Centro de Investigación sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Cuernavaca, México.
Centro de Investigación en Salud Poblacional, Instituto Nacional de Salud Pública, Cuernavaca, México.
J Med Microbiol. 2013 Apr;62(Pt 4):591-598. doi: 10.1099/jmm.0.050567-0. Epub 2013 Jan 3.
Infection with Helicobacter pylori cytotoxin-associated gene A (CagA)-positive strains is associated with the development of gastric cancer (GC). However, some reports have failed to demonstrate an increased frequency of CagA antibodies in GC patients. This study evaluated the response of IgG antibody and subclasses IgG1 and IgG2 against both CagA and H. pylori membrane antigens in patients with pre-cancerous lesions and cases with GC. A total of 137 patients with a positive serum IgG response to H. pylori were selected: 46 with intestinal metaplasia, 41 with gastric adenocarcinoma and 50 with non-atrophic gastritis (NAG) considered as controls. The response of total IgG, IgG1 and IgG2 was investigated by immunoblot and ELISA using an in-house recombinant CagA and membrane antigens from a local strain, and possible associations were estimated using a logistic regression model. Compared with NAG patients, GC patients showed a higher frequency of IgG2 CagA antibodies (55.2 vs 15.4 %, P = 0.001), but a lower frequency (80.5 vs 96.0 %, P = 0.021) and diminished levels of IgG2 H. pylori antibodies [12.5 vs 21.9 ELISA units (EU), P = 0.007]. GC patients also presented lower levels of CagA (32.6 vs 42.4 EU, P = 0.004) and H. pylori total IgG (33.7 vs 38.7 EU, P = 0.029). GC was associated with a positive IgG2 CagA response [odds ratio (OR) = 3.74, 95 % confidence interval (CI) 1.81-5.37; P = 0.002] and with a low titre of total IgG CagA antibodies (OR = 2.18, 95 % CI 1.35-2.69; P = 0.006). These results suggest that the IgG2 response to CagA could be used as a novel serological marker to identify patients with H. pylori-associated GC.
幽门螺杆菌细胞毒素相关基因 A (CagA)-阳性菌株感染与胃癌 (GC) 的发展有关。然而，一些报道未能证明 CagA 抗体在 GC 患者中的频率增加。本研究评估了针对癌前病变和 GC 患者的 CagA 和幽门螺杆菌膜抗原的 IgG 抗体及其亚类 IgG1 和 IgG2 的反应。选择了 137 例血清 IgG 对幽门螺杆菌呈阳性反应的患者：46 例肠上皮化生，41 例胃腺癌和 50 例非萎缩性胃炎（NAG）作为对照。使用来自本地菌株的重组 CagA 和膜抗原通过免疫印迹和 ELISA 研究了总 IgG、IgG1 和 IgG2 的反应，并使用逻辑回归模型估计了可能的关联。与 NAG 患者相比，GC 患者 IgG2 CagA 抗体的频率更高（55.2%比 15.4%，P=0.001），但 IgG2 幽门螺杆菌抗体的频率较低（80.5%比 96.0%，P=0.021）和水平降低[12.5 比 21.9 ELISA 单位（EU），P=0.007]。GC 患者的 CagA（32.6 比 42.4 EU，P=0.004）和幽门螺杆菌总 IgG（33.7 比 38.7 EU，P=0.029）水平也较低。GC 与 IgG2 CagA 反应阳性相关[比值比（OR）=3.74，95%置信区间（CI）1.81-5.37；P=0.002]，与 CagA 总 IgG 抗体低滴度相关（OR=2.18，95%CI 1.35-2.69；P=0.006）。这些结果表明，CagA 的 IgG2 反应可作为识别与幽门螺杆菌相关 GC 的新型血清学标志物。
