Association of the interleukin-12 polymorphic variants with the development of antibodies to surface antigen of hepatitis B virus in hemodialysis patients in response to vaccination or infection

Molecular Biology Reports, Dec 2013

Cytokines, involved in the T-helper 1 system, play a role in the regulation of hepatitis B virus (HBV) clearance and the immune response to HBV antigens during natural infection or planned vaccination. Our aim was to examine whether the polymorphic variants of IL-12 are equally associated with development of antibodies to HBV surface antigen (anti-HBs) in hemodialysis (HD) patients in the case of HBV vaccination or HBV infection. The IL-12A rs568408 and IL-12B rs3212227 polymorphisms were analyzed in relation to anti-HBs development in 602 HD patients with negative antibodies to HBV core antigen (anti-HBc) who were hepatitis B vaccinated (group I) as well as in 237 anti-HBc positive HD patients who were infected with HBV in the past (group II). In group I, 199 patients did not develop an anti-HBs titre >10 IU/L (subgroup Ia), whereas in group II, 55 patients did not develop an anti-HBs titre >10 IU/L (subgroup IIa). Patients of groups I and II that developed an anti-HBs >10 IU/L were included into subgroups Ib and IIb, respectively. In hepatitis B vaccinated HD patients, development of a protective anti-HBs titre was positively associated with vintage of renal replacement therapy (RRT), chronic glomerulonephritis as a cause of RRT, and GA rs 568408 IL-12A (OR 1.6, 95 % CI 1.0–2.5, P = 0.035), but a frequency distribution of this genotype between responders and non-responders was not significant when the Bonferroni correction was applied. In HBV infected HD patients, anti-HBs development was positively associated with AC rs3212227 IL-12B (OR 8.0, 95 % CI 2.6–24.9, P < 0.001), whereas HBsAg positivity, AA rs3212227 IL-12B (OR 0.3, 95 % CI 0.1–0.7, P = 0.007), and CC rs3212227 IL-12B (OR 0.1, 95 % CI 0.03–0.6, P = 0.011) were negative predictors of positive anti-HBs phenotype. When the Bonferroni correction was applied, if appropriate, these associations remained significant. In HD patients, the studied IL-12 polymorphic variants seem to be associated with the anti-HBs phenotype (a) with borderline significance for IL-12A in hepatitis B vaccinated patients, and (b) significantly for IL-12B in patients who underwent natural HBV infection.

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Association of the interleukin-12 polymorphic variants with the development of antibodies to surface antigen of hepatitis B virus in hemodialysis patients in response to vaccination or infection

