Роль Helicobacter pylori в патогенезе некоторых гематологических заболеваний

Helicobacter pylori считается одной из значимых причин формирования патологии желудочно-кишечного тракта. Данные о роли хеликобактериоза в развитии внежелудочных заболеваний подтверждаются положительным эффектом эрадикационной терапии, в частности, на нормализацию картины периферической крови. Несмотря на это, многие аспекты остаются нераскрытыми. Однако несомненно, что Н. pylori при своей персистенции на желудочном эпителии создает условия для хронизации местного и системного воспаления. Целью обзора явился анализ литературных данных о роли бактериальных факторов Н. pylori в развитии железо- и В12-дефицитной анемии, а также тромбоцитопенической пурпуры, включенных Международным консенсусом в круг показаний для диагностики и лечения хеликобактерной инфекции. Материал и методы. Поиск источников литературы осуществлен с помощью баз данных PubMed, CyberLeninka, eLibrary, Google Scholar. Результаты. Работами последних лет показано вовлечение многих факторов патогенности Н. pylori в развитие анемии и тромбоцитопенической пурпуры через формирование эрозивно-язвенных поражений слизистой оболочки, гипоацидности, хронического системного воспаления и аутоиммунного ответа. Данные о связи этих изменений с гематологическими синдромами, как и о самостоятельном влиянии эрадикации на нормализацию лабораторных показателей крови, противоречивы. Не находит подтверждения теория конкуренции Н. pylori как симбионта за усвоение железа хозяина. Заключение. Представляются необходимыми дальнейшие исследования по взаимосвязи Н. pylori и заболеваний крови. Перспективно изучение и применение диетологических подходов к сохранению целостности слизевого барьера и предотвращению бактериальной адгезии.

1. Ивашкин В.Т., Маев И.В., Лапина Т.Л., Шептулин А.А., Трухманов А.С., Баранская Е.К., Абдулхаков Р.А., Алексеева О.П., Алексеенко С.А., Дехнич Н.Н., … Цуканов В.В. Клинические рекомендации Российской гастроэнтерологической ассоциации по диагностике и лечению инфекции Helicobacter pylori у взрослых. Рос. ж. гастроэнтерол., гепатол., колопроктол. 2018;28(1):55-70. https://doi.org/10.22416/1382-4376-2018-28-1-55-70

2. Смирнова О.В., Синяков А.А. Влияние Helicobacter pylori на особенности цитокиновой регуляции при хроническом атрофическом гастрите. Инфекц. и иммунитет. 2020;10(1):187-192. https://doi.org/10.15789/2220-7619-IOH-1167

3. Öztekin M., Yılmaz B., Agagündüz D., Capasso R. Overview of Helicobacter pylori infection: clinical features, treatment and nutritional aspects. Diseases. 2021;9(4):66. https://doi.org/10.3390/diseases9040066

4. Chmiela M., Gonciarz W. Molecular mimicry in Helicobacter pylori infections. World J. Gastroenterol. 2017;23(22):3964-3977. https://doi.org/10.3748/wjg.v23. i22.3964

5. Campuzano-Maya G. Hematologic manifestations of Helicobacter pylori infection. World J. Gastroenterol. 2014;20(36):12818-12838. https://doi.org/10.3748/wjg. v20.i36.12818

6. Mladenova I. Clinical relevance of Helicobacter pylori infection. J. Clin. Med. 2021;10:3473. https://doi.org/10.3390/jcm10163473

7. Malfertheiner P., Megraud F., O’Morain C.A., Gisbert J.P., Kuipers E.J., Axon A.T., Bazzoli F., Gasbarrini A., Atherton J., Graham D.Y., ... European Helicobacter and Microbiota Study Group and Consensus panel. Management of Helicobacter pylori infection - the Maastricht V/ Florence Consensus Report. Gut. 2017;66:6-30. https://doi.org/10.1136/gutjnl-2016-312288

8. Chey W.D., Leontiadis G.I., Howden C.W., Moss S.F. ACG Clinical Guideline: treatment of Helicobacter pylori infection. Am. J. Gastroenterol. 2017;112(2):212-239. https://doi.org/10.1038/ajg.2016.563

9. Tsay F.W., Hsu P.I. H. pylori infection and extra-gastroduodenal diseases. J. Biomed. Sci. 2018;25(1):65. https://doi.org/10.1186/s12929-018-0469-6

10. Tseng D.S., Li D., Cholleti S.M., Wei J.C., Jodesty Y., Pham H.V. Effect of Helicobacter pylori treatment on unexplained iron deficiency anemia. Perm. J. 2019;23:18-195. https://doi.org/10.7812/TPP/18-195

