rs1800890 Polymorphism of IL-10 and Susceptibility to Idiopathic Thrombocytopenic Purpura

Abstract

Immune thrombocytopenic purpura (ITP) is an immune bleeding disorder that is reported in approximately 2 out of every 100,000 adults with a mean age of 50 years. Several factors such as various genetic backgrounds are associated with the pathogenesis of ITP. Interleukin (IL)-10 is a complicated cytokine that has a role in tumor progression, antitumor immunity, and immune system regulation. rs1800890 is an IL-10 single nucleotide polymorphism linked to lower levels of IL-10. A total of 67 patients with ITP and 70 healthy individuals (controls) were considered in this study. The IL-10 polymorphism was detected by the amplification refractory mutation system–polymerase chain reaction technique. According to our analysis, individual carriers of the AA genotype were less likely to develop ITP. The AT genotype was more common in patients with ITP in comparison to the control group. However, there was no significant association between rs1800890 genotypes (p = 0.775, odds ratio =1.517, 95%) in the acute and chronic groups. We observed that women had a higher mean frequency of this polymorphism (p = 0.0012). The rs1800890 AA genotype was associated with the highest platelet counts. However, the mean platelet volume and platelet distribution width values among alleles of the polymorphisms did not vary significantly. The IL-10 rs1800890 polymorphism may have a role in idiopathic thrombocytopenic purpura etiology. As a result, more research with a larger number of sample sizes is suggested.

Keywords

genotype - immune thrombocytopenic purpura - megakaryocyte - IL-10 - platelet - polymorphism

