Antibodies to hepatitis B virus surface antigen and interleukin 12 and interleukin 18 gene polymorphisms in hemodialysis patients

BMC Nephrology

Paweł P Jagodziński²  Adrianna Mostowska²  Piotr M Wobszal¹  Alicja E Grzegorzewska¹ 

[1] Chair and Department of Nephrology, Transplantology and Internal Diseases Poznań University of Medical Sciences, 49 Przybyszewskiego Blvd, 60-355, Poznań, Poland;Department of Biochemistry and Molecular Biology, Poznań University of Medical Sciences, Poznań, Poland

关键词: Interleukin 18;    Interleukin 12;    Hemodialysis;    Gene polymorphisms;    Antibodies to surface antigen of hepatitis B virus;   

Others  :  1083138
DOI  :  10.1186/1471-2369-13-75

 received in 2011-11-02, accepted in 2012-07-28,  发布年份 2012

【 摘 要 】

Background

The interleukin (IL)18 rs360719 CC genotype is associated with the development of antibodies to hepatitis B virus surface antigen (anti-HBs) in hemodialysis (HD) patients. IL18 shares biological properties with IL12 in promoting the T-hepler 1 (Th1) system. We studied whether polymorphisms in the IL12A 3` untranslated region (UTR) and IL12B 3`UTR may contribute to anti-HBs development (titre ≥ 10 IU/L) in HD patients either individually or jointly with the IL18 polymorphism.

Methods

In 518 HD patients and 240 controls the IL12A rs568408 3’UTR G > A polymorphism was genotyped by high-resolution melting curve analysis. Polymerase chain reaction restriction fragment length polymorphism was used to detect the IL12B rs3212227 3’UTR A > C and IL18 -1297 T > C rs360719 polymorphisms. The associations between the IL12A, IL12B and IL18 genotypes and the risk of impaired anti-HBs development were estimated by computing the odds ratios and their 95% confidence intervals using logistic regression analysis.

Results

In the logistic regression analysis, the higher frequency of rs360719 CC individually (2.9% in 207 patients without anti-HBs development vs 8.0% in 311 patients with anti-HBs development, p = 0.009) and of rs360719 CC combined with rs568408 GG (p = 0.048), rs568408 GA (p = 0.035), rs568408 GG/AA (p = 0.034) or rs3212227 AA (p = 0.046) was associated with an increased chance for the development of anti-HBs in HD patients. Patients bearing both rs568408 AA and rs360719 TT had a 10.9-fold or 8.9-fold lower chance, respectively, to develop anti-HBs compared with those carrying any other genotype (p = 0.005) or those who had both wild-type rs568408 GG and rs360719 TT (p = 0.011). Carriers of both rs3212227 CC and rs360719 TC had a 4.6-fold lower chance for anti-HBs development than carriers of any other genotype (p = 0.042).

Conclusion

Development of anti-HBs in HD patients is associated with gene polymorphisms of interleukins involved in the Th1 system.