11. Stasi R., Sarpatwari A., Segal J.B., Osborn J., Evangelista M.L., Cooper N., Provan D., Newland A., Amadori S., Bussel J.B. Effects of eradication of Helicobacter pylori infection in patients with immune thrombocytopenic purpura: a systematic review. Blood. 2009;113:1231-1240. https://doi.org/10.1182/ blood-2008-07-167155

12. Blecker U., Renders F., Lanciers S., Vandenplas Y. Syncopes leading to the diagnosis of a Helicobacter pylori positive chronic active haemorrhagic gastritis. Eur. J. Pediatr. 1991;150(8):560-561. https://doi.org/10.1007/BF02072207

13. Rodriguez-Castro K.I., Franceschi M., Noto A., Miraglia C., Nouvenne A., Leandro G., Meschi T., de’ Angelis G.L., di Mario F. Clinical manifestations of chronic atrophic gastritis. Acta Biomed. 2018;89(8):88- 92. https://doi.org/10.23750/abm.v89i8-S.7921

14. Emiralioglu N., Yenicesu I., Sari S., Egritas O., Poyraz A., Pasaoglu O.T., Celik B., Dalgic B. An insight into the relationships between prohepcidin, iron deficiency anemia, and interleukin-6 values in pediatric Helicobacter pylori gastritis. Eur. J. Pediatr. 2015;174(7):903-910. https://doi.org/10.1007/s00431-014-2482-4

15. Haile K., Yemane T., Tesfaye G., Wolde D., Timerga A., Haile A. Anemia and its association with Helicobacter pylori infection among adult dyspeptic patients attending Wachemo University Nigist Eleni Mohammad Memorial Referral Hospital, Southwest Ethiopia: A cross-sectional study. PLoS One. 2021;16(1):e0245168. https://doi.org/10.1371/journal. pone.0245168

16. Xu M.Y., Cao B., Yuan B.S., Yin J., Liu L., Lu Q.B. Association of anaemia with Helicobacter pylori infection: a retrospective study. Scientific Reports. 2017;7:13434. https://doi.org/10.1038/s41598-017-13955-3

17. Hou B., Zhang M., Liu M., Dai W., Lin Y., Li Y., Gong M., Wang G. Association of active Helicobacter pylori infection and anemia in elderly males. BMC Infectious Diseases. 2019;19:228. https://doi.org/10.1186/s12879019-3849-y

18. Franceschi F., Giupponi B., Ražuka-Ebela D. Helicobacter pylori and extragastric diseases. Helicobacter. 2018;23(1):e12520. https://doi.org/10.1111/hel.12520

19. Hudak L., Jaraisy A., Haj S., Muhsen K. An updated systematic review and meta-analysis on the association between Helicobacter pylori infection and iron deficiency anemia. Helicobacter. 2017;22(1). https://doi.org/10.1111/ hel.12330

20. Tan H.J., Goh K.L. Extragastrointestinal manifestations of Helicobacter pylori infection: facts or myth? A critical review. J. Dig. Dis. 2012;13:342-349. https://doi.org/10.1111/j.1751-2980.2012.00599.x

21. Lee S.Y. Endoscopic gastritis, serum pepsinogen assay, and Helicobacter pylori infection. Korean J. Intern. Med. 2016;31:835-844. https://doi.org/10.3904/ kjim.2016.166

22. Афанасенкова Т.Е., Голованова Е.Д., Дубская Е.E. Хронический Helicobacter pylori-индуцированный гастрит с эрозивным поражением слизистой оболочки желудка у пожилых. Эксперим. и клин. гастроэнтерол. 2019;(10):33-38. https://doi.org/10.31146/1682-8658-ecg-170-10-33-38

23. Betesh A.L., Santa Ana C.A., Cole J.A., Fordtran J.S. Is achlorhydria a cause of iron deficiency anemia? Am. J. Clin. Nutr. 2015;102:9-19. doi. org/10.3945/ajcn.114.097394

24. Gravina A.G., Zagari R.M., de Musis C., Romano L., Loguercio C., Romano M. Helicobacter pylori and extragastric diseases: A review. World J. Gastroenterol. 2018;24(29):3204-3221. doi. org/10.3748/wjg. v24. i29.3204

25. Boyanova L. Role of Helicobacter pylori virulence factors for iron acquisition from gastric epithelial cells of the host and impact on bacterial colonization. Future Microbiol. 2011;6(8):843-846. https://doi.org/10.2217/ fmb.11.75

26. Šterbenc A., Jarc E., Poljak M., Homan M. Helicobacter pylori virulence genes. World J. Gastroenterol. 2019;25(33):4870-4884. https://doi.org/10.3748/wjg.v25. i33.4870

27. Scott C., Arora G., Dickson K., Lehmann C. Iron chelation in local infection. Molecules. 2021;26:189. https://doi.org/doi.org/10.3390/ molecules26010189

