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小柳原田病患者对黑素细胞特异性蛋白KU-MEL-1的频繁免疫反应。

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

作者信息

Otani S, Sakurai T, Yamamoto K, Fujita T, Matsuzaki Y, Goto Y, Ando Y, Suzuki S, Usui M, Takeuchi M, Kawakami Y

机构信息

Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, 35 Shinanomachi, Shinjyukuku, Tokyo, 160-8582, Japan.

出版信息

Br J Ophthalmol. 2006 Jun;90(6):773-7. doi: 10.1136/bjo.2005.086520. Epub 2006 Feb 15.

Abstract

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.

摘要

目的

分离可能参与Vogt-小柳-原田(VKH)病发病机制的自身抗原。

方法

通过用VKH患者血清筛选由黑素细胞和高色素性黑色素瘤细胞系构建的λ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。评估各种全葡萄膜炎患者和健康个体血清中针对自身抗原的IgG的存在情况。检查特异性IgG与各种临床病理特征之间的关系。

结果

KU-MEL-1是81个分离出的阳性克隆之一,代表35个不同基因,它是先前分离出的优先在黑素细胞中表达的黑色素瘤抗原。VKH患者血清中检测到的针对KU-MEL-1的IgG Ab量明显高于白塞病、结节病患者及健康个体血清中的量。血清KU-MEL-1 Ab阳性与HLA-DRB1*0405及男性VKH患者显著相关。

结论

KU-MEL-1被鉴定为VKH的一种新自身抗原。HLA-DRB1*0405阳性VKH患者中针对KU-MEL-1的IgG Ab的高频率诱导可能提示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。

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