【 授权许可】

   
2012 Grzegorzewska et al.; licensee BioMed Central Ltd.

【 参考文献 】

• [1]Cooksley H, Chokshi S, Maayan Y, Wedemeyer H, Andreone P, Gilson R, Warnes T, Paganin S, Zoulim F, Frederick D, Neumann AU, Brosgart CL, Naoumov NV: Hepatitis B virus e antigen loss during adefovir dipivoxil therapy is associated with enhanced virus-specific CD4+ T-cell reactivity. Antimicrob Agents Chemother 2008, 52:312-320.
• [2]Wu JF, Wu TC, Chen CH, Ni YH, Chen HL, Hsu HY, Chang MH: Serum levels of interleukin-10 and interleukin-12 predict early, spontaneous hepatitis B virus e antigen seroconversion. Gastroenterology 2010, 138:165-172.
• [3]Rossol S, Marinos G, Carucci P, Singer MV, Roger W, Naoumov NV: Interleukin-12 induction of Th1 cytokines is important for viral clearance in chronic hepatitis B. J Clin Invest 1997, 99:3025-3033.
• [4]Cheong JY, Cho SW, Oh B, Kimm K, Lee KM, Shin SJ, Lee JA, Park BL, Cheong HS, Shin HD, Cho BY, Kim JH: Association of interleukin-18 gene polymorphisms with hepatitis B virus clearance. Dig Dis Sci 2010, 55:1113-1119.
• [5]Chow YH, Chiang BL, Lee YL, Chi WK, Lin WC, Chen YT, Tao MH: Development of Th1 and Th2 populations and the nature of immune responses to hepatitis B virus DNA vaccines can be modulated by codelivery of various cytokine genes. J Immunol 1998, 160:1320-1329.
• [6]Schirmbeck R, Reimann J: Modulation of gene-gun-mediated Th2 immunity to hepatitis B surface antigen by bacterial CpG motifs or IL-12. Intervirology 2001, 44:115-123.
• [7]Chen JZ, Zhu HH, Liu KZ, Chen Z: Enhancing cellular immune response to HBV M DNA vaccine in mice by codelivery of interleukin-18 recombinant. J Zhejiang Univ Sci 2004, 5:467-471.
• [8]Channarong S, Mitrevej A, Sinchaipanid N, Usuwantim K, Kulkeaw K, Chaicumpa W: Cloning, protein expression and immunogenicity of HBs-murine IL-18 fusion DNA vaccine. Asian Pac J Allergy Immunol 2007, 25:233-242.
• [9]Tang LL, Liu KZ: Recent advances in DNA vaccine of hepatitis virus. Hepatobiliary Pancreat Dis Int 2002, 1:228-231.
• [10]Okamura H, Tsutsi H, Komatsu T, Yutsudo M, Hakura A, Tanimoto T, Torigoe K, Okura T, Nukada Y, Hattori K, et al.: Cloning of a new cytokine that induces IFN-gamma production by T cells. Nature 1995, 378:88-91.
• [11]Yoshimoto T, Takeda K, Tanaka T, Ohkusu K, Kashiwamura S, Okamura H, Akira S, Nakanishi K: IL-12 up-regulates IL-18 receptor expression on T cells, Th1 cells, and B cells: synergism with IL-18 for IFN-gamma production. J Immunol 1998, 161:3400-3407.
• [12]Tominaga K, Yoshimoto T, Torigoe K, Kurimoto M, Matsui K, Hada T, Okamura H, Nakanishi K: IL-12 synergizes with IL-18 or IL-1beta for IFN-gamma production from human T cells. Int Immunol 2000, 12:151-160.
• [13]Kim JJ, Nottingham LK, Tsai A, Lee DJ, Maguire HC, Oh J, Dentchev T, Manson KH, Wyand MS, Agadjanyan MG, Ugen KE, Weiner DB: Antigen-specific humoral and cellular immune responses can be modulated in rhesus macaques through the use of IFN-gamma, IL-12, or IL-18 gene adjuvants. J Med Primatol 1999, 28:214-223.
• [14]Yang W, Chaudhri G, Jackson RJ, Karupiah G: IL-12p40 and IL-18 play pivotal roles in orchestrating the cell-mediated immune response to a Poxvirus infection. J Immunol 2009, 183:3324-3331.
• [15]Reading PC, Whitney PG, Barr DP, Wojtasiak M, Mintern JD, Waithman J, Brooks AG: IL-18, but not IL-12, regulates NK cell activity following intranasal herpes simplex virus type 1 infection. J Immunol 2007, 179:3214-3221.
• [16]Harandi AM, Svennerholm B, Holmgren J, Eriksson K: Interleukin-12 (IL-12) and IL-18 are important in innate defense against genital herpes simplex virus type 2 infection in mice but are not required for the development of acquired gamma interferon-mediated protective immunity. J Virol 2001, 75:6705-6709.
• [17]Sánchez E, Palomino-Morales RJ, Ortego-Centeno N, Jiménez-Alonso J, González-Gay MA, López-Nevot MA, Sánchez-Román J, de Ramón E, González-Escribano MF, Pons-Estel BA, D'Alfonso S: Sebastiani GD; Italian collaborative group, Alarcón-Riquelme ME, Martín J: Identification of a new putative functional IL18 gene variant through an association study in systemic lupus erythematosus. Hum Mol Genet 2009, 18:3739-3748.