28. Toyokuni S., Yanatori I., Kong Y., Zheng H., Motooka Y., Jiang L. Ferroptosis at the crossroads of infection, aging and cancer. Cancer Science. 2020;111:2665-2671. https://doi.org/10.1111/cas.14496

29. Hamedi A.D., Farivar T.N., Rahmani B., Hajmanoochehri F., Razavi A.N., Jahanbin B., Dodaran M.S., Peymani A. The role of transferrin receptor in the Helicobacter pylori pathogenesis; L-ferritin as a novel marker for intestinal metaplasia. Microb. Pathog. 2019;126:157-164. https://doi.org/10.1016/j.micpath.2018.10.039

30. Chmiela M., Kupcinskas J. Review: Pathogenesis of Helicobacter pylori infection. Helicobacter. 2019;24(1):e12638. https://doi.org/10.1111/hel.12638

31. Worst D.J., Otto B.R., de Graaff J. Iron-repressible outer membrane proteins of Helicobacter pylori involved in heme uptake. Infect. Immun. 1995;63(10):4161-4165. https://doi.org/10.1128/iai.63.10.41614165.1995

32. Исаева Г.Ш., Валиева Р.И. Биологические свойства и вирулентность Helicobacter pylori. Клин. микробиол. и антимикроб. химиотерапия. 2018;20(1):14-23. https://doi.org/10.36488/cmac.2018.1.14-23

33. Olvera-Rosales L.B., Cruz-Guerrero A.E., Ramírez-Moreno E., Quintero-Lira A., ContrerasLópez E., Jaimez-Ordaz J., Castañeda-Ovando A., Añorve-Morga J., Calderón-Ramos Z.-G., Arias-Rico J. Impact of the gut microbiota balance on the health-disease relationship: the importance of consuming probiotics and prebiotics. Foods. 2021;10:1261. https://doi.org/10.3390/ foods10061261

34. Yang J., Zhou X., Liu X., Ling Z., Ji F. Role of the gastric microbiome in gastric cancer: from carcinogenesis to treatment. Front. Microbiol. 2021;12:641322. https://doi.org/10.3389/fmicb.2021.641322

35. Muhsen K., Cohen D. Helicobacter pylori infection and iron stores: a systemic review and metaanalysis. Helicobacter. 2008;13:323-340. https://doi.org/10.1111/ j.1523-5378.2008.00617.x

36. Andrews S.C., Robinson A.K., RodriguezQuinones F. Bacterial iron homeostasis. FEMS Microbio-logy Rev. 2003;27:215-237. https://doi.org/10.1016/S01686445(03)00055-X

37. Briana R., Wilson L., Bogdan A.R., Miyazawa M., Hashimoto K., Tsuji Y. Siderophores in iron metabolism: from mechanism to therapy potential. Trends Mol. Med. 2016;22(12):1077-1090. https://doi.org/10.1016/j.molmed.2016.10.005

38. Kramer J., Özkaya Ö., Kümmerli R. Bacterial siderophores in community and host interactions. Nat. Rev. Microbiol. 2020;18(3):152-163. https://doi.org/10.1038/ s41579-019-0284-4

39. Поздеев О.К., Поздеева А.О., Валеева Ю.В., Гуляев П.Е., Савинова А.Н. Механизмы взаимодействия Hеlicobacter pylori с эпителием слизистой оболочки желудка. I. Факторы патогенности, способствующие успешной колонизации. Инфекц. и иммунитет. 2018;8(3):273- 283. https://doi.org/10.15789/2220-7619-2019-2-253-261

40. Johnstonea T.C., Nolan E.M. Beyond iron: nonclassical biological functions of bacterial siderophores. Dalton Trans. 2015;44(14):6320-6339. https://doi.org/10.1039/c4dt03559c

41. Qi B., Han M. Microbial siderophore enterobactin promotes mitochondrial iron uptake and development of the host via interaction with ATP synthase. Cell. 2018;175(2):571-582. https://doi.org/10.1016/j.cell.2018.07.032

42. Yokota S., Toita N., Yamamoto S., Fujii N., Konno M. Positive relationship between a polymorphism in Helicobacter pylori neutrophil-activating protein a gene and iron-deficiency anemia. Helicobacter. 2013;18:112-116. https://doi.org/10.1111/hel.12011

43. Pich O.Q., Merrell D.S. The ferric uptake regulator of Helicobacter pylori: a critical player in the battle for iron and colonization of the stomach. Future Microbiol. 2013;8(6):725-738. https://doi.org/10.2217/fmb.13.43

44. Flores S.E., Aitchison A., Day A.S., Keenan J.I. Helicobacter pylori infection perturbs iron homeostasis in gastric epithelial cells. PLoS One. 2017;12(9):e0184026. https://doi.org/10.1371/journal. pone.0184026

45. Ellermann M., Arthur J.C. Siderophore-mediated iron acquisition and modulation of host-bacterial interactions. Free Radic. Biol. Med. 2017;105:68-78. https://doi.org/10.1016/j.freeradbiomed.2016.10.489

