Features of the cytokine status in patients with HP-negative chronic gastritis

Aim: to study the immunological characteristics of patients with H. pylori-unassociated chronic gastritis with its comorbidity with allergic rhinitis.

Materials and methods. The study included patients aged 18 to 40 years: 47 healthy individuals (comparison group) and 140 people, of which 66 people had chronic gastritis, 43 people had seasonal allergic rhinitis in remission, 31 people had a combination of both. Conducted a clinical examination, determination of serum concentrations of IL-4, IL-5, IL-6, IL-8, IL-10, IL-18, MCP-1, total IgE, detection of IgG to the nuclear antigen of the Epstein-Barr virus.

Results: During the study, we showed that H. pylori-non-associated chronic gastritis is characterized by a decrease in the level of monocyte-macrophage cytokines (IL-6 and IL-18, but not IL-8), but an increase in the production of Th2-dependent cytokines (IL-5 and IL-4), as well as total Ig E. In addition, H. pylori-non-associated chronic gastritis in patients without allergic rhinitis is associated with an increased frequency of detection of IgG to the nuclear antigen of the Epstein-Barr virus in blood serum (80.0% vs 48–55% of cases in other groups, p<0, 05).

Conclusion. Thus, H. pylori-non-associated chronic gastritis is a multidisciplinary problem, which, from an immunopathogenetic point of view, is characterized by a Th2-phenotype of the immune response in such patients, including in the absence of allergic pathology, which determines the need for a wider involvement of data in the examination. patients of specialists of other profiles (allergists, infectious disease specialists, etc.).

1. Ho S.W., Lin C. P., Ku M. S. Th e impact of allergic rhinitis on gastrointestinal disorders among young adults. J Eval Clin Pract. 2020; 26(1): 242-247. https://doi.org/10.1111/jep.13108

2. Kakaje A., Alhalabi M. M., Alyousbashi A., Ghareeb A. Allergic rhinitis, asthma and laryngopharyngeal refl ux disease: a cross-sectional study on their reciprocal relations. Sci Rep. 2021; 11(1): 2870. https://doi.org/10.1038/s41598-020-80793-1

3. Kung Y.M., Tsai P. Y., Chang Y. H., et al. Allergic rhinitis is a risk factor of gastro-e sophageal refl ux disease regardless of the presence of asthma. Sci Rep. 2019; 9: 15535. https://doi.org/10.1038/s41598-019-51661-4

4. Fuenmayor-Boscán A, Hernández-Rincón I, Arismendi-Morillo G. et al. Changes in the severity of gastric mucosal infl ammation associated with Helicobacter pylori in humans coinfected with intestinal helminths. Indian J Gastroenterol. 2020; 39(2): 186-195. https://doi.org/10.1007/s12664-020-01023-0

5. Matveeva L.V., Kapkaeva R. C., Chudajkin A. N., Mishanina L. S. Changes monocyte chemoattractants protein-1 in Helicobacter pylori-associated gastroduodenal diseases. Russian Journal of Infection and Immunity. 2018;8(2):150-156. (In Russ.) https://doi.org/10.15789/2220-7619- 2018-2-150-156

6. Nagata K., Nishiyama C. IL-10 in Mast Cell-M ediated Immune Responses: Anti-I nflammatory and Proinfl ammatory Roles. Int J Mol Sci. 2021; 22(9): 4972. https://doi.org/10.3390/ijms22094972

7. Daugule I., Zavoronkova J., Santare D. Helicobacter pylori and allergy: Update of research. World J Methodol. 2015; 5(4): 203-11. https://doi.org/10.5662/wjm.v5.i4.203

8. Order of the Ministry of Health and Social Development of the Russian Federation dated November 22, 2004 No. 248 «On approval of the standard of medical care forpatients with chronic gastritis, duodenitis, dyspepsia.» Available at: http://www.gastroscan.ru/literature/authors/2355 (Access: 01/18/2020)

9. Lazebnik L.B., Alexeenko S. A., Lyalukova E. A., et al. Recommendations on management of primary care patients with symptoms of dyspepsia. Experimental and Clinical Gastroenterology. 2018;(5):4-18. (In Russ.)

10. Alekseenko S.A., Bagdasaryan A. A., Bakulin I. G., et al. Brief algorithms for managing patients at the stage of providing primary health care. A guide for general practitioners. Moscow: Vidoks Publ., 2019; 20 P. (in Russ.)

11. Maev I.V., Drapkina O. M., Lazebnik L. B. Statements for an algorithm for the management of primary unexamined patients with symptoms of dyspepsia in primary health care. Profi lakticheskaya Meditsina. 2019;22(1):35- 42. (In Russ.). https://doi.org/10.17116/profmed20192201135

12. Ivashkin V.T., Mayev I. V., Lapina T. L., et al. Diagnostics and treatment of Helicobacter pylori infection in adults: Clinical guidelines of the Russian gastroenterological association. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2018;28(1):55-70. (In Russ.) https://doi.org/10.22416/1382-4376-2018-28-1-55-70

13. Ilyina N.I., Kurbacheva O. M., Pavlova K. S., Polner S. A. Federal clinical guidelines: Allergic rhinitis. Russian Journal of Allergy. 2017; 14(2): 47-54. (In Russ.) https://doi.org/10.36691/RJA323

14. Hussain Z., El-O mar E., Lee Y. Y. Dual infective burden of Helicobacter pylori and intestinal parasites: Good or bad news for the host? Indian J Gastroenterol. 2020; 39(2): 111-116. https://doi.org/10.1007/s12664-020-01045-8

15. Ageeva E. S. Effects of cytokines in the pathogenesis of Helicobacter pylori-associated chronic gastritis and peptic ulcer. Siberian Medical Journal (Irkutsk). 2014; 125(2): 5-8. (in Russ.)

