成人乙型肝炎疫苗接种后无应答的影响因素及与外周血滤泡T细胞的关联研究

Influencing factors of non-response after adult hepatitis B vaccination and its relationship with peripheral blood follicular T cells

摘要:

目的 分析成人乙型肝炎（乙肝）疫苗接种后无应答的影响因素，及与外周滤泡T细胞的关联。方法 回顾性分析2022年1月至2022年12月至信阳市平桥区疾病预防控制中心接受乙肝疫苗接种的129例患者的临床资料，依据接种后乙型肝炎病毒表面抗体（HBsAb）水平，将接种后HBsAb≥10 mIU/mL的100例患者列为应答组，将接种后HBsAb<10 mIU/mL的29例患者列为无应答组。收集、对比两组患者的一般资料及临床资料，经统计学单因素分析、Logistic多因素回归分析归纳可导致成人乙肝疫苗接种后无应答的影响因素。比较两组患者外周血滤泡T细胞间的差异，经Spearman相关性系数检验外周血滤泡T细胞与乙肝疫苗接种后无应答的关联。结果 统计学单因素分析结果显示，无应答组内男性、年龄≥60岁、体重指数（BMI）≥24 kg/m²、有吸烟饮酒史、肌肉注射、按10 μg 0-1-6月程序接种、有造血干细胞移植治疗史、合并人类免疫缺陷病毒（HIV）感染、Toll样受体（TLRs）高表达、外周血滤泡辅助性T细胞（Tfh）低表达、白细胞介素-12（IL-12）低表达、外周血滤泡调节性T细胞（Tfr）高表达、趋化因子受体5（CXCR5）高表达占比均高于应答组（P<0.05）。Logistic多因素回归分析结果显示，肌肉注射、按10 μg 0-1-6月程序接种、Tfh低表达、IL-12低表达、Tfr高表达、CXCR5高表达为成人乙肝疫苗接种后无应答的主要影响因素。无应答组的Tfh、IL-12分别为（17.44±3.25）%、（70.33±10.21）ng/mL，均低于应答组［（19.25±3.16）%、（75.45±10.23）ng/mL］；Tfr、CXCR5分别为（7.32±1.41）%、（33.49±5.18）ng/mL，均高于应答组［（6.65±1.24）%、（30.23±5.22）ng/mL］，P<0.05。经Spearman相关性系数检验，Tfh、IL-12与HBsAb应答水平呈正相关，Tfr、CXCR5与HBsAb应答水平呈负相关。结论 乙肝疫苗接种方式、程序不当以及个人免疫功能紊乱均是导致成人乙肝疫苗接种后无应答或应答低的重要因素。Tfh、IL-12与HBsAb应答水平呈正相关，Tfr、CXCR5与HBsAb应答水平呈负相关。

Abstract:

Objective To analyze the influencing factors of non-response after adult hepatitis B vaccination, and the relationship between non-response and peripheral follicular T cells.Methods Retrospective analysis was made on the clinical data of 129 patients who received hepatitis B vaccination from January 2022 to December 2022 in our hospital. According to the level of HBsAb after vaccination, 100 patients with HBsAb ≥10 mIU/mL after vaccination were listed as the response group, and 29 patients with HBsAb <10 mIU/mL after vaccination were listed as the non-response group. The general data and clinical data of patients in the two groups were collected and compared. Statistical single factor analysis and logistic multi-factor regression analysis summarized the influencing factors that can lead to non-response of adults after hepatitis B vaccination. The difference between peripheral blood follicular T cells of the two groups was compared, and the correlation between peripheral blood follicular T cells and non -response after hepatitis B vaccination was tested by Spearman correlation coefficient.Results The results of statistical univariate analysis showed that the proportion of male, aged ≥60 years old, BMI ≥24 kg/m², had a history of smoking and drinking, received intramuscular injections, received 10 μg 0-1-6 months program vaccination, had a history of hematopoietic stem cell transplantation treatment, combined with HIV infection, high expression of TLRs, low expression of Tfh, low expression of IL-12, high expression of Tfr, and high expression of CXCR5 in the non-response group were higher than those in the response group (P<0.05). The results of logistic multiple regression analysis showed that intramuscular injection, 10 μg 0-1-6 months program vaccination, low expression of Tfh, low expression of IL-12, high expression of Tfr, and high expression of CXCR5 were the main influencing factors of adult hepatitis B non-response after vaccination. The Tfh and IL-12 levels in the non-responsise group were 17.44%±3.25% and 70.33±10.21 ng/mL, lower than the response group (19.25%±3.16% and 75.45±10.23 ng/mL); Tfr and CXCR5 were 7.32%±1.41% and 33.49±5.18 ng/mL, higher than the response group (6.65%±1.24% and 30.23±5.22 ng/mL), P<0.05. According to Spearman correlation coefficient test, Tfh, IL-12 are positively correlated with HBsAb response levels, while Tfr, CXCR5 are negatively correlated with HBsAb response levels.Conclusion Improper hepatitis B vaccination methods, procedures and personal immune dysfunction are important factors that lead to no response or low response after hepatitis B vaccination in adults. Tfh, IL-12 are positively correlated with HBsAb response levels, while Tfr, CXCR5 are negatively correlated with HBsAb response levels.