46. Nairz M., Weiss G. Iron in infection and immunity. Mol. Aspects Med. 2020;75:100864. https://doi.org/10.1016/j. mam.2020.100864

47. Weiss G., Ganz T., Goodnough L.T. Anemia of inflammation. Blood. 2019;33(1): 40-50. https://doi.org/10.1182/ blood-2018-06-856500

48. Pasini E., Corsetti G., Romano C., Aquilani R., Scarabelli T., Chen-Scarabelli C., Dioguardi F.S. Management of anaemia of chronic disease: beyond irononly supplementation. Nutrients. 2021;13:237. https://doi.org/10.3390/nu 13010237

49. Madu A.J., Ughasoro M.D. Anaemia of chronic disease: an in-depth review. Med. Princ. Pract. 2017;26:1-9. https://doi.org/10.1159/000452104

50. Jeyamani L., Jayarajan J., Leelakrishnan V., Swaminathan M. CagA and VacA genes of Helicobacter pylori and their clinical relevance. Indian J. Pathol. Microbiol. 2018;61(1):66-69. https://doi.org/10.4103/IJPM. IJPM_234_17

51. Yang J.Y., Kim P., Jeong S.-H., Lee S.W., Myung Y.S., Baeg M.K., Kim J.B. The effects of sulglycotide on the adhesion and the inflammation of Helicobacter pylori. Int. J. Environ. Res. Public Health. 2020;17:2918. https://doi.org/10.3390/ijerph17082918

52. Hessey S.J., Spencer J., Wyatt J.I., Sobata G., Rathbone B.J., Axon A.T., Dixon M.F. Bacterial adhesion and disease activity in Helicobacter associated chronic gastritis. Gut. 1990;31:134-138. https://doi.org/10.1136/gut.31.2.134

53. Guruge J.L., Falk P.G., Lorenz R.G., Dans M., Wirth H.P., Blaser M.J., Berg D.E., Gordon J.I. Epithelial attachment alters the outcome of Helicobacter pylori infection. Proc. Nat. Acad. Sci. USA. 1998;95(7):3925-3930. https://doi.org/10.1073/pnas.95.7.3925

54. Matsuo Y., Kido Y., Yamaoka Y. Helicobacter pylori outer membrane protein-related pathogenesis. Toxins (Basel). 2017;9:101. https://doi.org/10.3390/toxins9030101

55. Kato S., Osaki T., Kamiya S., Zhang X.S., Blaser M.J. Helicobacter pylori sabA gene is associated with iron deficiency anemia in childhood and adolescence. PLoS One. 2017;12:e0184046. https://doi.org/10.1371/journal.pone.0184046

56. Andersen L.P. Colonization and infection by Helicobacter pylori in humans. Helicobacter. 2007;12(2):12-15. https://doi.org/10.1111/j.15235378.2007.00574.x

57. Cover T.L. Helicobacter pylori diversity and gastric cancer risk. mBio. 2016;7(1):e01869-15. https://doi.org/10.1128/mBio.01869-15

58. Щербаков И.Т., Леонтьева Н.И., Филиппов В.С., Грачева Н.М., Соловьева А.И., Виноградов Н.А. Морфология воспаления слизистой оболочки желудка и двенадцатиперстной кишки с контаминацией Helicobacter pylori. Морфол. ведомости. 2019;27(3):39-45. https://doi.org/10.20340/mvmn.19(27).03.39-45

59. Пегашева И.Л., Павлович И.М., Гордиенко А.В., Чирский В.С., Ерохина А.А., Сварваль А.В. Влияние факторов патогенности Helicobacter pylori (Cag A и Vac A) на предраковые изменения слизистой оболочки желудка у больных хроническим гастритом. Эксперим. и клин. гастроэнтерол. 2019;(5):67-71. https://doi.org/10.31146/1682-8658-ecg-165-567-71

60. Vernigorodskiy S.V., Sukhan D.S. The role of the CagA gene in the occurrence of the inflammatory response of the gastric mucosa in patients with chronic Helicobacter pylori-associated gastritis. Reports of Morphology. 2018;24(3):11-18. https://doi.org/10.31393/morphology-journal-2018-24(3)-02

61. Lahner E., Carabotti M., Annibale B. Treatment of Helicobacter pylori infection in atrophic gastritis. World J. Gastroenterol. 2018;24(22):2373-2380. https://doi.org/10.3748/wjg.v24.i22.2373

62. Новиков В.В., Лапин В.А., Мелентьев Д.А., Мохонова Е.В. Особенности иммунного ответа человека на инфицирование Helicobacter pylori. МедиАль. 2019;(2):55-69. https://doi.org/10.21145/2225-00262019-2-55-69

