HPGC Research Group, Department of Medical Biotechnology, Pasteur Institute of Iran, Tehran, Iran.
Gastroenterology Department, Amiralam Hospital, Tehran University of Medical Sciences, Tehran, Iran.
Microb Pathog. 2018 Jun;119:137-144. doi: 10.1016/j.micpath.2018.04.018. Epub 2018 Apr 14.
Helicobacter pylori express a large array of antigens, each of which is duly responsible for successful colonization and pathogenesis. Here, we have studied host serum antibody responses to four of its immunodominant antigens in association with the infection status and the resulting clinical outcomes.
For this purpose, four individual H. pylori proteins (UreB, CagA, Tip-α and HP0175) were produced in recombinant forms. Serum antibody responses of 246 (75 GC and 171 NUD) patients, against the above antigens, were evaluated by multiplex immunoblotting. The associations between the resulting data and the infection status, as well as clinical outcomes were evaluated using logistic regression models.
Serum antibodies to all four recombinant antigens increased the chances of detecting screening ELISA-positive subjects, in an escalating dose-dependent manner, ranging from 2.6 (1.5-4.7) for HP0175 to 14.3 for UreB (4.3-50.7), exhibiting the lowest and highest odds ratios, respectively (P ≤ 0.001), such that 98.2% of the subjects with antibodies to all four antigens, were also positive by the screening ELISA (P < 0.0001). Among the screening ELISA-positive subjects, the three antigens of CagA, Tip-α, and HP0175 were able to segregate current from past H. pylori infection (P < 0.05). Accordingly, subjects with antibodies to one or more antigen(s) were at 5.4 (95% CI: 1.8-16.4) folds increased chances of having current infection, as compared to triple negatives (P = 0.003). In reference to the clinical outcomes, those with serum antibodies to CagA were more prevalent among gastric cancer, as compared to NUD patients (OR: 5.4, 95% CI: 2.4-12.2, P < 0.0001). When NUD patients were categorized according to their histopathologic status, multiple antigen analysis revealed that subjects with serum antibodies to one or more of the 3 current infection-positive antigens (CagA, Tip-α, and HP0175) were at 9.7 (95% CI: 2.1-44.9, P = 0.004) folds increased risk of atrophic gastritis, in reference to triple negatives.
The non-invasive multiplex serology assay, presented here, was able to not only detect subjects with current H. pylori infection, it could also screen dyspeptic patients for the presence of gastric atrophy. This simple and cost-efficient method can supplement routine screening ELISAs, to increase the chances of detecting current infections as well as atrophic gastritis.
幽门螺杆菌表达大量的抗原，每一种抗原都对成功定植和发病机制负有责任。在这里，我们研究了其四种免疫优势抗原的宿主血清抗体反应与感染状况及由此产生的临床结果之间的关系。
为此，我们以重组形式产生了四种单独的幽门螺杆菌蛋白（UreB、CagA、Tip-α和 HP0175）。通过多重免疫印迹法评估了 246 名（75 名 GC 和 171 名 NUD）患者对上述抗原的血清抗体反应。使用逻辑回归模型评估了所得数据与感染状况和临床结果之间的关联。
血清对所有四种重组抗原的抗体均以递增剂量依赖性的方式增加了检测筛查 ELISA 阳性受试者的可能性，范围从 HP0175 的 2.6（1.5-4.7）到 UreB 的 14.3（4.3-50.7），分别具有最低和最高的比值比（P≤0.001），因此，98.2%的对所有四种抗原均有抗体的受试者也通过筛查 ELISA 呈阳性（P<0.0001）。在筛查 ELISA 阳性的受试者中，CagA、Tip-α 和 HP0175 这三种抗原能够区分当前和过去的幽门螺杆菌感染（P<0.05）。因此，与三阴性相比，对一种或多种抗原有抗体的受试者感染的可能性增加了 5.4 倍（95%CI：1.8-16.4）（P=0.003）。在参考临床结果时，与 NUD 患者相比，胃癌患者中 CagA 血清抗体更为常见（比值比：5.4，95%CI：2.4-12.2，P<0.0001）。当根据组织病理学状态对 NUD 患者进行分类时，多抗原分析显示，对三种当前感染阳性抗原（CagA、Tip-α和 HP0175）中的一种或多种有血清抗体的受试者发生萎缩性胃炎的风险增加了 9.7 倍（95%CI：2.1-44.9，P=0.004），与三阴性相比。
本文介绍的非侵入性多重血清学检测不仅能够检测当前的幽门螺杆菌感染患者，还能够筛选消化不良患者是否存在萎缩性胃炎。这种简单且具有成本效益的方法可以补充常规筛查 ELISA，以增加检测当前感染和萎缩性胃炎的机会。