Publication History

Received: 04 July 2022

Accepted: 26 July 2023

Article published online:
29 September 2023

• References

• 1 Terrell DR, Beebe LA, Vesely SK, Neas BR, Segal JB, George JN. The incidence of immune thrombocytopenic purpura in children and adults: a critical review of published reports. Am J Hematol 2010; 85 (03) 174-180
• 2 Onisâi M, Vlădăreanu A-M, Spînu A, Găman M, Bumbea H. Idiopathic thrombocytopenic purpura (ITP) - new era for an old disease. Rom J Intern Med 2019; 57 (04) 273-283
• 3 Ramírez-López A, Álvarez Román MT, Monzón Manzano E. et al. The importance of platelet glycoside residues in the haemostasis of patients with immune thrombocytopaenia. J Clin Med 2021; 10 (08) 1661
• 4 Neylon AJ, Saunders PW, Howard MR, Proctor SJ, Taylor PR. Northern Region Haematology Group. Clinically significant newly presenting autoimmune thrombocytopenic purpura in adults: a prospective study of a population-based cohort of 245 patients. Br J Haematol 2003; 122 (06) 966-974
• 5 Perera M, Garrido T. Advances in the pathophysiology of primary immune thrombocytopenia. Hematology 2017; 22 (01) 41-53
• 6 Provan D, Newland AC. Current management of primary immune thrombocytopenia. Adv Ther 2015; 32 (10) 875-887
• 7 Rodeghiero F. Is ITP a thrombophilic disorder?. Am J Hematol 2016; 91 (01) 39-45
• 8 Akbayram S, Dogan M, Ustyol L. et al. The clinical outcome of 260 pediatric ITP patients in one center. Clin Appl Thromb Hemost 2011; 17 (06) E30-E35
• 9 Zainal A, Salama A, Alweis R. Immune thrombocytopenic purpura. J Community Hosp Intern Med Perspect 2019; 9 (01) 59-61
• 10 Cortelazzo S, Finazzi G, Buelli M, Molteni A, Viero P, Barbui T. High risk of severe bleeding in aged patients with chronic idiopathic thrombocytopenic purpura. Blood 1991; 77 (01) 31-33
• 11 Aledort LM, Hayward CP, Chen MG, Nichol JL, Bussel J. ITP Study Group. Prospective screening of 205 patients with ITP, including diagnosis, serological markers, and the relationship between platelet counts, endogenous thrombopoietin, and circulating antithrombopoietin antibodies. Am J Hematol 2004; 76 (03) 205-213
• 12 Yusufjanovich EU, Irisbaevich MG, Rafiqovich ZA. et al. IDIOPATHIC THROMBOCYTOPENIC PURPURA IN PREGNANCY. In: E Conference Zone; 2023: 13-20
• 13 Chandrakala S, Toshniwal M, Halvawala M. et al. Efficacy and safety of biosimilar romiplostim versus innovator romiplostim in patients with chronic immune thrombocytopenia. Indian J Hematol Blood Transfus 2023; 66 (01) 96-100
• 14 Zufferey A, Kapur R, Semple JW. Pathogenesis and therapeutic mechanisms in immune thrombocytopenia (ITP). J Clin Med 2017; 6 (02) 16
• 15 Kim TO, Flanagan JM, Habibi A. et al. Genetic variants in toll-like receptor 4 are associated with lack of steroid-responsiveness in pediatric ITP patients. Am J Hematol 2020; 95 (04) 395-400
• 16 Cines DB, Blanchette VS. Immune thrombocytopenic purpura. N Engl J Med 2002; 346 (13) 995-1008
• 17 Olsson B, Andersson P-O, Jernås M. et al. T-cell-mediated cytotoxicity toward platelets in chronic idiopathic thrombocytopenic purpura. Nat Med 2003; 9 (09) 1123-1124
• 18 Semple JW, Freedman J. Increased antiplatelet T helper lymphocyte reactivity in patients with autoimmune thrombocytopenia. Blood 1991; 78 (10) 2619-2625
• 19 Cines DB, Cuker A, Semple JW. Pathogenesis of immune thrombocytopenia. Presse Med 2014; 43 (4 Pt 2): e49-e59
• 20 Zhang H-Y, Hou M, Zhang X-H, Guan XH, Sun GZ. [The diagnostic value of platelet glycoprotein-specific autoantibody detection in idiopathic thrombocytopenic purpura]. Zhongguo Shi Yan Xue Ye Xue Za Zhi 2004; 12 (02) 204-206
• 21 Khodadi E, Asnafi AA, Shahrabi S, Shahjahani M, Saki N. Bone marrow niche in immune thrombocytopenia: a focus on megakaryopoiesis. Ann Hematol 2016; 95 (11) 1765-1776
• 22 Wang N, Li GN, Wang XB, Liang T, Hu L. TNF-α promoter single nucleotide polymorphisms and haplotypes associate with susceptibility of immune thrombocytopenia in Chinese adults. Hum Immunol 2014; 75 (09) 980-985