63. Jackson S., Beck P.L., Pineo G.F., Poon M.C. Helicobacter pylori eradication: novel therapy for immune thrombocytopenic purpura? A review of the literature. Am. J. Hematol. 2005;78(2):142-150. https://doi.org/10.1002/ajh.20250

64. Asahi M., Azuma T., Ito S., Ito Y., Suto H., Nagai Y., Tsubokawa M., Tohyama Y., Maeda S., Omata M., Suzuki T., Sasakawa C. Helicobacter pylori CagA protein can be tyrosine phosphorylated in gastric epithelial cells. J. Exp. Med. 2000;191:593-602. https://doi.org/10.1084/ jem.191.4.593

65. Tummuru M.K., Sharma S.A., Blaser M.J. Helicobacter pylori picB, a homologue of the Bordetella pertussis toxin secretion protein, is required for induction of IL-8 in gastric epithelial cells. Mol. Microbiol. 1995;18:867- 876. https://doi.org/10.1111/j.1365-2958.1995.18050867.x

66. Negovan A., Iancu M., Fülöp E., Bănescu C. Helicobacter pylori and cytokine gene variants as predictors of premalignant gastric lesions. World J. Gastroenterol. 2019;25(30):4105-4124. https://doi.org/10.3748/wjg. v25.i30.4105

67. Mendoza E., Duque X., Franco J.I.F., Maldonado E.R., Morán S., Martínez G., Rodríguez A.R., Martínez H. Association between active H. pylori infection and iron deficiency assessed by serum hepcidin levels in school-age children. Nutrients. 2019;11:2141. https://doi.org/10.3390/nu11092141

68. O’Connor H.J., Axon A.T., Dixon M.F. Campylobacter-like organisms unusual in type A (pernicious anaemia) gastritis. Lancet. 1984;2:1091. https://doi.org/10.1016/ s0140-6736(84)91523-x

69. Saito M., Mori A., Irie T., Tanaka M., Morioka M. Helicobacter pylori infection is not associated with pernicious anemia in Japan. Rinsho Ketsueki. 2008;49(11):1569-1571. [In Japanese].

70. Kokkola A., Kosunen T.U., Puolakkainen P., Sipponen P., Harkonen M., Laxen F., Virtamo J., Haapiainen R., Rautelin H. Spontaneous disappearance of Helicobacter pylori antibodies in patients with advanced atrophic corpus gastritis. APMIS Journal of Pathology, Microbiology and Immulogy. 2003;111:619- 624. https://doi.org/10.1034/j.1600-0463.2003.1110604.x

71. Rodriguez A.M., Urrea D.A., Prada C.F. Helicobacter pylori virulence factors: relationship between genetic variability and phylogeographic origin. PeerJ. 2021;9:e12272. https://doi.org/10.7717/peerj.12272

72. Buerkli S., Ndiaye N.F., Cercamondi C.I., Herter-Aeberli I., Moretti D., Zimmermann M.B. Asymptomatic Helicobacter pylori infection in preschool children and young women does not predict iron bioavailability from iron-fortified foods. Nutrients. 2019;11:2093. https://doi.org/10.3390/nu11092093

73. Youssefi M., Tafaghodi M., Farsiani H., Ghazvini K., Keikha M. Helicobacter pylori infection and autoimmune diseases. Is there an association with systemic lupus erythematosus, rheumatoid arthritis, autoimmune atrophy gastritis and autoimmune pancreatitis? A systematic review and meta-analysis study. J. Microbiol. Immunol. Infect. 2021;54(3):359-369. https://doi.org/10.1016/j. jmii.2020.08.011

74. Lenti M.V., Rugge M., Lahner E., Miceli E., Toh B.-H., Genta R.M., de Block C., Hershko C., di Sabatino F. Autoimmune gastritis. Nature Reviews Disease Primers. 2020;6(1):56. https://doi.org/10.1038/ s41572-0200187-8

75. Johnson K.S., Ottemann K.M. Colonization, localization, and inflammation: the roles of H. pylori chemotaxis in vivo. Curr. Opin. Microbiol. 2018;41:51- 57. https://doi.org/10.1016/j.mib.2017.11.019

76. Sung J.J.Y., Coker O.O., Chu E., Szeto C.H., Luk S. T., Lau H.C.H., Yu J. Gastric microbes associated with gastric inflammation, atrophy and intestinal metaplasia 1 year after Helicobacter pylori eradication. Gut. 2020; 69:1572-1581. https://doi.org/10.1136/gutjnl-2019-319826

77. Колмогорова Т.О., Анчикова Т.А. Роль Нelicobacter pylori в развитии синдрома избыточного бактериального роста. Доказат. гастроэнтерол. 2019;8(3):12-18. https://doi.org/10.17116/dokgastro2019803112

