Azuma Takeshi, Yamazaki Shiho, Yamakawa Akiyo, Ohtani Masahiro, Muramatsu Atsushi, Suto Hiroyuki, Ito Yoshiyuki, Dojo Manabu, Yamazaki Yukinao, Kuriyama Masaru, Keida Yoshihide, Higashi Hideaki, Hatakeyama Masanori
Second Department of Internal Medicine, Fukui Medical University, Fukui, Japan.
J Infect Dis. 2004 Mar 1;189(5):820-7. doi: 10.1086/381782. Epub 2004 Feb 2.
We investigated the relationship between the diversity of Helicobacter pylori CagA protein and clinical outcome. The cagA gene was sequenced in 115 clinical isolates. The binding affinity of CagA to Src homology 2 domain-containing tyrosine phosphatase (SHP-2) was examined by in vitro infection. Two major CagA subtypes were observed--the East Asian and the Western type. The grades of inflammation, activity of gastritis, and atrophy were significantly higher in patients with gastritis infected with the East Asian CagA-positive strain than in patients with gastritis infected with cagA-negative or Western CagA-positive strains. All strains isolated from patients with gastric cancer were East Asian CagA positive. East Asian CagA exhibited stronger SHP-2-binding activity than did Western CagA. These findings suggest that infection with East Asian CagA-positive H. pylori is associated with atrophic gastritis and gastric cancer and that persistent active inflammation induced by the East Asian CagA-positive strain may play a role in the pathogenesis of disease.
我们研究了幽门螺杆菌CagA蛋白多样性与临床结局之间的关系。对115株临床分离株的cagA基因进行了测序。通过体外感染检测CagA与含Src同源2结构域的酪氨酸磷酸酶（SHP-2）的结合亲和力。观察到两种主要的CagA亚型——东亚型和西方型。感染东亚CagA阳性菌株的胃炎患者的炎症分级、胃炎活动度和萎缩程度显著高于感染cagA阴性或西方CagA阳性菌株的胃炎患者。从胃癌患者中分离出的所有菌株均为东亚CagA阳性。东亚CagA比西方CagA表现出更强的SHP-2结合活性。这些发现表明，感染东亚CagA阳性幽门螺杆菌与萎缩性胃炎和胃癌有关，并且东亚CagA阳性菌株诱导的持续性活动性炎症可能在疾病发病机制中起作用。
