Frequent immune response to a melanocyte specific protein KU-MEL-1 in patients with Vogt-Koyanagi-Harada disease

Frequent immune response to a melanocyte specific protein KU-MEL-1 in patients with Vogt-Koyanagi-Harada disease
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DOI:
10.1136/bjo.2005.086520
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发表时间:
2006-02
影响因子:
4.1
通讯作者:
Soshi otani;Toshiharu Sakurai;Kazuhiko Yamamoto;T. Fujita;Yuriko Matsuzaki;Yasufumi Goto;Yasutaka Ando;Saburosuke Suzuki;Masahiko Usui;Masaru Takeuchi;Yutaka Kawakami
Soshi otani;Toshiharu Sakurai;Kazuhiko Yamamoto;T. Fujita;Yuriko Matsuzaki;Yasufumi Goto;Yasutaka Ando;Saburosuke Suzuki;Masahiko Usui;Masaru Takeuchi;Yutaka Kawakami
中科院分区:
医学2区
文献类型:
--
作者:
Soshi otani;Toshiharu Sakurai;Kazuhiko Yamamoto;T. Fujita;Yuriko Matsuzaki;Yasufumi Goto;Yasutaka Ando;Saburosuke Suzuki;Masahiko Usui;Masaru Takeuchi;Yutaka Kawakami

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目的:分离可能参与 Vogt-Koyanagi-Harada (VKH) 病发病机制的自身抗原。方法:通过用患者血清筛选黑色素细胞和高度色素化黑色素瘤细胞系制成的 lambda 噬菌体 cDNA 文库,分离出 VKH 患者血清中免疫球蛋白 G 抗体 (IgG Ab) 识别的自身抗原。对患有各种全葡萄膜炎的患者和健康个体的血清中自身抗原特异性 IgG 的存在进行了评估。检查了特异性 IgG 与各种临床病理特征之间的关系。结果:KU-MEL-1被发现是代表35个不同基因的81个分离的阳性克隆之一,它是先前分离的黑色素瘤抗原,优先在黑色素细胞中表达。在 VKH 患者血清中检测到的 KU-MEL-1 特异性 IgG Ab 含量显着高于白塞氏病、结节病患者和健康个体的血清。血清 KU-MEL-1 Ab 阳性与 HLA-DRB1*0405 和男性 VKH 患者显着相关。结论:KU-MEL-1被鉴定为VKH的新自身抗原。 HLA-DRB1*0405 阳性 VKH 患者中频繁诱导 KU-MEL-1 IgG 抗体可能表明 KU-MEL-1 特异性 CD4+ T 细胞可能参与 VKH 的发病机制,这表明其可能用于开发 VKH 患者的诊断和治疗方法。
Aim: To isolate autoantigens possibly involved in the pathogenesis of Vogt-Koyanagi-Harada (VKH) disease. Methods: Autoantigens recognised by immunoglobulin G antibodies (IgG Ab) in sera from VKH patients were isolated by screening the lambda phage cDNA libraries made from melanocytes and a highly pigmented melanoma cell line with the patients’ sera. Presence of IgG specific for the autoantigens in sera from patients with various panuveitis and healthy individuals was evaluated. Relation between the specific IgG and various clinicopathological features was examined. Results: KU-MEL-1 was found to be one of the 81 isolated positive clones representing 35 distinct genes, which is a previously isolated melanoma antigen preferentially expressed in melanocytes. The IgG Ab specific for KU-MEL-1 was detected in sera from patients with VKH in significantly higher amounts than in sera from patients with Behçet’s disease, sarcoidosis, and from healthy individuals. Positive serum KU-MEL-1 Ab was significantly associated with HLA-DRB1*0405 and male VKH patients. Conclusion: KU-MEL-1 was identified as a new autoantigen for VKH. The highly frequent induction of IgG Ab for KU-MEL-1 in HLA-DRB1*0405 positive VKH patients may suggest the possible involvement of KU-MEL-1 specific CD4+ T cells in the pathogenesis of VKH, suggesting the possible use in the development of diagnostic and therapeutic treatments for VKH patients.