78. Ливзан М.А., Гаус О.В., Мозговой С.И. Хронический атрофический гастрит: тактика курации пациента. РМЖ. Мед. обоз. 2021;5(6):427- 432. https://doi.org/10.32364/2587-6821-2021-5-6-427-432

79. Crafa P., Russo M., Miraglia C., Barchi A., Moccia F., Nouvenne A., Leandro G., Meschi T., De’Angelis G.L., Di Mario F. From Sidney to OLGA: an overview of atrophic gastritis. Acta Biomed. 2018;89(8):93-99. https://doi.org/10.23750/abm.v89i8-S.7946

80. Lahner E., Marzinotto I., Lampasona V., Dottori L., Bazzigaluppi E., Brigatti C., Secchi M., Piemonti L., Conti L., Pilozzi E., … Annibale B. Autoantibodies toward ATP4A and ATP4B subunits of gastric proton pump H1,K1-ATPase are reliable serological pre-endoscopic markers of corpus atrophic gastritis. Clinical and Translational Gastroenterology. 2020;11(10):e00240. https://doi.org/10.14309/ctg.0000000000000240

81. Rustgi S.D., Bijlani P., Shah S.C. Autoimmune gastritis, with or without pernicious anemia: epidemiology, risk factors, and clinical management. Ther. Adv. Gastroenterol. 2021;14:17562848211038771. https://doi.org/10.1177/17562848211038771

82. Franceschi F., Annalisa T., Teresa D.T., Giovanna A., Ianiro G., Franco S., Viviana G., Valentina T., Riccardo L.L., Antonio G. Role of Helicobacter pylori infection on nutrition and metabolism. World J. Gastroenterol. 2014;20(36):12809-12817. https://doi.org/10.3748/wjg. v20.i36.12809

83. Цуканов В.В., Тонких Ю.Л., Васютин А.В., Перетятько О.В., Пуликов А.С., Барон И.И. Структура слизистой оболочки желудка у пациентов с различными концентрациями и соотношениями пепсиногенов в сыворотке крови. Мед. сов. 2018;(14):114-117. https://doi.org/10.21518/2079701X-2018-14-114-117

84. Vannella L., Lahner E., Osborn J., Annibale B. Systematic review: gastric cancer incidence in pernicious anaemia. Aliment. Pharmacol. Ther. 2013;37:375-382. https://doi.org/10.1111/apt.12177

85. Lahner E., Persechino S., Annibale B. Micronutrients (Other than iron) and Helicobacter pylori infection: a systematic review. Helicobacter. 2012;17:1-15. https://doi.org/10.1111/j.1523-5378.2011.00892.x

86. Маев И.В., Андреев Д.Н., Кучерявый Ю.А. Инфекция Helicobacter pylori и экстрагастродуоденальные заболевания. Терапевт. арх. 2015;87(8):103-110. https://doi.org/10.17116/terarkh2015878103-110

87. Асатуров А.В., Варзин С.А., Строев Ю.И., Чурилов Л.П., Утехин В.И. Роль аутоиммунологической реактивности в патогенезе осложненных форм язвенной болезни у детей и взрослых. Педиатр. 2018;9(6):93-100. https://doi.org/10.17816/ PED9693-100

88. Terrell D.R., Beebe L.A., Neas B.R., Vesely S.K., Segal J.B., George J.N. Prevalence of primary immune thrombocytopenia in Oklahoma. Am. J. Hematol. 2012;87:848-852. https://doi.org/10.1002/ajh.23262

89. Psaila B., Bussel J.B. Immune thrombocytopenic purpura. Hematol. Oncol. Clin. North. Am. 2007;21:743-759. https://doi.org/10.1016/j.hoc.2007.06.007

90. Jang J.H., Kim J.Y., Mun Y.C., Bang S.M., Lim Y.J., Shin D.Y., Choi Y.B., Yhim H.Y., Lee J.W., Kook H., on the behalf of Korean Aplastic Anemia Working Party. Management of immune thrombocytopenia: Korean experts recommendation in 2017. Blood Res. 2017;52:254-263. https://doi.org/10.5045/br.2017.52.4.254

91. Fan H., Zhu H.L., Li S.X., Lu X.C., Zhai B., Guo B., Yao S.Q., Liu Y. Efficacy of amifostine in treating patients with idiopathic thrombocytopenia purpura. Cell Biochem. Biophys. 2011;59:7-12. https://doi.org/10.1007/ s12013-010-9100-5

92. Zain M.A., Zafar F., Ashfaq A., Jamil A.R., Ahmad A. Helicobacter pylori: An underrated Cause of immune thrombocytopenic purpura. A comprehensive review. Cureus. 2019;11(9):e5551. https://doi.org/10.7759/ cureus.5551