• 23 Johnsen J. Pathogenesis in immune thrombocytopenia: new insights. Hematology (Am Soc Hematol Educ Program) 2012; 2012: 306-312
• 24 Hashimoto SI, Komuro I, Yamada M, Akagawa KS. IL-10 inhibits granulocyte-macrophage colony-stimulating factor-dependent human monocyte survival at the early stage of the culture and inhibits the generation of macrophages. J Immunol 2001; 167 (07) 3619-3625
• 25 de Waal Malefyt R, Abrams J, Bennett B, Figdor CG, de Vries JE. Interleukin 10(IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. J Exp Med 1991; 174 (05) 1209-1220
• 26 Li X, Lu P, Li B. et al. Interleukin 2 and interleukin 10 function synergistically to promote CD8⁺ T cell cytotoxicity, which is suppressed by regulatory T cells in breast cancer. Int J Biochem Cell Biol 2017; 87: 1-7
• 27 Fillatreau S, Sweenie CH, McGeachy MJ, Gray D, Anderton SM. B cells regulate autoimmunity by provision of IL-10. Nat Immunol 2002; 3 (10) 944-950
• 28 Macatonia SE, Doherty TM, Knight SC, O'Garra A. Differential effect of IL-10 on dendritic cell-induced T cell proliferation and IFN-gamma production. J Immunol 1993; 150 (09) 3755-3765
• 29 Asadullah K, Sterry W, Stephanek K. et al. IL-10 is a key cytokine in psoriasis. Proof of principle by IL-10 therapy: a new therapeutic approach. J Clin Invest 1998; 101 (04) 783-794
• 30 DeBruyne LA, Li K, Chan SY, Qin L, Bishop DK, Bromberg JS. Lipid-mediated gene transfer of viral IL-10 prolongs vascularized cardiac allograft survival by inhibiting donor-specific cellular and humoral immune responses. Gene Ther 1998; 5 (08) 1079-1087
• 31 Katsikis PD, Chu C-Q, Brennan FM, Maini RN, Feldmann M. Immunoregulatory role of interleukin 10 in rheumatoid arthritis. J Exp Med 1994; 179 (05) 1517-1527
• 32 Topbaş N. Ataksi telenjiektazili hastaların klinik ve laboratuvar özellikleri. 2022
• 33 Swiątek BJ. Is interleukin-10 gene polymorphism a predictive marker in HCV infection?. Cytokine Growth Factor Rev 2012; 23 (1-2): 47-59
• 34 Audia S, Mahévas M, Samson M, Godeau B, Bonnotte B. Pathogenesis of immune thrombocytopenia. Autoimmun Rev 2017; 16 (06) 620-632
• 35 Hong P, Feng W-Y, Fu L-H, Jin J, Fu JP. Associations between genetic polymorphisms in interleukin-10 and hematological oncology: evidence from a meta-analysis. Cancer Biol Ther 2020; 21 (04) 372-378
• 36 Lv T-T, Wu J, Li J. et al. Association of interleukin-10 gene single nucleotide polymorphisms with susceptibility to systemic lupus erythematosus in a Chinese population. Gene 2018; 642: 549-554
• 37 Zhang T-P, Lv T-T, Xu S-Z, Pan HF, Ye DQ. Association of interleukin-10 gene single nucleotide polymorphisms with rheumatoid arthritis in a Chinese population. Postgrad Med J 2018; 94 (1111): 284-288
• 38 Mokhtar GM, El-Beblawy NM, Adly AA, Elbarbary NS, Kamal TM, Hasan EM. Cytokine gene polymorphism [tumor necrosis factor-alpha (-308), IL-10 (-1082), IL-6 (-174), IL-17F, 1RaVNTR] in pediatric patients with primary immune thrombocytopenia and response to different treatment modalities. Blood Coagul Fibrinolysis 2016; 27 (03) 313-323
• 39 Makhlouf MM, Abd Elhamid SM. Expression of IL4 (VNTR intron 3) and IL10 (-627) genes polymorphisms in childhood immune thrombocytopenic purpura. Lab Med 2014; 45 (03) 211-219
• 40 Tesse R, Del Vecchio GC, De Mattia D, Sangerardi M, Valente F, Giordano P. Association of interleukin-(IL)10 haplotypes and serum IL-10 levels in the progression of childhood immune thrombocytopenic purpura. Gene 2012; 505 (01) 53-56
• 41 Miltiadous O, Hou M, Bussel JB. Identifying and treating refractory ITP: difficulty in diagnosis and role of combination treatment. Blood 2020; 135 (07) 472-490
• 42 LeVine DN, Brooks MB. Immune thrombocytopenia (ITP): Pathophysiology update and diagnostic dilemmas. Vet Clin Pathol 2019; 48 (Suppl. 01) 17-28
