Appelmelk B J, Simoons-Smit I, Negrini R, Moran A P, Aspinall G O, Forte J G, De Vries T, Quan H, Verboom T, Maaskant J J, Ghiara P, Kuipers E J, Bloemena E, Tadema T M, Townsend R R, Tyagarajan K, Crothers J M, Monteiro M A, Savio A, De Graaff J
Department of Medical Microbiology, Vrije Universiteit Medical School and Academic Hospital, Amsterdam, The Netherlands.
Infect Immun. 1996 Jun;64(6):2031-40. doi: 10.1128/iai.64.6.2031-2040.1996.
Helicobacter pylori is involved in gastritis, gastric and duodenal ulcers, gastric adenocarcinoma, and mucosa-associated lymphoid tissue lymphoma. Earlier studies already suggested a role for autoimmune phenomena in H. pylori-linked disease. We now report that lipopolysaccharides (LPS) of H. pylori express Lewis y, Lewis x, and H type I blood group structures similar to those commonly occurring in gastric mucosa. Immunization of mice and rabbits with H. pylori cells or purified LPS induced an anti-Lewis x or y or anti-H type I response, yielding antibodies that bound human and murine gastric glandular tissue, granulocytes, adenocarcinoma, and mucosa-associated lymphoid tissue lymphoma cells. Experimental oral infections in mice or natural infection in humans yielded anti-Lewis antibodies also. The beta chain of gastric (H+,K+)-ATPase, the parietal cell proton pump involved in acid secretion, contained Lewis y epitopes; gastric mucin contained Lewis x and y antigenic determinants. Growth in mice of a hybridoma that secretes H. pylori-induced anti-Lewis y monoclonal antibodies resulted in histopathological evidence of gastritis, which indicates a direct pathogenic role for anti-Lewis antibodies. In conclusion, our observations demonstrate that molecular mimicry between H. pylori LPS and the host, based on Lewis antigens, and provide understanding of an autoimmune mechanism for H. pylori-associated type B gastritis.
幽门螺杆菌与胃炎、胃和十二指肠溃疡、胃腺癌以及黏膜相关淋巴组织淋巴瘤有关。早期研究已表明自身免疫现象在幽门螺杆菌相关疾病中起作用。我们现在报告，幽门螺杆菌的脂多糖（LPS）表达与胃黏膜中常见的Lewis y、Lewis x和H I型血型结构相似。用幽门螺杆菌细胞或纯化的LPS免疫小鼠和兔子会诱导产生抗Lewis x或y或抗H I型反应，产生能与人及小鼠胃腺组织、粒细胞、腺癌和黏膜相关淋巴组织淋巴瘤细胞结合的抗体。小鼠的实验性口服感染或人类的自然感染也会产生抗Lewis抗体。胃（H⁺，K⁺）-ATP酶的β链（参与胃酸分泌的壁细胞质子泵）含有Lewis y表位；胃黏液含有Lewis x和y抗原决定簇。分泌幽门螺杆菌诱导的抗Lewis y单克隆抗体的杂交瘤在小鼠体内生长导致了胃炎的组织病理学证据，这表明抗Lewis抗体具有直接致病作用。总之，我们的观察结果表明基于Lewis抗原的幽门螺杆菌LPS与宿主之间存在分子模拟，并为幽门螺杆菌相关B型胃炎的自身免疫机制提供了理解。