93. Pezeshki S., Saki N., Ghandali M.V., Ekrami A., Avarvand A.Y. Effect of Helicobacter Pylori eradication on patients with ITP: a meta-analysis of studies conducted in the Middle East. Blood Res. 2021;56:38-43. https://doi.org/10.5045/br.2021.2020189

94. Hwang J.J., Lee D.H., Yoon H., Shin C.M., Park Y.S., Kim N. The effects of Helicobacter pylori eradication therapy for chronic idiopathic thrombocytopenic purpura. Gut Liver. 2016;10(3):356-361. https://doi.org/10.5009/gnl14483

95. Franchini M., Veneri D. Helicobacter pylori-associated immune thrombocytopenia. Platelets. 2006;17:71-77. https://doi.org/10.1080/09537100500438057

96. Gasbarrini A., Franceschi F., Tartaglione R., Landolfi R., Pola P., Gasbarrini G. Regression of autoimmune thrombocytopenia after eradication of Helicobacter pylori. Lancet. 1998;352:878. https://doi.org/10.1016/ S0140-6736(05)60004-9

97. Noonavath R.N., Lakshmi Ch.P., Dutta T.K., Kate V. Helicobacter pylori eradication in patients with chronic immune thrombocytopenic purpura. World J. Gastroenterol. 2014;20(22):6918-6923. https://doi.org/10.3748/ wjg.v20.i22.6918

98. Aljarad S., Alhamid A., Tarabishi A.S., Tarabishi A.S. # 2, Suliman A., Aljarad Z. The impact of Helicobacter pylori eradication on platelet counts of adult patients with idiopathic thrombocytopenic purpura. BMC Hematol. 2018;18:28. https://doi.org/10.1186/s12878-0180119-y

99. Sheema K., Ikramdin U., Arshi N., Farah N., Imran S. Role of Helicobacter pylori eradication therapy on platelet recovery in chronic immune thrombocytopenic purpura. Gastroenterol. Res. Pract. 2017;2017:9529752. https://doi.org/10.1155/2017/9529752

100. Jackson S., Beck P.L., Pineo G.F., Poon M.C. Helicobacter pylori eradication: novel therapy for immune thrombocytopenic purpura? A review of the literature. Am. J. Hematol. 2005;78:142-150. https://doi.org/10.1002/ ajh.20250

101. Bettaieb A., Fromont P., Louache F., Oksenhendler E., Vainchenker W., Duédari N., Bierling P. Presence of cross-reactive antibody between human immunodeficiency virus (HIV) and platelet glycoproteins in HIV-related immune thrombocytopenic purpura. Blood. 1992;80(1):162-169.

102. Bettaieb A., Oksenhendler E., Duedari N., Bierling P. Cross-reactive antibodies between HIVgp120 and platelet gpIIIa (CD61) in HIV-related immune thrombocytopenic purpura. Clin. Exp. Immunol. 1996;103(1):19-23. https://doi.org/10.1046/j.13652249.1996.917606.x

103. Kim B.J, Kim H.S., Jang H.J., Kim J.H. Helicobacter pylori eradication in idiopathic thrombocytopenic purpura: a meta-analysis of randomized trials. Gastroenterology Research and Practice. 2018;2018:6090878. https://doi.org/10.1155/2018/6090878

104. Asahi A., Nishimoto T., Okazaki Y., Suzuki H., Masaoka T., Kawakami Y., Ikeda Y., Kuwana M. Helicobacter pylori eradication shifts monocyte Fcgamma receptor balance toward inhibitory FcgammaRIIB in immune thrombocytopenic purpura patients. J. Clin. Invest. 2008;118(8):2939-2949. https://doi.org/10.1172/JCI34496

105. Yamanishi S., Iizumi T., Watanabe E., Shimizu M., Kamiya S., Nagata K., Kumagai Y., Fukunaga Y., Takahashi H. Implications for induction of autoimmunity via activation of B-1 cells by Helicobacter pylori urease. Infect. Immun. 2006;74(1):248-256. https://doi.org/10.1128/IAI.74.1.248-256.2006

106. Rahman Y.A., Wahid Ahmed L.A., Hafez R.M., Ahmed R.M.M. Helicobacter pylori and its hematological effect. The Egyptian Journal of Internal Medicine. 2019;31:332-342. https://doi.org/10.4103/ejim.ejim_103_18

107. Byrne M.F., Kerrigan S.W., Corcoran P.A., Atherton J.C., Murray F.E., Fitzgerald D.J., Cox D.M. Helicobacter pylori binds von Willebrand factor and interacts with GPIb to induce platelet aggregation. Gastroenterology. 2003;124(7):1846-1854. https://doi.org/10.1016/ s0016-5085(03)00397-4

108. Scopel-Guerra A., Olivera-Severo D., Staniscuaski F., Uberti A.F., Callai-Silva N., Jaeger N., Porto B.N., Carlini C.R. The impact of Helicobacter pylori urease upon platelets and consequent contributions to inflammation. Front. Microbiol. 2017;8:2447. https://doi.org/10.3389/fmicb.2017.02447

