<i>Helicobacter pylori</i> induced Immune Thrombocytopenic Purpura and perspective role of <i>Helicobacter pylori</i> eradication therapy for treating Immune Thrombocytopenic Purpura

Arham Ihtesham; Shahzaib Maqbool; Muhammad Nadeem; Muhammad Bilawal Abbas Janjua; Omaima Sundus; Ali Bakht Naqqash; Waleed Inayat Mohamed; Syed Turab Haider; Muhmmad Ahmad; Mir Ahmad Talha Mustafa; Hafiz Osama Mehboob; Arham Ihtesham; Shahzaib Maqbool; Muhammad Nadeem; Muhammad Bilawal Abbas Janjua; Omaima Sundus; Ali Bakht Naqqash; Waleed Inayat Mohamed; Syed Turab Haider; Muhmmad Ahmad; Mir Ahmad Talha Mustafa; Hafiz Osama Mehboob

doi:10.3934/microbiol.2021018

AIMS Microbiology

2021, Volume 7, Issue 3: 284-303. doi: 10.3934/microbiol.2021018

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Review

Helicobacter pylori induced Immune Thrombocytopenic Purpura and perspective role of Helicobacter pylori eradication therapy for treating Immune Thrombocytopenic Purpura

1.
House officers Rawalpindi Medical University, Pakistan
2.
Consultant Pediatrician, THQ Kabirwala, Pakistan
3.
House officers Nishtar Medical University, Pakistan
4.
House officers Services Institute of Medical Sciences, Pakistan
5.
Medical Officer Holy Family Hospital Rawalpindi, Pakistan

Received: 01 July 2021 Accepted: 30 August 2021 Published: 02 September 2021

Immune thrombocytopenic purpura (ITP) is an autoimmune disease characterised by production of autoantibodies against platelet surface antigens. Recent studies have demonstrated a paramount association of ITP and Helicobacter pylori (H-pylori) infection with significant rise in platelet count following H-pylori eradication therapy. The H-pylori infection induced ITP is validated by many proposed mechanisms such as molecular mimicry due to production of autoantibodies against H-pylori surface virulent factors (CagA) and cross reactivity of these antibodies with platelet surface antigens (GP IIb/IIIa, GP Ib/IX, and GP Ia/IIa), phagocytic perturbation due to enhanced phagocytic activity of monocytes, enhanced dendritic cell numbers and response, platelets aggregation due to presence of anti- H-pylori IgG and von Willebrand factor (vWf) and finally host immune response against H-pylori virulent factors CagA and VacA leading to ITP. The effectiveness of H-pylori eradication therapy has also been demonstrated with platelet count being used as a predictive factor for assessment of treatment efficacy. Out of 201 patients 118 were responding to the triple therapy and remaining 83 patients were non-responders, showing the response rate of 58.7%. Out of 118 responders 69 patients were showing complete response (CR) and 49 were showing partial response (PR) to the H-pylori eradication therapy. However, more studies are required to elucidate this association and treatment efficacy.
- Helicobacter pylori,
- H-pylori eradication therapy,
- Immune thrombocytopenic purpura
Citation: Arham Ihtesham, Shahzaib Maqbool, Muhammad Nadeem, Muhammad Bilawal Abbas Janjua, Omaima Sundus, Ali Bakht Naqqash, Waleed Inayat Mohamed, Syed Turab Haider, Muhmmad Ahmad, Mir Ahmad Talha Mustafa, Hafiz Osama Mehboob. Helicobacter pylori induced Immune Thrombocytopenic Purpura and perspective role of Helicobacter pylori eradication therapy for treating Immune Thrombocytopenic Purpura[J]. AIMS Microbiology, 2021, 7(3): 284-303. doi: 10.3934/microbiol.2021018

