Association of HLA-DR14-DR52 with low responsiveness to hepatitis B vaccine in Chinese residents in Taiwan

To determine the HLA-linked immune response gene that controls low responsiveness to hepatitis B surface antigen (HBsAg), HLA typing was performed in 33 initial non-responders (male:female = 23:10, age 1.5-46 years) who had poor antibody response (anti-HBs < 10 mIU ml^-1) after four doses of plasma-derived hepatitis B vaccine. Of 33 initial non-responders, 26 received two additional doses of either the same vaccine (n = 18) or recombinant hepatitis B vaccine (n = 8) and returned for anti-HBs measurement. At 1 month after the sixth dose, anti-HBs was still <10 mIU ml^-1 in 20 cases and 10-20 mIU ml^-1 in three cases. Analysis of HLA antigen frequencies in these 23 ultimate low responders revealed that nine (39%) were positive for DR14, a statistically significant association of low responsiveness to hepatitis B vaccine with HLA-DR14. In addition, 26% of the ultimate low-responders were positive for DQ3, a frequency significantly lower than the expected rate in the general population. Among the nine ultimate low-responders with DR14, seven were heterozygous for this allele, while the other two cases had a single isolated DR14; and all nine were in association with DR52. These results suggest that a DR14-DR52 association, probably dominantly expressed, may be involved in the low immune responsiveness to hepatitis B vaccine of the Chinese population in Taiwan.