Effects of cytokine and cytokine receptor gene variation on high anti-HB titers: following up on Taiwan's neonatal hepatitis B immunization program

Abstract

Background: A significant percentage of Taiwanese neonatal HB immunization recipients have subsequently exhibited low anti-HB titers at non-protective or undetectable levels. Several mechanisms have been proposed to explain this phenomenon, including low vaccination responsiveness, deficient lymphocyte function, inappropriate antigen processing and presentation, and abnormal cytokine secretion.

Methods: To determine genetic influences resulting in high anti-HB titers, we divided a study cohort of 183 individuals into an anti-HBs≥1000 mIU/mL group and a 10-1000 mIU/mL anti-HBs titer group. Chi-square tests were used to compare genotype and allelic frequencies between the two groups.

Results: Data from univariate and multivariate regression analyses of cytokine and cytokine receptor gene variants indicate (a) increased potential of high anti-HB titers in the presence of the TT genotype of the IL-4 rs2243250 SNP (OR=3.19; p=0.012) and the AA genotype of the IL-4R rs1805010 SNP (OR=2.25; p=0.048), and (b) individuals carrying the TT genotype of the IL-4 rs2243250 SNP had anti-HB titers at levels that were almost twice as high as those in individuals carrying the CC genotype (478.8 mIU/mL and 290.3 mIU/mL, respectively; p=0.033).

Conclusion: Genetic determinants, especially IL-4 and IL-4R, may contribute to high anti-HB titers in immune responses to HB vaccinations.