Alicja E. Grzegorzewska 0 1 2 Piotr M. Wobszal 0 1 2 Anna Sowin ska 0 1 2 Adrianna Mostowska 0 1 2 Pawe P. Jagodzin ski 0 1 2 0 A. Sowinska Department of Computer Science and Statistics, Poznan University of Medical Sciences , 79 Dabrowskiego Str, 60-529 Poznan, Poland 1 A. E. Grzegorzewska (&) P. M. Wobszal Department of Nephrology, Transplantology and Internal Diseases, Poznan University of Medical Sciences , 49 Przybyszewskiego Blvd, 60-355 Poznan, Poland 2 A. Mostowska P. P. Jagodzinski Department of Biochemistry and Molecular Biology, Poznan University of Medical Sciences , 6 S Cytokines, involved in the T-helper 1 system, play a role in the regulation of hepatitis B virus (HBV) clearance and the immune response to HBV antigens during natural infection or planned vaccination. Our aim was to examine whether the polymorphic variants of IL-12 are equally associated with development of antibodies to HBV surface antigen (anti-HBs) in hemodialysis (HD) patients in the case of HBV vaccination or HBV infection. The IL-12A rs568408 and IL-12B rs3212227 polymorphisms were analyzed in relation to anti-HBs development in 602 HD patients with negative antibodies to HBV core antigen (antiHBc) who were hepatitis B vaccinated (group I) as well as in 237 anti-HBc positive HD patients who were infected with HBV in the past (group II). In group I, 199 patients did not develop an anti-HBs titre [10 IU/L (subgroup Ia), whereas in group II, 55 patients did not develop an anti-HBs titre [10 IU/L (subgroup IIa). Patients of groups I and II that developed an anti-HBs [10 IU/L were included into subgroups Ib and IIb, respectively. In hepatitis B vaccinated HD patients, development of a protective anti-HBs titre was positively associated with vintage of renal replacement therapy (RRT), chronic glomerulonephritis as a cause of RRT, and GA rs 568408 IL-12A (OR 1.6, 95 % CI 1.0-2.5, P = 0.035), but a frequency distribution of this genotype between responders and non-responders was not significant when the Bonferroni correction was applied. In HBV infected HD patients, anti-HBs development was positively associated with AC rs3212227 IL-12B (OR 8.0, 95 % CI 2.6-24.9, P \ 0.001), whereas HBsAg positivity, AA rs3212227 IL-12B (OR 0.3, 95 % CI 0.1-0.7, P = 0.007), and CC rs3212227 IL-12B (OR 0.1, 95 % CI 0.03-0.6, P = 0.011) were negative predictors of positive anti-HBs phenotype. When the Bonferroni correction was applied, if appropriate, these associations remained significant. In HD patients, the studied IL-12 polymorphic variants seem to be associated with the anti-HBs phenotype (a) with borderline significance for IL-12A in hepatitis B vaccinated patients, and (b) significantly for IL-12B in patients who underwent natural HBV infection. - Antibodies to the surface antigen of the hepatitis B virus (anti-HBs) are specific neutralizing antibodies indicative of either an immune response triggered as a result of having received a vaccine containing the surface antigen of the hepatitis B virus (HBsAg) or active immunity to the hepatitis B virus (HBV) as a result of prior infection with HBV having HBsAg in its structure. Anti-HBs in the bloodstream may also result from passive immunity created by injection of hepatitis B immunoglobulin for post-exposure prophylaxis. According to the current recommendations, protection of hemodialysis (HD) patients against HBV infection should include hepatitis B vaccination using licensed hepatitis B vaccines given at 0, 1, 2 and 6 months in the dose of 40 lg each administered by the intramuscular route at one site. Patients who did not respond to the primary vaccine series should be revaccinated with three additional doses and retested for response [1]. The development of this advanced vaccination strategy still does not elicit the adequate anti-HBs response in 20 % HD vaccinees [2]. Therefore, a substantial number of HD patients is not adequately protected against HBV infection. Natural HBV transmission to the human body leads to the appearance of specific seromarkers, among them HBsAg, antibodies to HBV core antigen (anti-HBc), and anti-HBs. The development of anti-HBs used to be associated with the disappearance of HBsAg. Anti-HBc are established markers of current (in IgM class) or past (in IgG class) HBV infection. If anti-HBs do not appear during the HBV infection, it results either in HBsAg carrier status, which is associated with detectable HBV deoxyribonucleic acid (DNA) in about 65 % of infected HD patients [3, 4], or in the occurrence of isolated anti-HBc positivity (antiHBc positive individuals are both HBsAg and anti-HBs negative), which in HD patients may be associated with detectable HBV DNA [5]. HBV replication may contribute to morbidity and mortality related to HBV-associated diseases [68]. Ineffective hepatitis B vaccination is predictive for the prevalence and incidence of both HBsAg [9] and anti-HBc [10, 11] positivity. Interleukin (IL)-12 is a heterodimeric proinflammatory cy (...truncated)


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Alicja E. Grzegorzewska, Piotr M. Wobszal, Anna Sowińska, Adrianna Mostowska, Paweł P. Jagodziński. Association of the interleukin-12 polymorphic variants with the development of antibodies to surface antigen of hepatitis B virus in hemodialysis patients in response to vaccination or infection, Molecular Biology Reports, 2013, pp. 6899-6911, Volume 40, Issue 12, DOI: 10.1007/s11033-013-2809-7