Role of autoantibodies against the linker subdomains of envoplakin and periplakin in the pathogenesis of paraneoplastic pemphigus
Role of autoantibodies against the linker subdomains of envoplakin and periplakin in the pathogenesis of paraneoplastic pemphigus
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DOI：
10.3760/cma.j.issn.0366-6999.2009.05.002
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发表时间：
2009-03-05
影响因子：
6.1
通讯作者：
Zhu Xue-jun
中科院分区：
文献类型：
--
作者：
Li Jing;Bu Ding-fang;Zhu Xue-jun
背景抗多种表皮蛋白自身抗体的存在是副肿瘤性天疱疮（PNP）的一个重要特征。循环抗桥粒芯糖蛋白3自身抗体是寻常型天疱疮（pemphigus vulgaris，PV）的主要致病性自身抗体，已被证实在PNR中具有致病性。由于PNP和PV之间存在许多临床差异，我们推测其他自身抗体参与PNR的发病机制，大多数PNP血清识别出Envoplakin（EPL）和Periplakin（PPL）。方法采用酶联免疫吸附试验（ELISA）和免疫荧光法检测PNP患者血清及肿瘤组织中抗EPL和PPL连接子结构域的自身抗体。结果用ELISA法检测到绝大多数PNP患者血清中存在抗EPL和PPL的自身抗体，肿瘤切除后抗EPL和PPL的自身抗体下降与临床症状的改善大致相当。培养的肿瘤细胞从PNP患者分泌这些自身抗体。在PNP肿瘤的B淋巴细胞上发现了EPL和PPL的特异性免疫球蛋白受体。结论抗EPL和抗PPL自身抗体也可能是PNR的致病性抗体
Background The presence of autoantibodies against multiple epidermal proteins is an important feature in paraneoplastic pemphigus (PNP). Circulating anti-desmoglein 3 autoantibody, the major pathogenic autoantibody in pemphigus vulgaris (PV), has been proved pathogenic in PNR Because of many clinical differences between PNP and PV, we speculate about the involvement of other autoantibodies in the pathogenesis of PNR Envoplakin (EPL) and periplakin (PPL) are recognized by most PNP sera. Their linker subdomains are highly homologous and necessary for the association of intermediate filaments.Methods We characterized the autoantibodies against the linker subdomains of EPL and PPL in PNP patients' sera and their associated tumors by enzyme-linked immunosorbent assay (ELISA) and immunofluorence. We also applied the purified autoantibodies against EPL and PPL from PNP sera to cultured human epidermal keratinocytes (HEK), to evaluate the changes of cell-cell adhesion.Results Autoantibodies against EPL and PPL were detected inmost PNP patients by ELISA, and the decrease of these autoantibodies after removal of the tumors was roughly comparable to the improvement of clinical symptoms. Cultured tumor cells from PNP patients secreted these autoantibodies. Specific immunoglobulin receptors for EPL and PPL were found on B lymphocytes in tumors from PNP. Furthermore, purified anti-EPL and anti-PPL autoantibodies from PNP sera were capable of dissociating cultured human epidermal keratinocytes.Conclusion Autoantibodies against EPL and PPL may also be pathogenic in PNR