Helicobacter pylori infection: is there circulating vacuolating cytotoxin A or cytotoxin-associated gene A protein?

Ichiro Imoto; Satoko Oka; Masaki Katsurahara; Misaki Nakamura; Taro Yasuma; Junko Akada; Corina N D'Alessandro-Gabazza; Masaaki Toda; Noriyuki Horiki; Esteban C Gabazza; Yoshio Yamaoka

doi:10.1186/s13099-022-00519-8

Helicobacter pylori infection: is there circulating vacuolating cytotoxin A or cytotoxin-associated gene A protein?

Gut Pathog. 2022 Dec 3;14(1):43. doi: 10.1186/s13099-022-00519-8.

Authors

Affiliations

¹ Digestive Endoscopy Center, Department of Internal Medicine, Doshinkai Tohyama Hospital, Minamishinmachi 17-22, Tsu, Mie, 514-0043, Japan.
² Department of Gastroenterology and Hepatology, Mie University Faculty and Graduate School of Medicine, Mie University Hospital, Edobashi 2-174, Tsu, Mie, 514-8507, Japan.
³ Department of Immunology, Mie University Faculty and Graduate School of Medicine, Mie University Hospital, Edobashi 2-174, Tsu, Mie, 514-8507, Japan.
⁴ Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-Machi, Yufu, Oita, 879-5593, Japan.
⁵ Department of Immunology, Mie University Faculty and Graduate School of Medicine, Mie University Hospital, Edobashi 2-174, Tsu, Mie, 514-8507, Japan. gabazza@doc.medic.mie-u.ac.jp.
⁶ Department of Medicine, Gastroenterology and Hepatology Section, Baylor College of Medicine, Houston, TX, USA.

Abstract

Background: Helicobacter pylori infection is a well-recognized cause of gastric diseases, including chronic gastritis, peptic ulcer, and gastric cancer. Vacuolating cytotoxin-A (VacA) and cytotoxin-associated gene A protein (CagA) play a role in the pathogenesis of H. pylori-related gastric diseases. Also, extragastric disorders are frequent morbid complications in patients with H. pylori infection. However, the direct pathologic implication of these virulence factors in extragastric manifestations remains unclear. Our hypothesis in the present study is that VacA and CagA released by H. pylori in the gastric mucosa leak into the systemic circulation, and therefore they can be measured in serum.

Results: Sixty-two subjects were enrolled. They were allocated into the H. pylori-positive and H. pylori-negative groups. VacA and CagA were measured by immunoassays. The serum levels of VacA and CagA above an upper limit cut-off (mean plus two standard deviations of the mean in patients without H. pylori infection) were considered positive for antigen circulating level. Five out of 25 H. pylori-positive patients were positive for both serum VacA and serum CagA. The serum levels of VacA and CagA were significantly correlated with the serum levels of anti- H. pylori antibody and interleukin-12p70 among all H. pylori-positive and H. pylori-negative patients.

Conclusions: This study suggests that spill-over of VacA and CagA antigens in the systemic circulation may occur in some patients with H. pylori infection.

Keywords: Cytokine; Cytotoxin-associated gene A (CagA); Extragastric disease; Helicobacter pylori; Systemic circulation; Vacuolating cytotoxin A (VacA).