AUTHOR=Yao Yufeng , Yang Huijuan , Shi Lei , Liu Shuyuan , Li Chuanying , Chen Jun , Zhou Ziyun , Sun Mingbo , Shi Li 

TITLE=HLA Class II Genes HLA-DRB1, HLA-DPB1, and HLA-DQB1 Are Associated With the Antibody Response to Inactivated Japanese Encephalitis Vaccine

JOURNAL=Frontiers in Immunology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2019.00428

DOI=10.3389/fimmu.2019.00428

ISSN=1664-3224

ABSTRACT=<p><bold>Aim:</bold> The objective of this study was to evaluate the association of the human leukocyte antigen (HLA) class II genes <italic>HLA-DRB1, HLA-DPB1</italic>, and <italic>HLA-DQB1</italic> with the humoral immune response elicited by inactivated Japanese encephalitis (JE) vaccine (IJEV).</p><p><bold>Methods:</bold> A total of 373 individuals aged 3–12 years in the Inner Mongolia Autonomous Region in China, who received two doses of IJEV at 0 and 7 days, were enrolled in the current study. Based on the individuals' specific JE virus (JEV)-neutralizing antibodies (NAbs), they were divided into a seropositive and a seronegative group. <italic>HLA-DRB1, HLA-DPB1</italic>, and <italic>HLA-DQB1</italic> were genotyped using a sequencing-based typing method. Next, the association of the HLA class II genes and their haplotypes with antibody response was evaluated.</p><p><bold>Results:</bold> Based on NAbs, a total of 161 individuals were classified as seropositive and 212 as seronegative. <italic>DQB1</italic><sup>*</sup><italic>02:01</italic> was significantly associated with JEV seropositivity (<italic>P</italic> &lt; 0.001, OR = 0.364, 95% CI: 0.221–0.600), while <italic>DQB1</italic><sup>*</sup><italic>02:02</italic> was significantly associated with JEV seronegativity (<italic>P</italic> = 5.03 × 10<sup>−6</sup>, OR = 7.341, 95% CI: 2.876–18.736). The haplotypes <italic>DRB1</italic><sup>*</sup><italic>07:01-DPB1</italic><sup>*</sup><italic>04:01-DQB1</italic><sup>*</sup><italic>02:01, DRB1</italic><sup>*</sup><italic>15:01-DPB1</italic><sup>*</sup><italic>02:01-DQB1</italic><sup>*</sup><italic>06:02, DRB1</italic><sup>*</sup><italic>07:01-DQB1</italic><sup>*</sup><italic>02:01</italic>, and <italic>DPB1</italic><sup>*</sup><italic>02:01-DQB1</italic><sup>*</sup><italic>06:02</italic> were very frequent in the seropositive group, while <italic>DRB1</italic><sup>*</sup><italic>07:01-DPB1</italic><sup>*</sup><italic>17:01-DQB1</italic><sup>*</sup><italic>02:02, DRB1</italic><sup>*</sup><italic>07:01-DQB1</italic><sup>*</sup><italic>02:02</italic>, and <italic>DPB1</italic><sup>*</sup><italic>17:01-DQB1</italic><sup>*</sup><italic>02:02</italic> were very frequent in the seronegative group. The presence of <italic>DRB1</italic><sup>*</sup><italic>01:01, DRB1</italic><sup>*</sup><italic>04:05, DRB1</italic><sup>*</sup><italic>09:01, DRB1</italic><sup>*</sup><italic>12:02, DRB1</italic><sup>*</sup><italic>13:02</italic>, and <italic>DRB1</italic><sup>*</sup><italic>14:01</italic> was associated with a higher geometric mean titer (GMT) of NAbs than that of <italic>DRB1</italic><sup>*</sup><italic>11:01</italic> at the <italic>DRB1</italic> locus (<italic>P</italic> &lt; 0.05). At the <italic>DPB1</italic> locus, the presence of <italic>DPB1</italic><sup>*</sup><italic>05:01</italic> was associated with higher GMTs than that of <italic>DPB1</italic><sup>*</sup><italic>02:01</italic> and <italic>DPB1</italic><sup>*</sup><italic>13:01</italic> (<italic>P</italic> &lt; 0.05), and the presence of <italic>DPB1</italic><sup>*</sup><italic>04:01</italic> and <italic>DPB1</italic><sup>*</sup><italic>09:01</italic> was associated with higher GMTs than that of <italic>DPB1</italic><sup>*</sup><italic>13:01</italic> (<italic>P</italic> &lt; 0.05).</p><p><bold>Conclusions:</bold> The present study suggests that HLA class II genes may influence the antibody response to IJEV.</p>