院分区：
文献类型：
--
作者：
FOEDINGER, D;ANHALT, GJ;RAPPERSBERGER, K
多形性红斑(EM)是一种慢性复发性炎症性皮肤病综合征。根据皮肤和粘膜受累的严重程度和程度，可将其定义为EM轻度或EM重度。在这项研究中，我们证明了桥粒斑块的两种主要蛋白--桥粒蛋白I和桥粒蛋白II的自身抗体(AABS)在6名EM重度变异型EM患者中的6名患者中存在。皮损皮肤和粘膜的光镜研究沿着角质形成细胞的细胞膜，定位于体内结合的免疫球蛋白G(IgG)，呈点状桥粒图案。免疫电子显微镜显示，体内结合的免疫球蛋白仅局限于桥粒斑块。这些发现得到了间接免疫定位研究的证实，这些研究表明在活动期疾病患者的血清中存在Ig G AABS。这些AABS不仅能结合到与特定的鼠抗桥粒蛋白I和II单抗共定位的上皮细胞桥粒斑块上，还能标记心肌细胞的间盘。循环免疫球蛋白AABS的生化鉴定表明桥粒蛋白I和II是真正的靶标自身抗原。通过将血清被动转移到新生小鼠体内，显示了血清AABS与角质形成细胞的结合。本研究结果提示某些EM患者存在体液免疫反应，提示抗桥粒蛋白I和桥粒蛋白II的AABS在本病中具有潜在的致病作用。
Erythema multiforme (EM) represents a syndrome of chronic recurrent inflammatory skin disease. Depending on the severity and extent of skin and mucosal involvement, it is defined either as EM minor or EM major. In this study we demonstrate the presence of autoantibodies (aAbs) against desmoplakin I and II, two major proteins of the desmosomal plaque, in six of six patients with the severe variant of EM, EM major. Light microscopic studies of lesional skin and mucous membranes localized in vivo bound immunoglobulin G (IgG) in a dotted desmosomal pattern along the cytoplasmic membranes of keratinocytes. By immunoelectronmicroscopy, in vivo bound IgG was confined to the desmosomal plaques. These findings were confirmed by indirect immunolocalization studies that demonstrated the presence of IgG aAbs in the serum of patients during active disease. These aAbs did not only bind to desmosomal plaques of epithelial cells where they colocalized with defined murine monoclonal antibodies directed against desmoplakin I and II, but also labeled the intercalated discs of myocardial cells. Biochemical characterization of circulating IgG aAbs revealed desmoplakin I and II as actual target autoantigens. By passive transfer of serum into newborn mice, in vivo binding of serum aAbs to keratinocytes was shown. The findings presented in this study imply a humoral immune response in certain patients with EM major and indicate a potential pathogenetic role of aAbs against desmoplakin I and II in this disease.