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Abstract

Immune thrombocytopenic purpura (ITP) is an autoimmune disease characterised by production of autoantibodies against platelet surface antigens. Recent studies have demonstrated a paramount association of ITP and Helicobacter pylori (H-pylori) infection with significant rise in platelet count following H-pylori eradication therapy. The H-pylori infection induced ITP is validated by many proposed mechanisms such as molecular mimicry due to production of autoantibodies against H-pylori surface virulent factors (CagA) and cross reactivity of these antibodies with platelet surface antigens (GP IIb/IIIa, GP Ib/IX, and GP Ia/IIa), phagocytic perturbation due to enhanced phagocytic activity of monocytes, enhanced dendritic cell numbers and response, platelets aggregation due to presence of anti- H-pylori IgG and von Willebrand factor (vWf) and finally host immune response against H-pylori virulent factors CagA and VacA leading to ITP. The effectiveness of H-pylori eradication therapy has also been demonstrated with platelet count being used as a predictive factor for assessment of treatment efficacy. Out of 201 patients 118 were responding to the triple therapy and remaining 83 patients were non-responders, showing the response rate of 58.7%. Out of 118 responders 69 patients were showing complete response (CR) and 49 were showing partial response (PR) to the H-pylori eradication therapy. However, more studies are required to elucidate this association and treatment efficacy.

Ethical statement

Ethical values were considered in full capacity by each author of this study.

Conflict of interest

Authors have declared that they have no conflict of interest in disclosing their content.

Funding source

No funding was used for completion of this systematic review.

