Department of Epidemiology, Colorado School of Public Health, Aurora, CO, United States.
Vaccine. 2013 Feb 4;31(7):1123-8. doi: 10.1016/j.vaccine.2012.12.026. Epub 2012 Dec 20.
The primary prevention measure for influenza infection has been the use of influenza vaccines. However, even when the vaccine and circulating strains are well-matched, some healthy children do not respond to the vaccine, likely due to a genetic basis for immune hyporesponsiveness. The primary objective of this study was to identify HLA class II genes associated with clinical hyporesponsiveness after trivalent inactivated influenza vaccine (TIV) in children.
We conducted a case-control study nested within a retrospective cohort of children that were screened at birth for HLA-DR,DQ genotypes by the Diabetes Autoimmunity Study in the Young (DAISY) and were subsequently followed for up to 8 years by Kaiser Permanente, Colorado (KPCO). Hyporesponsiveness was clinically defined as the occurrence of influenza or influenza-like illness (ILI) in peak influenza weeks in children fully vaccinated with TIV. Each child with clinical hyporesponse (n=252) was matched to 4 randomly selected controls (n=1006) by age and season. Children with clinical hyporesponse to TIV were identified using the Kaiser electronic clinical and immunization databases. Fully vaccinated children within the KPCO-DAISY cohort who did not have a diagnosis of ILI during the entire influenza season were eligible to be controls for that season. Class II HLA-DRB1 and HLA-DQB1 genes were the primary exposure variables. We used conditional logistic regression to calculate the matched odds ratios.
In non-Hispanic white children, HLA-DR7/4,DQB1 0302 genotype was significantly associated (OR=5.15; 95% CI=1.94, 13.67; p=0.001), while in Hispanic children, HLA-DRB1 15 or 16 allele (OR=0.31; 95% CI=0.14, 0.69; p=0.004) and HLA-DR7/Y (DRB1 11, DRB1 13 and DRB1 14) genotype (OR=5.84; 95% CI=1.68, 20.28; p=0.006) were significantly associated with clinical hyporesponsiveness after TIV.
HLA class II genes are associated with clinical hyporesponsiveness to TIV. This finding is important as it may help identify a group of children who are not protected by the commonly used TIV and may require alternative preventive strategies.
流感感染的主要预防措施是使用流感疫苗。然而，即使疫苗与流行株匹配良好，一些健康儿童对疫苗也没有反应，这可能是由于免疫低反应性的遗传基础。本研究的主要目的是确定与儿童接种三价灭活流感疫苗（TIV）后临床低反应性相关的 HLA Ⅱ类基因。
我们进行了一项病例对照研究，该研究嵌套在一个回顾性队列研究中，该队列在出生时通过糖尿病自身免疫研究中的年轻人（DAISY）筛查 HLA-DR、DQ 基因型，随后由科罗拉多州的 Kaiser Permanente（KPCO）进行长达 8 年的随访。低反应性通过临床定义为在 TIV 完全接种的儿童中，在流感高峰期发生流感或流感样疾病（ILI）。在 TIV 临床低反应性的 252 名儿童中，按年龄和季节与 4 名随机选择的对照者（1006 名）进行匹配。在 Kaiser 电子临床和免疫数据库中识别出 TIV 临床低反应性的儿童。在 KPCO-DAISY 队列中，整个流感季节未诊断为 ILI 的完全接种疫苗的儿童有资格成为该季节的对照者。Ⅱ类 HLA-DRB1 和 HLA-DQB1 基因是主要的暴露变量。我们使用条件逻辑回归计算匹配的比值比。
在非西班牙裔白人儿童中，HLA-DR7/4、DQB1 0302 基因型与临床低反应性显著相关（OR=5.15；95%CI=1.94，13.67；p=0.001），而在西班牙裔儿童中，HLA-DRB1 15 或 16 等位基因（OR=0.31；95%CI=0.14，0.69；p=0.004）和 HLA-DR7/Y（DRB1 11、DRB1 13 和 DRB1 14）基因型（OR=5.84；95%CI=1.68，20.28；p=0.006）与 TIV 后临床低反应性显著相关。
HLA Ⅱ类基因与 TIV 的临床低反应性相关。这一发现很重要，因为它可以帮助识别一组未受常用 TIV 保护的儿童，他们可能需要替代预防策略。
