Link Alexander, Langner Cosima, Schirrmeister Wiebke, Habendorf Wiebke, Weigt Jochen, Venerito Marino, Tammer Ina, Schlüter Dirk, Schlaermann Philipp, Meyer Thomas F, Wex Thomas, Malfertheiner Peter
Alexander Link, Cosima Langner, Wiebke Schirrmeister, Wiebke Habendorf, Jochen Weigt, Marino Venerito, Thomas Wex, Peter Malfertheiner, Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, Magdeburg, 39120 Magdeburg, Germany.
World J Gastroenterol. 2017 Jul 14;23(26):4712-4723. doi: 10.3748/wjg.v23.i26.4712.
To evaluate the frequency of () CagA antibodies in infected subjects and to identify potential histopathological and bacterial factors related to CagA-immune response.
Systematic data to isolates, blood samples, gastric biopsies for histological and molecular analyses were available from 99 prospectively recruited subjects. Serological profile (anti-, anti-CagA) was correlated with isolates (, EPIYA, genotype), histology (Sydney classification) and mucosal interleukin-8 (IL-8) mRNA and protein expression. Selected strains were assessed for CagA protein expression and IL-8 induction in co-cultivation model with AGS cells.
Thirty point three percent of microbiologically confirmed infected patients were seropositive for CagA. Majority of isolates were gene positive (93.9%) with following polymorphisms: 42.4% , 23.2% and 34.3% . Anti-CagA-IgG seropositivity was strongly associated with atrophic gastritis, increased mucosal inflammation according to the Sydney score, IL-8 and mRNA expression. and polymorphisms were the major determinants for positive ( s1m1) or negative ( s2m2) anti-CagA serological immune response, which also correlated with the inflammatory potential in AGS cells. co-cultivation of representative strains with AGS cells confirmed functional CagA translocation, which showed only partial correlation with CagA seropositivity in patients, supporting as major co-determinant of the immune response.
Serological immune response to + strain in infected patients is strongly associated with polymorphism, suggesting the crucial role of bacterial factors in immune and clinical phenotype of the infection.
评估幽门螺杆菌（Hp）感染患者中细胞毒素相关基因A（CagA）抗体的频率，并确定与CagA免疫反应相关的潜在组织病理学和细菌学因素。
从99名前瞻性招募的受试者中获得了关于Hp分离株、血液样本、用于组织学和分子分析的胃活检的系统数据。血清学特征（抗Hp、抗CagA）与Hp分离株（vacA、EPIYA、cagA基因型）、组织学（悉尼分类）以及黏膜白细胞介素-8（IL-8）mRNA和蛋白表达相关。在与AGS细胞的共培养模型中，对选定的Hp菌株进行CagA蛋白表达和IL-8诱导评估。
30.3%经微生物学确诊的Hp感染患者CagA血清学阳性。大多数Hp分离株cagA基因阳性（93.9%），具有以下多态性：42.4% s1m1、23.2% s2m2和34.3% s3m2。抗CagA-IgG血清学阳性与萎缩性胃炎、根据悉尼评分的黏膜炎症增加、IL-8和cagA mRNA表达密切相关。s1m1和s2m2多态性是抗CagA血清学免疫反应阳性（s1m1）或阴性（s2m2）的主要决定因素，这也与AGS细胞中的Hp炎症潜能相关。代表性Hp菌株与AGS细胞的共培养证实了功能性CagA易位，其与患者中CagA血清学阳性仅部分相关，支持cagA作为免疫反应的主要共同决定因素。
Hp感染患者对cagA+菌株的血清学免疫反应与cagA多态性密切相关，提示细菌因素在该感染的免疫和临床表型中起关键作用。