References

[1]	Terrell DR, Beebe LA, Neas BR, et al. (2012) Prevalence of primary immune thrombocytopenia in Oklahoma. Am J Hematol 87: 848-852. doi: 10.1002/ajh.23262
[2]	Psaila B, Bussel JB (2007) Immune thrombocytopenic purpura. Hematol/Oncol Clin North Am 21: 743-vii. doi: 10.1016/j.hoc.2007.06.007
[3]	Jang JH, Kim JY, Mun YC, et al. (2017) Management of immune thrombocytopenia: Korean experts recommendation in 2017. Blood Res 52: 254-263. doi: 10.5045/br.2017.52.4.254
[4]	Fan H, Zhu HL, Li SX, et al. (2011) Efficacy of amifostine in treating patients with idiopathic thrombocytopenia purpura. Cell Biochem Biophys 59: 7-12. doi: 10.1007/s12013-010-9100-5
[5]	Zain MA, Zafar F, Ashfaq A, et al. (2019) Helicobacter pylori: An underrated cause of Immune Thrombocytopenic Purpura. a comprehensive review. Cureus 11: e5551.
[6]	Pezeshki S, Saki N, Ghandali MV, et al. (2021) Effect of Helicobacter Pylori eradication on patients with ITP: a meta-analysis of studies conducted in the Middle East. Blood Res 56: 38-43. doi: 10.5045/br.2021.2020189
[7]	Rothenbacher D, Brenner H (2003) Burden of Helicobacter pylori and H. pylori-related diseases in developed countries: recent developments and future implications. Microbes Infect 5: 693-703. doi: 10.1016/S1286-4579(03)00111-4
[8]	Rothenbacher D, Winkler M, Gonser T, et al. (2002) Role of infected parents in transmission of helicobacter pylori to their children. The Pediatric Infect Dis J 21: 674-679. doi: 10.1097/00006454-200207000-00014
[9]	Burucoa C, Axon A (2017) Epidemiology of Helicobacter pylori infection. Helicobacter 22. doi: 10.1111/hel.12403
[10]	Vorobjova T, Ren Z, Dunkley M, et al. (2006) Response of IgG1 and IgG2 subclasses to Helicobacter pylori in subjects with chronic inflammation of the gastric mucosa, atrophy and gastric cancer in a country with high Helicobacter pylori infection prevalence. APMIS 114: 372-380. doi: 10.1111/j.1600-0463.2006.apm_392.x
[11]	Pasceri V, Cammarota G, Patti G, et al. (1998) Association of virulent Helicobacter pylori strains with ischemic heart disease. Circulation 97: 1675-1679. doi: 10.1161/01.CIR.97.17.1675
[12]	Annibale B, Lahner E, Bordi C, et al. (2000) Role of Helicobacter pylori infection in pernicious anaemia. Dig Liver Dis 32: 756-762. doi: 10.1016/S1590-8658(00)80351-5
[13]	Gasbarrini A, Franceschi F, Tartaglione R, et al. (1998) Regression of autoimmune thrombocytopenia after eradication of Helicobacter pylori. Lancet 352: 878. doi: 10.1016/S0140-6736(05)60004-9
[14]	Panic N, Leoncini E, de Belvis G, et al. (2013) Evaluation of the endorsement of the preferred reporting items for systematic reviews and meta-analysis (PRISMA) statement on the quality of published systematic review and meta-analyses. PloS one 8: e83138. doi: 10.1371/journal.pone.0083138
[15]	George JN, Woolf SH, Raskob GE, et al. (1996) Idiopathic thrombocytopenic purpura: a practice guideline developed by explicit methods for the American Society of Hematology. Blood 88: 3-40. doi: 10.1182/blood.V88.1.3.3
[16]	Aljarad S, Alhamid A, Sankari Tarabishi A, et al. (2018) The impact of helicobacter pylori eradication on platelet counts of adult patients with idiopathic thrombocytopenic purpura. BMC Hematol 18: 28. doi: 10.1186/s12878-018-0119-y
[17]	Sheema K, Ikramdin U, Arshi N, et al. (2017) Role of Helicobacter pylori eradication therapy on platelet recovery in chronic immune thrombocytopenic purpura. Gastroenterol Res Pract 2017: 9529752. doi: 10.1155/2017/9529752
[18]	Jackson S, Beck PL, Pineo GF, et al. (2005) Helicobacter pylori eradication: novel therapy for immune thrombocytopenic purpura? A review of the literature. Am J Hematol 78: 142-150. doi: 10.1002/ajh.20250
[19]	Bettaieb A, Fromont P, Louache F, et al. (1992) Presence of cross-reactive antibody between human immunodeficiency virus (HIV) and platelet glycoproteins in HIV-related immune thrombocytopenic purpura. Blood 80: 162-169. doi: 10.1182/blood.V80.1.162.162
