The Association Between HLA-DRB*15 Alleles And Expression Of Th1/Th2 Cytokines In The Immune Response To Hepatitis B Vaccine

Objective:To investigate HLA-DRB*15 alleles and the expression of Th1/Th2 cytokines in the immune response to hepatitis B vaccine,and elucidate the effect on the hepatitis B vaccine about the relationship between HLA-DRB1*15 alleles and Th1/Th2 cytokine IFN-γ,IL-4,to realize the underlying immunogenetic mechanism of hepatitis B vaccine failure.Methods:935 healthy college students aged 21 to 24 year old from Han nationality of Guangxi province,who had received standard courses of vaccination with recombinant hepatitis B virus vaccine at month 0,1 and 6 soon after they had been admitted into the college,were tested HBV makers(HBsAg, anti-HBs,anti-HBc) and liver function.According to the dfferent immune effect, 80 vaccinees of non-or-hypor-responders(anti-HBs S/N＜10) and 62 vaccinees of medium or hyper-responders(anti-HBs S/N＞10) were for the subjects.All of the vaccinees were with mormal liver function and negative HBV makers. Detection of HLA-DRB1*15 was performed by polymerase chain reaction using sequence specific primer(PCR-SSP),and IFN-γ,IL-4 cytokines correlating to Th1/Th2 were by the double antibody sandwich enzyme linked immununo- sorbent assay(ELISA).Resulsts:①The allelic frequencies of HLA-DRB1*15 is much lower in the non-or hypor-responders than that in medium or hyper-responders(11.25%vs 36.67%,P=0.001);②The mean concentration of IFN-γin the non-or-hyporresponders (6.28±6.84 pg/ml) was much less than that of medium or hyperresponders (16.28±10.05pg/ml) to hepatitis B vaccination(P=0.000);③The mean concentration of IL-4 in the non-or-hyporresponders(2.36±1.91 pg/ml) was much less than that of medium or hyper-responders(8.50±6.68 pg/ml) to hepatitis B vaccination(P=0.000);④The mean concentration of IFN-γin HLA-DRB1*15 negative subjects(9.76±9.54 pg/ml) was less than of HLA-DRB1*15 positive subjects(13.82±9.89 pg/ml)(P=0.029);⑤The mean concentration of IL-4 in the HLA-DRB1*15 negative(4.82±5.84 pg/ml)and the positive subjects(5.81±4.27 pg/ml)(P=0.029) showed no significant differences between the two groups(P=0.207)Conclusions:①HLA-DRB1*15 might be the gene enhanced the immune effect of hepatitis B vaccination in the population from Guangxi province;②The levels of cytokines IFN-γand IL-4 correlating to Th1/Th2 cells might affect on the immune effect of hepatitis B vaccination;③HLA-DRB1*15 might be related to affect the level of cytokines IFN-γcorrelating to Th1 cells to enhance the immune response to hepatitis B vaccine;④HLA-DRB1*15 mightn't be related to affect the level of cytokines IL-4 correlating to Th2 cells to enhanc the immune response of hepatitis B vaccine.