• 43 Neunert C, Lim W, Crowther M, Cohen A, Solberg Jr L, Crowther MA. American Society of Hematology. The American Society of Hematology 2011 evidence-based practice guideline for immune thrombocytopenia. Blood 2011; 117 (16) 4190-4207
• 44 Cines DB, Bussel JB, Liebman HA, Luning Prak ET. The ITP syndrome: pathogenic and clinical diversity. Blood 2009; 113 (26) 6511-6521
• 45 Chen X, Xu J, Chen Z. et al. Interferon-γ +874A/T and interleukin-4 intron3 VNTR gene polymorphisms in Chinese patients with idiopathic thrombocytopenic purpura. Eur J Haematol 2007; 79 (03) 191-197
• 46 Li F, Ji L, Wang W. et al. Insufficient secretion of IL-10 by Tregs compromised its control on over-activated CD4+ T effector cells in newly diagnosed adult immune thrombocytopenia patients. Immunol Res 2015; 61 (03) 269-280
• 47 Pehlivan M, Okan V, Sever T. et al. Investigation of TNF-alpha, TGF-beta 1, IL-10, IL-6, IFN-gamma, MBL, GPIA, and IL1A gene polymorphisms in patients with idiopathic thrombocytopenic purpura. Platelets 2011; 22 (08) 588-595
• 48 Cho MJ, Ellebrecht CT, Payne AS. The dual nature of interleukin-10 in pemphigus vulgaris. Cytokine 2015; 73 (02) 335-341
• 49 Zhao H, Zhang Y, Xiao G, Wu N, Xu J, Fang Z. Interleukin-18 gene promoter–607 A/C polymorphism and the risk of immune thrombocytopenia. Autoimmunity 2014; 47 (07) 478-481
• 50 Zhang D, Zhang X, Ge M. et al. The polymorphisms of T cell-specific TBX21 gene may contribute to the susceptibility of chronic immune thrombocytopenia in Chinese population. Hum Immunol 2014; 75 (02) 129-133
• 51 Soliman MA, Helwa MA, Fath-Allah SK, El-Hawy MA, Badr HS, Barseem NF. IL-10 polymorphisms and T-cell subsets could affect the clinical presentation and outcome of childhood immune thrombocytopenia in Egyptian population. APMIS 2018; 126 (05) 380-388
• 52 Morgan DS, Afifi RA-R-A, El-Hoseiny SM, Amin DG, Ibrahim SYG. The potential association of tumor necrosis factor-βeta (252 G/A) cytokine gene polymorphism with immune thrombocytopenic purpura among Egyptian children. Hematology 2018; 23 (05) 299-303
• 53 Holster A, Teräsjärvi J, Vuononvirta J. et al. Polymorphisms in the promoter region of IL10 gene are associated with virus etiology of infant bronchiolitis. World J Pediatr 2018; 14 (06) 594-600
• 54 Nielsen KR, Steffensen R, Haunstrup TM. et al. Inherited variation in immune response genes in follicular lymphoma and diffuse large B-cell lymphoma. Leuk Lymphoma 2015; 56 (12) 3257-3266
• 55 El Ghannam D, Fawzy IM, Azmy E, Hakim H, Eid I. Relation of interleukin-10 promoter polymorphisms to adult chronic immune thrombocytopenic purpura in a cohort of Egyptian population. Immunol Invest 2015; 44 (07) 616-626
• 56 Dai Z-M, He A-L, Zhang W-G. et al. Association of the four common polymorphisms in interleukin-10 (rs1800890, rs1800896, rs1800871, and rs1800872) with non-Hodgkin's lymphoma risk: a meta-analysis. Int J Clin Exp Med 2014; 7 (12) 4720-4733
• 57 Raedler D, Illi S, Pinto LA. et al. IL10 polymorphisms influence neonatal immune responses, atopic dermatitis, and wheeze at age 3 years. J Allergy Clin Immunol 2013; 131 (03) 789-796
• 58 Tsilidis KK, Helzlsouer KJ, Smith MW. et al. Association of common polymorphisms in IL10, and in other genes related to inflammatory response and obesity with colorectal cancer. Cancer Causes Control 2009; 20 (09) 1739-1751
• 59 Wang MH, Helzlsouer KJ, Smith MW. et al. Association of IL10 and other immune response- and obesity-related genes with prostate cancer in CLUE II. Prostate 2009; 69 (08) 874-885
• 60 Lin P-W, Huang C-M, Huang C-C. et al. The association of -627 interleukin-10 promoter polymorphism in Chinese patients with systemic lupus erythematosus. Clin Rheumatol 2007; 26 (03) 298-301
• 61 Domingues W, Kanunfre KA, Rodrigues JC, Teixeira LE, Yamamoto L, Okay TS. Preliminary report on the putative association of IL10–3575 T/A genetic polymorphism with malaria symptoms. Rev Inst Med Trop São Paulo 2016; 58: 30