Analysis of the antibody repertoire of astrocytoma patients against antigens expressed by gliomas
Analysis of the antibody repertoire of astrocytoma patients against antigens expressed by gliomas
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DOI：
10.1002/ijc.10170
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发表时间：
2002-03-01
影响因子：
6.4
通讯作者：
Pfreundschuh, M
中科院分区：
文献类型：
--
作者：
Schmits, R;Cochlovius, B;Pfreundschuh, M
优先或专门表达的星形细胞瘤和自体免疫系统识别的抗原的分子表征是特异性疫苗的发展的先决条件。为了鉴定这些抗原，我们使用SEREX（通过重组cDNA表达克隆进行抗原的血清学鉴定）筛选了5个来源于星形细胞瘤和其他胶质瘤的cDNA表达文库，用于与星形细胞瘤患者血清中的高滴度IgG抗体反应。用18名星形细胞瘤患者的血清对>5 X 10（6）个克隆进行自体和同种异体SEREX分析，发现10种抗原：分化抗原胶质细胞酸性蛋白（GFAP）、胶质细胞增殖抑制因子I（其在所有测试的胶质瘤样品中过表达）、3种参与基因表达和增殖调节的其他分子（nm 23-H2编码的核苷二磷酸激酶B、Ran结合蛋白2和son基因编码的DNA结合蛋白）、补体抑制分子SP 40、40、伴侣蛋白TCP-1、钙连接蛋白和2种新的基因产物。没有检测到针对在神经胶质瘤中定期表达的“共享肿瘤”或“癌症睾丸抗原”的免疫应答。星形细胞瘤患者对神经胶质瘤表达的抗原的抗体反应是罕见的，除了β-抑制剂I和儿子基因的产物，也发现在明显健康的对照。我们的结论是，虽然星形细胞瘤表达了广泛的抗原，他们很少引起抗体反应，最有可能是因为其内在的免疫抑制作用。(C)2002 Wiley-Liss，Inc.
The molecular characterization of antigens preferentially or exclusively expressed by astrocytomas and recognized by the autologous immune system are a prerequisite for the development of specific vaccines. To identify such antigens, we screened 5 cDNA expression libraries derived from astrocytomas and other gliomas for reactivity with high-titered IgG antibodies in the sera of astrocytoma patients using SEREX, the serologic identification of antigens by recombinant cDNA expression cloning. Autologous and allogeneic SEREX analysis of >5 X 10(6) clones with the sera of 18 astrocytoma patients revealed 10 antigens: the differentiation antigen glial fibrillary acidic protein (GFAP), Bax-inhibitor I (which was overexpressed in all glioma samples tested), 3 other molecules involved in the regulation of gene expression and proliferation (the nm23-H2-encoded nucleoside diphosphate kinase B, the Ran binding protein-2 and a DNA binding protein encoded by the son gene), SP40,40 (a complement inhibitory molecule), the chaperonin TCP-1, calnexin and 2 new gene products. No immune responses were detected against the "shared tumor" or "cancer testis antigens" that are regularly expressed in gliomas. Antibody responses in astrocytoma patients against antigens expressed by gliomas were rare and, with the exception of Bax-inhibitor I and the product of the son gene, were also found in apparently healthy controls. We conclude that although astrocytomas express a broad spectrum of antigens, they elicit antibody responses only rarely, most likely because of their intrinsic immunosuppressive effects. (C) 2002 Wiley-Liss, Inc.