Basic Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 7, 2017; 23(1): 48-59
Published online Jan 7, 2017. doi: 10.3748/wjg.v23.i1.48
Novel CagA ELISA exhibits enhanced sensitivity of Helicobacter pylori CagA antibody
Yuichi Matsuo, Yasutoshi Kido, Junko Akada, Seiji Shiota, Tran Thanh Binh, Tran Thi Huyen Trang, Ho D Q Dung, Pham Huu Tung, Tran Dinh Tri, Ngo P Minh Thuan, Le Quang Tam, Bui Chi Nam, Vu Van Khien, Yoshio Yamaoka
Yuichi Matsuo, Yasutoshi Kido, Junko Akada, Seiji Shiota, Tran Thanh Binh, Tran Thi Huyen Trang, Yoshio Yamaoka, Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, Oita 879-5593, Japan
Seiji Shiota, Department of General Medicine, Oita University Faculty of Medicine, Yufu, Oita 879-5593, Japan
Tran Thanh Binh, Pham Huu Tung, Tran Dinh Tri, Ngo P Minh Thuan, Ho DQ Dung, Department of Endoscopy, Cho Ray Hospital, Hochiminh 800010, Vietnam
Tran Thi Huyen Trang, Department of Molecular Biology, 108 Military Central Hospital, Hanoi 100083, Vietnam
Le Quang Tam, Department of Endoscopy, Daklak Hospital, Daklak 55000, Vietnam
Bui Chi Nam, Department of Endoscopy, Lao Cai Hospital, Lao Cai 19000, Vietnam
Vu Van Khien, Department of Hepatogastroentrology, 108 Military Center Hospital, Hanoi 19000, Vietnam
Yoshio Yamaoka, Department of Medicine-Gastroenterology, Baylor College of Medicine and Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX 77030, United States
Author contributions: Matsuo Y, Kido Y, Akada J, Shiota S and Yamaoka Y conceived and designed the experiments; Matsuo Y, Kido Y, Akada J, Binh TT and Trang TTH performed the experiments; Binh TT, Dung HDQ, Tung PH, Tri TD, Thuan NPM, Tam LQ, Nam BC and Khien VV contributed to obtaining the samples; Matsuo Y, Kido Y, Akada J and Yamaoka Y contributed to analysis and interpretation; Matsuo Y, Kido Y, Akada J and Yamaoka Y drafted the manuscript.
Supported by the National Institutes of Health, No. DK62813; Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (in part), No. 25293104, No. 26640114 and No. 15H02657); the Japan Society for the Promotion of Science Institutional Program for Young Researcher Overseas Visits and the Strategic Funds for the Promotion of Science and Technology from the Japan Science and Technology Agency.
Institutional review board statement: Ethical approval was obtained from the Ethics Committees of Daklak Hospital and Lao Cai Hospital, Vietnam and the Oita University Faculty of Medicine, Japan.
Conflict-of-interest statement: No conflicts of interest exist.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Yamaoka Yoshio, MD, PhD, Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, Oita 879-5593, Japan. yyamaoka@oita-u.ac.jp
Telephone: +81-97-5865740 Fax: +81-97-5865749
Received: August 15, 2016
Peer-review started: August 16, 2016
First decision: September 20, 2016
Revised: October 3, 2016
Accepted: October 27, 2016
Article in press: October 27, 2016
Published online: January 7, 2017
Processing time: 142 Days and 18.8 Hours
Abstract
AIM

To develop a novel Helicobacter pylori (H. pylori) CagA antibody enzyme-linked immunosorbent assay (ELISA) suitable for detecting serum anti-CagA antibodies with high sensitivity.

METHODS

Recombinant East Asian-type CagA protein was purified and immobilized for ELISA. Serum samples from 217 Vietnamese individuals (110 H. pylori-infected and 107 uninfected individuals) were applied. Conventional ELISA from Western-type CagA and our East Asian-type CagA ELISA were evaluated by comparing 38 subjects with the Western-type genotype and 72 subjects with the East Asian-type cagA genotype. Histological scores of the gastric mucosa were determined using the updated Sydney System to examine the relationship with anti-CagA antibody titers.

RESULTS

Recombinant 70-100 kDa fragments were immobilized on the ELISA plate. In ROC analysis, the area under the curve of our East Asian-type CagA ELISA was comparable to that of conventional CagA ELISA. The sensitivity of the two ELISAs differed depending on the cagA genotype. The sensitivity of East Asian-type CagA ELISA was higher for subjects infected with East Asian-type cagA H. pylori (P < 0.001), and the sensitivity of the conventional CagA ELISA tended to be higher for subjects infected with Western cagA H. pylori (P = 0.056). The titer of anti-CagA antibody tended to correlate with monocyte infiltration scores (r = 0.25, P = 0.058) and was inversely correlated with H. pylori density (r = -0.26, P = 0.043).

CONCLUSION

The novel ELISA is useful to detect anti-CagA antibodies in East Asian countries, and the titer may be a marker for predicting chronic gastritis.

Keywords: Helicobacter pylori; cagA genotype; Anti-CagA antibody; Enzyme-linked immunosorbent assay; Inflammation; Gastritis

Core tip: We developed a novel East Asian-type CagA enzyme-linked immunosorbent assay (ELISA) to determine whether this method could detect CagA seropositivity with greater sensitivity in East Asian countries than the conventional anti-CagA antibody ELISA, which utilizes Western-type CagA as the antigen. Our findings revealed that conventional CagA ELISA underestimated CagA seropositivity in East Asian countries and the novel CagA ELISA could detect anti-CagA antibodies with higher sensitivity. In addition, the anti-CagA antibody titer tended to correlate with chronic inflammation in the stomach. Therefore, the titer of East Asian CagA ELISA may be a useful marker for predicting chronic inflammation in the gastric mucosa.