16. Khaitov R.M., Ilyina N. I. [Allergology]. Moscow. GEOTAR-Media Publ., 2009, 256 p. (In Russ.)

17. Burton O.T., Darling A. R., Zhou J. S., et al. Direct effects of IL-4 on mast cells drive their intestinal expansion and increase susceptibility to anaphylaxis in a murine model of food allergy. Mucosal Immunol. 2013; 6(4): 740-50. https://doi.org/10.1038/mi.2012.112

18. Wechsler M.E., Munitz A., Ackerman S. J., et al. Eosinophils in Health and Disease: A State-of-the-A rt Review. Mayo Clin Proc. 2021; 96(10): 2694-2707. https://doi.org/10.1016/j.mayocp.2021.04.025

19. Khomeriki S. G. Laboratory diagnosis of Helicobacter pylori infection. St. Petersburg. “AMA” Publ., 2011, 110 p. (In Russ.)

20. Banerjee A., Mukhopadhyay A. K., Paul S. et al. Unveiling the intricacies of Helicobacter pylori-i nduced gastric infl ammation: T Helper cells and matrix metalloproteinases at a crossroad. Current topics in gastritis - 2012 (Croatia: InTech Publishers). 2013; 7: 113-151. Available at: https://www.intechopen.com/chapters/41558 (Access: 15.04.2020).

21. Oh D.S., DeMeester S.R., Vallbohmer D., et al. Reduction of interleukin 8 gene expression in refl ux esophagitis and Barrett’s esophagus with antirefl ux surgery. Arch Surg. 2007; 142(6): 554-559. https://doi.org/10.1001/archsurg.142.6.554

22. Iraklionova N.S., Belan E. B. Some features of general hematological parameters and production of cytokines that regulate infl ammation in allergic rhinitis. Russian Journal of Allergy. 2021; 18(3): 35-43. (In Russ.) https://doi.org/10.36691/RJA1444

23. Zavros Y., Rathinavelu S., Kao J. Y., et al. Treatment of Helicobacter gastritis with IL-4 requires somatostatin. Proc Natl Acad Sci USA. 2003; 100(22): 12944-9. https://doi.org/10.1073/pnas.2135193100

24. Velikova T. Multiple roles of IL-18 in infl ammation. J Mucosal Immunol. 2018; 2(2): 110.

25. Krulevsky V. A. Clinical and morphological features of chronic gastritis in different age groups with Epstein-Barr virus infection. Fundamental research. 2014; 7: 299-303. (In Russ.)

26. de Souza C. R.T,. Almeida M. C.A., Khayat A. S., et al. Association between Helicobacter pylori, Epstein-B arr virus, human papillomavirus and gastric adenocarcinomas. World J Gastroenterol. 2018; 24(43):4 928-4938. https://doi.org/10.3748/wjg.v24.i43.4928

27. Del Moral-Hernández O., Castañón-Sánchez C.A., Reyes-Navarrete S., et al. Multiple infections by EBV, HCMV and Helicobacter pylori are highly frequent in patients with chronic gastritis and gastric cancer from Southwest Mexico: An observational study. Medicine (Baltimore). 2019; 98(3): e14124. https://doi.org/10.1097/MD.0000000000014124

28. Zhang Y., Molot R. Severe gastritis secondary to Epstein-Barr viral infection. Unusual presentation of infectious mononucleosis and associated diff use lymphoid hyperplasia in gastric mucosa. Arch Pathol Lab Med. 2003; 127(4): 478-480. https://doi.org/10.5858/2003-127-0478-SGSTEV

29. Lutsky A.A., ZHirkov A.A., Lobzin D.YU. et. al. Interferon-γ: biological function and signifi cance for the diagnosis of cellular immune response. Journal of Infectology. 2015; 7(4): 10-22. (In Russ.) https://doi.org/10.22625/2072-6732-2015-7-4-10-22

30. Hamza T., Barnett J. B., Li B. Interleukin 12 a key immunoregulatory cytokine in infection applications. Int J Mol Sci. 2010; 11(3): 789-806. https://doi.org/10.3390/ijms11030789

31. Mikhail I., Grayson M. H. Asthma and viral infections: An intricate relationship. Ann Allergy Asthma Immunol. 2019; 123(4): 352-358. https://doi.org/10.1016/j.anai.2019.06.020

32. Akdis C. A. Does the epithelial barrier hypothesis explain the increase in allergy, autoimmunity and other chronic conditions? Nat Rev Immunol. 2021; 21(11): 739-751. https://doi.org/10.1038/s41577-021-00538-7

33. Esteve C., Resano A., Díaz-T ejeiro P., Fernández-B enítez M. Eosinophilic gastritis due to Anisakis: a case report. Allergol Immunopathol (Madr). 2000; 28(1): 21-23.

34. Wang L.J., Cao Y., Shi H. N. Helminth infections and intestinal infl ammation. World J Gastroenterol. 2008; 14(33): 5125-5132. https://doi.org/10.3748/wjg.14.5125

35. Pellefi gues C. IgE Autoreactivity in atopic aermatitis: Paving the road for autoimmune diseases? Antibodies (Basel). 2020; 9(3): 47. https://doi.org/10.3390/antib9030047