• [18]Grzegorzewska AE, Wobszal P, Jagodziński PP: Interleukin-18 Promoter polymorphism and development of antibodies to surface antigen of hepatitis B virus in hemodialysis patients. Kidney Blood Press Res 2012, 35:1-8.
• [19]Recommendations for preventing transmission of infections among chronic hemodialysis patients: Morbidity and Mortality Weekly report. Centers for Disease Control and Prevention: Centers for Disease Control and Prevention; 2001:50.
• [20]Guidelines EBP: Prevention and management of HBV, HCV and HIV in HD patients. Nephrol Dial Transplant 2002, 17:78-87.
• [21]Załączniki do rozporządzenia Ministra Zdrowia z dnia 18 kwietnia 2005.
• [22]Hahn LW, Ritchie MD, Moore JH: Multifactor dimensionality reduction software for detecting gene-gene and gene-environment interactions. Bioinformatics 2003, 19:376-382.
• [23]Bruguera M, Cremades M, Mayor A, Sánchez Tapias JM, Rodés J: Immunogenicity of a recombinant hepatitis B vaccine in haemodialysis patients. Postgrad Med J 1987, 63S(2):155-158.
• [24]Mitwalli A: Responsiveness to hepatitis B vaccine in immunocompromised patients by doubling the dose scheduling. Nephron 1996, 73:417-420.
• [25]Sorkhi H, Roushan MR: Al Hashemi GH, Dooki MR, Bai S: Response to hepatitis B virus vaccination in haemodialysis patients with and without hepatitis C infection. East Mediterr Health J 2008, 14:798-803.
• [26]Fabrizi F, Messa PG, Lunghi G, Aucella F, Bisegna S, Mangano S, Villa M, Barbisoni F, Rusconi E, Martin P: Occult hepatitis B virus infection in dialysis patients: a multicentre survey. Aliment Pharmacol Ther 2005, 21:1341-1347.
• [27]Sun HY, Lee HC, Liu CE, Yang CL, Su SC, Ko WC, Lin CY, Tsai JJ, Wong WW, Ho MW, Cheng SH, Lin YH, Miao WJ, Hung CC: Factors associated with isolated anti-hepatitis B core antibody in HIV-positive patients: impact of compromised immunity. J Viral Hepat 2010, 17:578-587.
• [28]Grzegorzewska AE, Kaczmarek-Leki V, Młot-Michalska M, Niepolski L: Seroconversion rate to positivity for antibodies against core antigen of hepatitis B virus and duration of renal replacement therapy. Nephrol Dial Transplant 2011, 26:970-976.
• [29]Oesterreicher C, Hammer J, Koch U, Pfeffel F, Sunder-Plassmann G, Petermann D, Müller C: HBV and HCV genome in peripheral blood mononuclear cells in patients undergoing chronic hemodialysis. Kidney Int 1995, 48:1967-1971.
• [30]Minuk GY, Sun DF, Greenberg R, Zhang M, Hawkins K, Uhanova J, Gutkin A, Bernstein K, Giulivi A, Osiowy C: Occult hepatitis B virus infection in a North American adult hemodialysis patient population. Hepatology 2004, 40:1072-1077.
• [31]Grzegorzewska AE, Kurzawska-Firlej D, Ratajewski W, Frankiewicz D, Niepolski L, Kaczmarek A: Antibodies to core antigen of hepatitis B virus in patients on renal replacement therapy: Association with demographic, clinical and laboratory data. Nephron Clin Pract 2010, 114:c194-c203.
• [32]Fabrizi F, Dixit V, Martin P, Messa P: Meta-analysis: the impact of diabetes mellitus on the immunological response to hepatitis B virus vaccine in dialysis patients. Aliment Pharmacol Ther 2011, 33:815-821.
• [33]Shatat HZ, Kotkat AM, Farghaly AG: Immune response to hepatitis B vaccine in haemodialysis patients. J Egypt Public Health Assoc 2000, 75:257-275.
• [34]Steketee RW, Ziarnik ME, Davis JP: Seroresponse to hepatitis B vaccine in patients and staff of renal dialysis centers, Wisconsin. Am J Epidemiol 1988, 127:772-782.
• [35]Fabrizi F, Di Filippo S, Marcelli D, Guarnori I, Raffaele L, Crepaldi M, Erba G, Locatelli F: Recombinant hepatitis B vaccine use in chronic hemodialysis patients. Long-term evaluation and cost-effectiveness analysis. Nephron 1996, 72:536-543.
• [36]He Q, Wu F, Zhang P, Chen J: Effect of high-flux hemodialysis on delayed hepatitis B virus vaccination response in hemodialysis patients. Postgrad Med 2011, 123:150-152.
• [37]Watanabe H, Matsushita S, Kamikawaji N, Hirayama K, Okumura M, Sasazuki T: Immune suppression gene on HLA-Bw54-DR4-DRw53 haplotype controls nonresponsiveness in humans to hepatitis B surface antigen via CD8+ suppressor T cells. Hum Immunol 1988, 22:9-17.
