Identification of markers for the major pathogenicity factors of Helicobacter pylori
- Authors: Belaia O.F.1, Gutkin D.S.2, Vakhrameeva M.S.3, Paevskaya O.A.1, Sundukova A.N.2, Shantseva A.S.1, Volchkova E.V.1
-
Affiliations:
- Sechenov First Moscow State Medical University
- Penza Hospital N.N. Burdenko
- National Research Center for Epidemiology and Microbiology named after N.F. Gamaleya
- Issue: Vol 30, No 3 (2025)
- Pages: 149-156
- Section: Original study articles
- URL: https://ogarev-online.ru/1560-9529/article/view/373788
- DOI: https://doi.org/10.17816/EID678362
- EDN: https://elibrary.ru/UQRNJV
- ID: 373788
Cite item
Abstract
BACKGROUND: Identification of Helicobacter pylori pathogenicity factors is crucial for improving diagnosis and understanding the pathogenesis of associated diseases.
AIM: The study aimed to establish the detection rates of markers associated with major H. pylori pathogenic factors in patients with chronic gastritis and peptic ulcer.
METHODS: The study included 67 patients with chronic gastritis and 57 patients with peptic ulcer. All participants underwent a fibroesophagogastroduodenoscopy with a rapid urease test (AMA LLC, Russia), followed by a histological examination for H. pylori. The following were also tested: stool filtrates for H. pylori antigen using an immunochromatographic assay (H. pylori test, Novamed Ltd., Israel); serum for anti-CagA antibodies via enzyme-linked immunosorbent assay (Anti-Helicobacter pylori CagA ELISA, ECOlab JSC, Russia); and fecal and salivary samples for O antigen (LPS), VacA, and CagA antigens using a coagglutination test (Gamaleya National Research Center for Epidemiology and Microbiology, Russia).
RESULTS: Positive rapid urease test results were obtained in 61.9% of patients. Serum CagA antibodies were detected in 51% of patients, and H. pylori antigen was detected in the feces of 27.9% of patients (p ≥ 0.05). The coagglutination test demonstrated the highest diagnostic performance: O antigen, VacA, and CagA antigens were detected in the fecal and/or salivary samples of 83.1% of patients at a diagnostic titer threshold of ≥1:8, which was significantly higher than that achieved by other tests. The rate of CagA antibody detection in serum was twice as high with a positive rapid urease test result. Esophagogastroduodenoscopy and rapid urease testing revealed H. pylori in 40.3% (27) of patients with chronic gastritis and in 56.1% (31) of patients with peptic ulcers. The coagglutination test detected VacA and/or CagA antigens in 90.6% of stool filtrate samples and 88.5% of salivary samples. Both antigens simultaneously were detected in 67.5% and 65.1% of the fecal and salivary samples, respectively. The rate of simultaneous detection of VacA and CagA antigens in feces was significantly higher in patients with peptic ulcers and positive rapid urease test results compared with other subgroups. There was no significant difference in the rate of simultaneous detection of these antigens in saliva across patient subgroups.
CONCLUSION: The primary advantage of the coagglutination test is the non-invasive, simultaneous detection of three key, synergistic H. pylori pathogenicicty factors in feces and/or saliva: O antigen (a marker of replication), VacA antigen (vacuolating cytotoxin), and CagA antigen (a pathogenicity island marker and Class I bacterial co-oncogene) The study confirmed that saliva can be used to detect H. pylori in children and older patients, when invasive testing is not an option.
About the authors
Olga F. Belaia
Sechenov First Moscow State Medical University
Author for correspondence.
Email: ofbelaya@mail.ru
ORCID iD: 0000-0002-2722-1335
SPIN-code: 3921-7227
MD, Dr. Sci. (Medicine), Professor
Russian Federation, MoscowDenis S. Gutkin
Penza Hospital N.N. Burdenko
Email: daniilgutkin@mail.ru
ORCID iD: 0000-0003-2025-2929
SPIN-code: 2711-5397
MD
Russian Federation, PenzaMaria S. Vakhrameeva
National Research Center for Epidemiology and Microbiology named after N.F. Gamaleya
Email: vrhbnm@rambler.ru
ORCID iD: 0000-0001-9057-5542
SPIN-code: 4673-6974
MD, Cand. Sci. (Medicine)
Russian Federation, MoscowOlga A. Paevskaya
Sechenov First Moscow State Medical University
Email: paevskajao@rambler.ru
ORCID iD: 0000-0003-4917-3992
SPIN-code: 7410-3130
MD, Cand. Sci. (Medicine)
Russian Federation, MoscowAnna N. Sundukova
Penza Hospital N.N. Burdenko
Email: bur39pnz@mail.ru
ORCID iD: 0000-0001-7360-3791
SPIN-code: 8238-2758
MD, Cand. Sci. (Medicine)
Russian Federation, PenzaAnastasiia S. Shantseva
Sechenov First Moscow State Medical University
Email: an.shants@yandex.ru
ORCID iD: 0009-0005-3391-9843
SPIN-code: 4180-6881
MD
Russian Federation, MoscowElena V. Volchkova
Sechenov First Moscow State Medical University
