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Anti-CagA Immunoglobulin G Responses Correlate with Interleukin-8 Induction in Human Gastric Mucosal Biopsy Culture

机译:抗CagA免疫球蛋白G反应与白细胞介素8诱导人类胃粘膜活检培养中。

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摘要

Helicobacter pylori persists in the human stomach despite eliciting both cellular and humoral immune responses and inducing proinflammatory cytokines. To determine whether local humoral and cytokine responses are related to each other and to histologic responses, we studied 66 Japanese patients who underwent gastroscopy. Using specific enzyme-linked immunosorbent assays, we examined gastric antral mucosal-organ biopsy culture supernatants to assess interleukin-6 (IL-6) and interleukin-8 (IL-8) levels and antibody responses to H. pylori whole-cell antigens CagA, HspA, and HspB. Of the patients studied, 11 were H. pylori negative and 55 were H. pylori positive; by PCR, all strains were cagA+. As expected, compared to H. pylori-negative patients, H. pylori-positive patients had significantly higher humoral responses to all H. pylori antigens and had higher IL-8 (47.8 ± 3.5 versus 10.1 ± 4.3 ng/mg of biopsy protein; P < 0.001) and IL-6 levels (2.8 ± 0.3 versus 0.26 ± 0.2 ng/mg of protein; P < 0.001). Among the H. pylori-positive patients, supernatant anti-CagA immunoglobulin G (IgG) levels were significantly associated with H. pylori density (P < 0.005) and neutrophil infiltration (P < 0.005) scores. Anti-CagA immunoglobulin A levels were correlated with intestinal metaplasia (P < 0.05). Mononuclear cell infiltration scores were significantly associated with supernatant IL-6 levels (P < 0.005) and with IgG responses to whole-cell antigens (P < 0.05). Supernatant IL-8 levels were significantly associated with anti-CagA IgG (r = 0.75, P < 0.001). Anti-CagA responses correlated with neutrophil infiltration, intestinal metaplasia, H. pylori density, and IL-8 levels, suggesting that the absolute levels of these antibodies may be markers for gastric inflammation and premalignant changes in individual hosts.
机译:尽管引起细胞和体液免疫应答并诱导促炎细胞因子,幽门螺杆菌仍在人胃中持续存在。为了确定局部体液和细胞因子反应是否彼此相关以及与组织学反应是否相关,我们研究了66位接受胃镜检查的日本患者。使用特定的酶联免疫吸附测定,我们检查了胃窦粘膜器官活检培养上清液,以评估白细胞介素6(IL-6)和白细胞介素8(IL-8)的水平以及对幽门螺杆菌全细胞抗原CagA的抗体反应,HspA和HspB。在研究的患者中,幽门螺杆菌阴性11例,幽门螺杆菌阳性55例。通过PCR,所有菌株均为cagA + 。正如预期的那样,与幽门螺杆菌阴性患者相比,幽门螺杆菌阳性患者对所有幽门螺杆菌抗原的体液应答明显更高,并且IL-8更高(活检蛋白的活检蛋白分别为47.8±3.5和10.1±4.3 ng / mg; mg / mg)。 P <0.001)和IL-6水平(2.8±0.3对0.26±0.2 ng / mg蛋白质; P <0.001)。在幽门螺杆菌阳性患者中,上清液中的抗CagA免疫球蛋白G(IgG)水平与幽门螺杆菌密度(P <0.005)和中性粒细胞浸润(P <0.005)得分显着相关。抗CagA免疫球蛋白A水平与肠上皮化生相关(P <0.05)。单核细胞浸润评分与上清液IL-6水平(P <0.005)和IgG对全细胞抗原的反应( P <0.05)显着相关。上清液IL-8水平与抗CagA IgG显着相关( r = 0.75, P <0.001)。抗CagA反应与中性粒细胞浸润,肠上皮化生, H相关。幽门螺杆菌密度和IL-8水平,提示这些抗体的绝对水平可能是个体宿主胃部炎症和癌前变化的标志。

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