• [38]Hatae K, Kimura A, Okubo R, Watanabe H, Erlich HA, Ueda K, Nishimura Y, Sasazuki T: Genetic control of nonresponsiveness to hepatitis B virus vaccine by an extended HLA haplotype. Eur J Immunol 1992, 22:1899-1905.
• [39]Girndt M, Sester U, Sester M, Deman E, Ulrich C, Kaul H, Köhler H: The interleukin-10 promoter genotype determines clinical immune function in hemodialysis patients. Kidney Int 2001, 60:2385-2391.
• [40]Seder RA, Gazzinelli R, Sher A, Paul WE: IL-12 acts directly on CD41 T cells to enhance priming for IFN-g production and diminishes IL-4 inhibition in such priming. Proc Natl Acad Sci USA 1993, 90:10188-10192.
• [41]Wysocka M, Kubin M, Vieira LQ, Ozmen L, Garotta G, Scott P, Trinchieri G: Interleukin-12 is required for interferon-gamma production and lethality in lipopolysaccharide-induced shock in mice. Eur J Immunol 1995, 25:672-676.
• [42]Cheema BS, Abas H, Smith BC, O'Sullivan AJ, Chan M, Patwardhan A, Kelly J, Gillin A, Pang G, Lloyd B, Berger K, Baune BT: Fiatarone Singh MA: Effect of resistance training during hemodialysis on circulating cytokines: a randomized controlled trial. Eur J Appl Physiol 2011, 111:1437-1445.
• [43]Ishizuka T, Nitta K, Yokoyama T, Hayashi T, Futatsuyama K, Kimata N, Miwa N, Nishida E, Kawashima A, Akiba T, Nihei H: Increased serum levels of interleukin-12 may be associated with Th1 differentiation in hemodialysis patients. Nephron 2002, 90:503-504.
• [44]Klínger J, Enríquez J, Arturo JA, Delgado M, Avila G, Ceballos O: Cytokines and peritonitis in continuous ambulatory peritoneal dialysis: immunodeviation and immunodeficiency. Adv Perit Dial 2002, 18:170-176.
• [45]Libetta C, Rampino T: Dal Canton A: Polarization of T-helper lymphocytes toward the Th2 phenotype in uremic patients. Am J Kidney Dis 2001, 38:286-295.
• [46]Sester U, Sester M, Hauk M, Kaul H, Köhler H, Girndt M: T-cell activation follows Th1 rather than Th2 pattern in haemodialysis patients. Nephrol Dial Transplant 2000, 15:1217-1223.
• [47]Lonnemann G, Novick D, Rubinstein M, Dinarello CA: Interleukin-18, interleukin-18 binding protein and impaired production of interferon-gamma in chronic renal failure. Clin Nephrol 2003, 60:327-334.
• [48]Liu L, Xu Y, Liu Z, Chen J, Zhang Y, Zhu J, Liu J, Liu S, Ji G, Shi H, Shen H, Hu Z: IL12 polymorphisms, HBV infection and risk of hepatocellular carcinoma in a high-risk Chinese population. Int J Cancer 2011, 128:1692-1696.
• [49]Morahan G, Huang D, Ymer SI, Cancilla MR, Stephen K, Dabadghao P, Werther G, Tait BD, Harrison LC, Colman PG: Linkage disequilibrium of a type 1 diabetes susceptibility locus with a regulatory IL12B allele. Nat Genet 2001, 27:218-221.
• [50]Davoodi-Semiromi A, Yang JJ, She JX: IL-12p40 is associated with type 1 diabetes in Caucasian-American families. Diabetes 2002, 51:2334-2336.
• [51]Seegers D, Zwiers A, Strober W, Peña AS, Bouma G: Taq I polymorphism in the 3_-UTR of the IL-12 p40 gene correlates with increased IL-12 secretion. Genes Immun 2002, 3:419-423.
• [52]Yilmaz V, Yentür SP, Saruhan-Direskeneli G: IL-12 and IL-10 polymorphisms and their effects on cytokine production. Cytokine 2005, 30:188-194.
• [53]Hennig BJ, Fielding K, Broxholme J, Diatta M, Mendy M, Moore C, Pollard AJ, Rayco-Solon P, Sirugo G, van der Sande MA, Waight P, Whittle HC, Zaman SM, Hill AV, Hall AJ: Host genetic factors and vaccine-induced immunity to hepatitis B virus infection. PLoS One 2008, 3:e1898.
• [54]Du DW, Jia ZS, Li GY, Zhou YY: HBV DNA vaccine with adjuvant cytokines induced specific immune responses against HBV infection. World J Gastroenterol 2003, 9:108-111.
• [55]Livingston BD, Alexander J, Crimi C, Oseroff C, Celis E, Daly K, Guidotti LG, Chisari FV, Fikes J, Chesnut RW, Sette A: Altered helper T lymphocyte function associated with chronic hepatitis B virus infection and its role in response to therapeutic vaccination in humans. J Immunol 1999, 162:3088-3095.
• [56]Izakovicova Holla L, Hrdlicková B, Schüller M, Buckova D, Kindlova D, Izakovic V, Vasku A: Haplotype analysis of the interleukin-18 gene in Czech patients with allergic disorders. Hum Immunol 2010, 71:592-597.