[20]	Bettaieb A, Oksenhendler E, Duedari N, et al. (1996) Cross-reactive antibodies between HIV-gp120 and platelet gpIIIa (CD61) in HIV-related immune thrombocytopenic purpura. Clin Exp Immunol 103: 19-23. doi: 10.1046/j.1365-2249.1996.917606.x
[21]	Asahi A, Nishimoto T, Okazaki Y, et al. (2008) Helicobacter pylori eradication shifts monocyte Fcgamma receptor balance toward inhibitory FcgammaRIIB in immune thrombocytopenic purpura patients. J Clini Invest 118: 2939-2949.
[22]	Yamanishi S, Iizumi T, Watanabe E, et al. (2006) Implications for induction of autoimmunity via activation of B-1 cells by Helicobacter pylori urease. Infect Immun 74: 248-256. doi: 10.1128/IAI.74.1.248-256.2006
[23]	Appelmelk BJ, van Die I, van Vliet SJ, et al. (2003) Cutting edge: carbohydrate profiling identifies new pathogens that interact with dendritic cell-specific ICAM-3-grabbing nonintegrin on dendritic cells. J Immunol 170: 1635-1639. doi: 10.4049/jimmunol.170.4.1635
[24]	Voland P, Hafsi N, Zeitner M, et al. (2003) Antigenic properties of HpaA and Omp18, two outer membrane proteins of Helicobacter pylori. Infect Immun 71: 3837-3843. doi: 10.1128/IAI.71.7.3837-3843.2003
[25]	Byrne MF, Kerrigan SW, Corcoran PA, et al. (2003) Helicobacter pylori binds von Willebrand factor and interacts with GPIb to induce platelet aggregation. Gastroenterology 124: 1846-1854. doi: 10.1016/S0016-5085(03)00397-4
[26]	Hessey SJ, Spencer J, Wyatt JI, et al. (1990) Bacterial adhesion and disease activity in Helicobacter associated chronic gastritis. Gut 31: 134-138. doi: 10.1136/gut.31.2.134
[27]	Guruge JL, Falk PG, Lorenz RG, et al. (1998) Epithelial attachment alters the outcome of Helicobacter pylori infection. Proceedings of the National Academy of Sciences of the United States of America 95: 3925-3930. doi: 10.1073/pnas.95.7.3925
[28]	Andersen LP (2007) Colonization and infection by Helicobacter pylori in humans. Helicobacter 12: 12-15. doi: 10.1111/j.1523-5378.2007.00574.x
[29]	Odenbreit S, Püls J, Sedlmaier B, et al. (2000) Translocation of Helicobacter pylori CagA into gastric epithelial cells by type IV secretion. Science 287: 1497-1500. doi: 10.1126/science.287.5457.1497
[30]	Asahi M, Azuma T, Ito S, et al. (2000) Helicobacter pylori CagA protein can be tyrosine phosphorylated in gastric epithelial cells. J Exp Med 191: 593-602. doi: 10.1084/jem.191.4.593
[31]	Tummuru MK, Sharma SA, Blaser MJ (1995) 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 18: 867-876. doi: 10.1111/j.1365-2958.1995.18050867.x
[32]	Holland RL, Bosi KD, Harpring GH, et al. (2020) Chronic in vivo exposure to Helicobacter pylori VacA: Assessing the efficacy of automated and long-term intragastric toxin infusion. Sci Rep 10: 9307. doi: 10.1038/s41598-020-65787-3
[33]	Satoh K, Hirayama T, Takano K, et al. (2013) VacA, the vacuolating cytotoxin of Helicobacter pylori, binds to multimerin 1 on human platelets. Thromb J 11: 23. doi: 10.1186/1477-9560-11-23
[34]	Frydman GH, Davis N, Beck PL, et al. (2015) Helicobacter pylori eradication in patients with immune thrombocytopenic ourpura: a review and the role of biogeography. Helicobacter 20: 239-251. doi: 10.1111/hel.12200
[35]	Veneri D, De Matteis G, Solero P, et al. (2005) Analysis of B- and T-cell clonality and HLA class II alleles in patients with idiopathic thrombocytopenic purpura: correlation with Helicobacter pylori infection and response to eradication treatment. Platelets 16: 307-311. doi: 10.1080/09537100400028685
[36]	Malfertheiner P, Megraud F, O'Morain, CA, et al. (2012) Management of Helicobacter pylori infection--the Maastricht IV/Florence consensus report. Gut 61: 646-664. doi: 10.1136/gutjnl-2012-302084
[37]	Neunert C, Terrell DR, Arnold DM, et al. (2019) American Society of Hematology 2019 guidelines for immune thrombocytopenia. Blood Adv 3: 3829-3866. doi: 10.1182/bloodadvances.2019000966
