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,Adrianna Mostowska,Anna Sowińska,Paweł P Jagodziński,Piotr M Wobszal

doi:10.1007/s11033-013-2809-7

Alicja E Grzegorzewska, Adrianna Mostowska + Show 3 more

Open Access

https://doi.org/10.1007/s11033-013-2809-7

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Abstract

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.

Highlights

Antibodies to the surface antigen of the hepatitis B virus 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
In the logistic regressions that included gender, age, renal replacement therapy (RRT) vintage, kidney diseases, liver enzymes, anti-hepatitis C virus (HCV), and polymorphic variants of IL-12A, there was a positive association of anti-HBs development in response to hepatitis B vaccination with concurrently RRT vintage, chronic glomerulonephritis, and GA IL-12A; a negative association was shown with age (P \ 0.001 for the significance of this model)
Our study suggests that cytokine gene polymorphisms associated with a positive anti-HBs phenotype may be different in the case of vaccination than those shown in the case of HBV infection

Summary

Introduction

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. 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]. A substantial number of HD patients is not adequately protected against HBV infection

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