109. Appelmelk B.J., van Die I., van Vliet S.J., Vandenbroucke-Grauls C.M., Geijtenbeek T.B., van Kooyk Y. Cutting edge: carbohydrate profiling identifies new pathogens that interact with dendritic cell-specific ICAM-3-grabbing nonintegrin on dendritic cells. J. Immunol. 2003;170(4):1635-1639. https://doi.org/10.4049/jimmunol.170.4.1635

110. Voland P., Hafsi N., Zeitner M., Laforsch S., Wagner H., Prinz C. Antigenic properties of HpaA and Omp18, two outer membrane proteins of Helicobacter pylori. Infect. Immun. 2003;71(7):3837-3843. https://doi.org/10.1128/IAI.71.7.3837-3843.2003

111. Holland R.L., Bosi K.D., Harpring G.H., Luo J., Wallig M., Phillips H., Blanke S.R. Chronic in vivo exposure to Helicobacter pylori VacA: Assessing the efficacy of automated and long-term intragastric toxin infusion. Sci. Rep. 2020;10:9307. https://doi.org/10.1038/ s41598-020-65787-3

112. Satoh K., Hirayama T., Takano K., SuzukiInoue K., Sato T., Ohta M., Nakagomi J., Ozaki Y. VacA, the vacuolating cytotoxin of Helicobacter pylori, binds to multimerin 1 on human platelets. Thromb. J. 2013;11:23. https://doi.org/10.1186/1477-9560-11-23

113. Frydman G.H., Davis N., Beck P.L., Fox J.G. Helicobacter pylori eradication in patients with immune thrombocytopenic ourpura: a review and the role of biogeography. Helicobacter. 2015;20:239-251. https://doi.org/10.1111/hel.12200

114. Veneri D., de Matteis G., Solero P., Federici F., Zanuso C., Guizzardi E., Arena S., Gaio M., Pontiero P., Ricetti M.M., Franchini M. Analysis of Band Tcell clonality and HLA class II alleles in patients with idiopathic thrombocytopenic purpura: correlation with Helicobacter pylori infection and response to eradication treatment. Platelets. 2005;16:307-311. https://doi.org/10.1080/09537100400028685

115. Sugano K., Tack J., Kuipers E.J., Graham D.Y., El-Omar E.M., Miura S., Haruma K., Asaka M., Uemura N., Malfertheineret P., faculty members of Kyoto Global Consensus Conference. Kyoto global consensus report on Helicobacter pylori gastritis. Gut. 2015; 64:1353-1367. https://doi.org/10.1136/gutjnl-2015-309252

116. Neunert C., Terrell D.R., Arnold D.M., Buchanan G., Cines D.B., Cooper N., Cuker A., Despotovic J.M., George J.N., Grace R.F., … Vesely S.K. American Society of Hematology 2019 guidelines for immune thrombocytopenia. Blood Adv. 2019;3:3829- 3866. https://doi.org/10.1182/bloodadvances.2019000966

117. Fock K.M., Katelaris P., Sugano K., Ang T.L., Hunt R., Talley N.J., Lam S.K., Xiao S.D., Tan H.J., Wu C.Y., … Second Asia-Pacific Conference. Second Asia-Pacific Consensus Guidelines for Helicobacter pylori infection. J. Gastroenterol. Hepatol. 2009;24:1587- 1600. https://doi.org/10.1111/j.1440-1746.2009.05982.x

118. Masataka K. Helicobacter pylori-associated immune thrombocytopenia: clinical features and pathogenic mechanisms. World J. Gastroenterol. 2014;20(3):714-723. https://doi.org/10.3748/wjg.v20.i3.714

119. Kuwana M. Helicobacter pylori-associated immune thrombocytopenia: clinical features and pathogenic mechanisms. World J. Gastroenterol. 2014;20:714-723. https://doi.org/10.3748/wjg.v20.i3.714

120. Национальное гематологическое общество, Национальное общество детских гематологов и онкологов. Клинические рекомендации. Железодефицитная анемия. Режим доступа: https://npngo.ru/uploads/media_document/636/161b822a-e1f64c71-a39b-975866e61ff8.docx

121. Национальное гематологическое общество, Национальное общество детских гематологов, онкологов. Клинические рекомендации. ВитаминB12-дефицитная анемия. Режим доступа: https://npngo.ru/uploads/media_document/634/bb602760b006-4983-a56e-c3bc333b6151.docx

122. Национальное гематологическое общество. Клинические рекомендации. Идиопатическая тромбоцитопеническая пурпура (ИТП) у взрослых. Режим доступа: https://npngo.ru/uploads/media_document/631/4a7a26c4-0f1b-4588-b2db-4b99d54d72e5. pdf