[38]	Fock KM, Katelaris P, Sugano K, et al. (2009) Second Asia-Pacific Consensus Guidelines for Helicobacter pylori infection. J Gastroenterol Hepatol 24: 1587-1600. doi: 10.1111/j.1440-1746.2009.05982.x
[39]	Cohen YC, Djulbegovic B, Shamai-Lubovitz O, et al. (2000) The bleeding risk and natural history of idiopathic thrombocytopenic purpura in patients with persistent low platelet counts. Arch Intern Med 160: 1630-1638. doi: 10.1001/archinte.160.11.1630
[40]	Provan D, Stasi R, Newland AC, et al. (2010) International consensus report on the investigation and management of primary immune thrombocytopenia. Blood 115: 168-186. doi: 10.1182/blood-2009-06-225565
[41]	Maghbool M, Maghbool M, Shahriari M, et al. (2009) Does Helicobacter pylori play a role in the pathogenesis of childhood chronic idiopathic thrombocytopenic purpura? Pediatric Rep 1: e2.
[42]	Goto H, Kikuta T, Ota A, et al. (2001) Successful treatment of refractory idiopathic thrombocytopenic purpura by eradication of Helicobacter pylori. Rinsho Ketsueki 42: 1192-1194.
[43]	Hwang JJ, Lee DH, Yoon H, et al. (2016) The Effects of Helicobacter pylori Eradication Therapy for Chronic IdiopathicThrombocytopenic Purpura. Gut Liver 10: 356-361. doi: 10.5009/gnl14483
[44]	Veneri D, Franchini M, Gottardi M, et al. (2002) Efficacy of Helicobacter pylori eradication in raising platelet count in adult patients with idiopathic thrombocytopenic purpura. Haematologica 87: 1177-1179.
[45]	Samson AD, Arend SM, Zwaginga JJ, et al. (2012) Helicobacter pylori geïnduceerde trombocytopenie. Ned Tijdschr Geneeskd 156: A4799.
[46]	Jaing TH, Yang CP, Hung IJ, et al. (2003) Efficacy of Helicobacter pylori eradication on platelet recovery in children with chronic idiopathic thrombocytopenic purpura. Acta Paediatr 92: 1153-1157. doi: 10.1111/j.1651-2227.2003.tb02476.x
[47]	Ando K, Shimamoto T, Tauchi T, et al. (2003) Can eradication therapy for Helicobacter pylori really improve the thrombocytopenia in idiopathic thrombocytopenic purpura? Our experience and a literature review. Int J Hematol 77: 239-244. doi: 10.1007/BF02983780
[48]	Hashino S, Mori A, Suzuki S, et al. (2003) Platelet recovery in patients with idiopathic thrombocytopenic purpura after eradication of Helicobacter pylori. Int Hematol 77: 188-191. doi: 10.1007/BF02983220
[49]	Tag HS, Lee HS, Jung SH, et al. (2010) Effects of Helicobacter pylori eradication in patients with immune thrombocytopenic purpura. Korean J Hematol 45: 127-132. doi: 10.5045/kjh.2010.45.2.127
[50]	Payandeh M, Sohrabi N, Zare ME, et al. (2012) Platelet Count Response to Helicobacter pylori Eradication in Iranian Patients with Idiopathic Thrombocytopenic Purpura. Mediterr J Hematol Infect Dis 4: e2012056. doi: 10.4084/mjhid.2012.056
[51]	Lee A, Hong J, Chung H, et al. (2020) Helicobacter pylori eradication affects platelet count recovery in immune thrombocytopenia. Sci Rep 10: 9370. doi: 10.1038/s41598-020-66460-5
[52]	Payandeh M, Raeisi D, Sohrabi N, et al. (2013) Poor platelet count response to Helicobacter Pylori eradication in patients with severe idiopathic thrombocytopenic purpura. Int J Hematol-Oncol Stem Cell Res 7: 9-14.
[53]	Rodeghiero F, Stasi R, Gernsheimer T, et al. (2009) Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. Blood 113: 2386-2393. doi: 10.1182/blood-2008-07-162503
[54]	Song MK, Chung JS, Shin HJ, et al. (2008) Outcome of immunosuppressive therapy with Helicobacter pylori eradication therapy in patients with chronic idiopathic thrombocytopenic purpura. J Korean Med Sci 23: 445-451. doi: 10.3346/jkms.2008.23.3.445
[55]	Sato R, Murakami K, Watanabe K, et al. (2004) Effect of Helicobacter pylori eradication on platelet recovery in patients with chronic idiopathic thrombocytopenic purpura. Arch Inter Med 164: 1904-1907. doi: 10.1001/archinte.164.17.1904

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