Expression of tumor-associated Thomsen-Friedenreich antigen (T Ag) in Helicobacter pylori and modulation of T Ag specific immune response in infected individuals

Expression of tumor-associated Thomsen-Friedenreich antigen (T Ag) in Helicobacter pylori and modulation of T Ag specific immune response in infected individuals
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DOI:
10.1081/imm-120016240
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发表时间:
2002-01-01
影响因子:
2.8
通讯作者:
Engstrand, L
Engstrand, L
中科院分区:
医学4区
文献类型:
--
作者:
Klaamas, K;Kurtenkov, O;Engstrand, L

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我们测试了胃癌相关细菌幽门螺杆菌 (H. pylori) 表达癌症相关 Thomsen-Friedenreich (T) 抗原的假设。我们还分析了幽门螺杆菌感染是否会改变患者血清中天然抗 T 抗体的数量。使用五种不同的 T 抗原特异性单克隆抗体 (MAb),通过免疫印迹和细胞 ELISA 分析幽门螺杆菌 NCTC 1163 7 菌株和幽门螺杆菌临床分离株 (n = 13) 的细胞表面膜提取物。与 68 kDa 和 58 kDa 相似的两个主要蛋白条带在幽门螺杆菌提取物的印迹上用 T 特异性 MAb 进行了免疫染色,但没有用不相关的 MAb 进行了免疫染色。其特异性在于用花生凝集素(PNA)和兔T抗原抗血清阻断免疫染色。 T 特异性 MAb 与 58 kDa 蛋白带的结合也被针对幽门螺杆菌热休克蛋白的兔抗血清阻断。 T 抗原相关蛋白的相对表达在幽门螺杆菌菌株之间存在差异,68 M 相关 T 抗原表达在病理更严重的患者中更高。比较胃癌患者(n = 66)和正常献血者(n = 62)的抗T表位IgG抗体水平,胃癌患者抗T Ab水平显着低于正常献血者。在H. pylori感染的正常献血者中,血清T特异性抗体与H. pylori IgG抗体水平呈显着正相关(P < 0.001),但在H. pylori感染的癌症患者中未发现这种相关性。总之,癌症相关的 T 表位在幽门螺杆菌中表达,并且幽门螺杆菌感染个体中 T 抗原特异性免疫应答的调节表明幽门螺杆菌感染可能会改变针对癌症的天然免疫机制。
We tested the hypothesis that the gastric cancer associated bacteria, Helicobacter pylori (H. pylori) express the cancer-related Thomsen-Friedenreich (T) antigen. We also analysed whether infection with H. pylori alters the amount of natural anti-T antibodies in the patients' sera. Cell surface membrane extracts of H. pylori NCTC 1163 7 strain and clinical isolates of H. pylori (n = 13) were analysed by immunoblotting and cell-ELISA with five different T antigen-specific monoclonal antibodies (MAbs). Two major protein bands of similar to68 kDa and 58 kDa, were immunostained on blots of H. pylori extracts with T specific MAbs but not immunostained with unrelated MAb. The specificity was shown in that immunostaining was blocked with peanut agglutinin (PNA) and rabbit antiserum to T antigen. The binding of T specific MAb to the 58 kDa protein band was also blocked by rabbit antiserum against heat shock proteins of H. pylori. The relative expression of T antigen-related proteins differed among H. pylori strains, with 68 M associated T antigen expression higher in patients with more severe pathology. The level of IgG antibody to T epitope in patients with gastric cancer (n = 66) and normal blood donors (n = 62) were compared and the level of anti-T Ab in gastric cancer patients was significantly lower than that in normal blood donors. A significant positive correlation between T specific antibody in serum and H. pylori IgG antibody level was found in H. pylori-infected normal blood donors (P < 0.001), but this correlation was not found in H. pylori-infected cancer patients. In summary, the cancer related T epitope is expressed in H. pylori and modulation of T antigen-specific immune response in H. pylori-infected individuals suggests that H. pylori infection may alter natural immune mechanisms against cancer.