IgG2 response and low IgG titre specific to Helicobacter pylori CagA as serological markers for gastric cancer

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 To 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.