Email: antononina@rambler.ru
ORCID iD: 0000-0003-4581-4510
SPIN-code: 3342-4681
MD, Dr. Sci. (Medicine), Professor
Russian Federation, MoscowReferences
- Atiq A, Hashim M, Khan FW, et al. Morphological spectrum of gastritis in endoscopic biopsies and its association with Helicobacter pylori infection. Cureus. 2023;15(8):e43084. doi: 10.7759/cureus.43084 EDN: RQPRBE
- Hooi JKY, Lai WY, Ng WK, et al. Global prevalence of Helicobacter pylori infection: Systematic review and meta-analysis. Gastroenterology. 2017;153(2):420–429. doi: 10.1053/j.gastro.2017.04.022 EDN: YGUITD
- Malfertheiner P, Megraud F, O’Morain CA, et al. Management of Helicobacter pylori infection: the Maastricht V/Florence consensus report. Gut. 2017;66(1):6–30. doi: 10.1136/gutjnl-2016-312288 EDN: CIGHNB
- Marshall B, Warren JR. Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet. 1984;323(890):1311-1315. doi: 10.1016/s0140-6736(84)91816-6
- Peek RM, Blaser MJ. Helicobacter pylori and gastrointestinal tract adenocarcinomas. Nat Rev Cancer. 2002;2(1):28–37. doi: 10.1038/nrc703
- Elbehiry A, Marzouk E, Aldubaib M, et al. Helicobacter pylori infection: current status and future prospects on diagnostic, therapeutic and control challenges. Antibiotics (Basel). 2023;12(2):191. doi: 10.3390/antibiotics12020191 EDN: INWFHI
- Engelsberger V, Gerhard M, Mejías-Luque R. Effects of Helicobacter pylori infection on intestinal microbiota, immunity and colorectal cancer risk. Front Cell Infect Microbiol. 2024;14:1339750. doi: 10.3389/fcimb.2024.1339750 EDN: LHIOTY
- Dore MP, Pes GM. Trained immunity and trained tolerance: The case of Helicobacter pylori infection. Int J Mol Sci. 2024;25(11):5856. doi: 10.3390/ijms25115856 EDN: TSLVJI
- Zhang X, Arnold IC, Müller A. Mechanisms of persistence, innate immune activation and immunomodulation by the gastric pathogen Helicobacter pylori. Curr Opin Microbiol. 2020;54:1–10. doi: 10.1016/j.mib.2020.01.003 EDN: IVMDOJ
- Rostami SFA, Khaledi M, Dalilian F, et al. Vacuolating cytotoxin A (VacA) and extracellular vesicles in Helicobacter pylori: Two key arms in disease development. Iran J Pathol. 2025;20(1):1–17. doi: 10.30699/ijp.2024.2031417.3312 EDN: UPBRKS
- Taylor JM, Ziman ME, Huff JL, et al. Helicobacter pylori lipopolysaccharide promotes a Th1 type immune response in immunized mice. Vaccine. 2006;24(23):4987–4994. doi: 10.1016/j.vaccine.2006.03.043
- Bodger K, Bromelow K, Wyatt JI, Heatley RV. Interleukin 10 in Helicobacter pylori associated gastritis: Immunohistochemical localisation and in vitro effects on cytokine secretion. J Clin Pathol. 2001;54(4):285–292. doi: 10.1136/jcp.54.4.285
- Frauenlob T, Neuper T, Mehinagic M, et al. Helicobacter pylori infection of primary human monocytes boosts subsequent immune responses to LPS. Front Immunol. 2022;13:847958. doi: 10.3389/fimmu.2022.847958 EDN: VKLQHM
- Hauke M, Metz F, Rapp J, et al. Helicobacter pylori modulates heptose metabolite biosynthesis and heptose-dependent innate immune host cell activation by multiple mechanisms. Microbiol Spectr. 2023;11(3):e0313222. doi: 10.1128/spectrum.03132-22 EDN: BLTIFE
- Coletta S, Battaggia G, Della Bella C, et al. ADP-heptose enables Helicobacter pylori to exploit macrophages as a survival niche by suppressing antigen-presenting HLA-II expression. FEBS Lett. 2021;595(16):2160–2168. doi: 10.1002/1873-3468.14156 EDN: ZCVVEL
- Patent RUS №1182400 A1/ 30.09.1985. Belaya YuA, Prozorovsky SV, Bystrova SM, Belaya OF, Petrukhin VG. Method for performing a coagglutination reaction. Available from: https://patents.su/3-1182400-sposob-postanovki-reakcii-koagglyutinacii.html (In Russ.)
- Patent RUS №2186394/ 31.01.2000. Belaja JuA, Belaja OF, Petrukhin VG. Method of preparing diagnosticum for detection of Helicobacter pylori antigen in coagglutination reaction. Available from: https://allpatents.ru/patent/2186394.html (In Russ.) EDN: XPWALH
- Bely YuF, Sheklakova LA, Vakhrameeva MS, et al. Production of recombinant fragment of VacA protein and development of non-invasive method for the diagnosis of Helicobacter pylori infection. Molecular Genetics, Microbiology and Virology. 2005;1:32–35. EDN: HSGFNF
- Patent RUS №2232989/ 20.07.2004. Belaja JuA, Vakhrameeva MS, Belyj JuF, Belaja OF, Petrukhin VG. Method for preparing test-system for determination of Helicobacter pylori cytotoxin-associated protein antigens in biological material in infected patients by co-agglutination reaction. Available from: https://patents.google.com/patent/RU2232989C1/ru (In Russ.). EDN: ZNZWIX
- Reshetnyak VI, Burmistrov AI, Sabirov DJM. H. Pylori: is everything so obvious? The bulletin of emergency medicine. 2022;15(5):79–86. doi: 10.54185/tbem/vol15_iss5/a14 EDN: CRJNXS
Supplementary files
