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接种乙型肝炎病毒表面抗原疫苗后抗体效价与免疫相关基因变异的关系。一项针对血液透析患者的前瞻性研究。

Titers of antibodies to the surface antigen of hepatitis B virus after vaccination in relation to immunity-related gene variants. A prospective study among hemodialysis patients.

出版信息

Pol Arch Intern Med. 2017 Aug 9;127(7-8):481-489. doi: 10.20452/pamw.4074. Epub 2017 Aug 3.

Abstract

INTRODUCTION    Hemodialysis (HD) patients show a weaker response to hepatitis B virus (HBV) vaccination than the healthy population. Several gene variants were reported to be associated with the levels of antibodies to HBV surface antigen (anti-HBs) after HBV vaccination among healthy individuals. OBJECTIVES    The aim of the study was to determine the effect of immunity-related genes on the maximum anti-HBs antibody levels after vaccination among HD subjects. PATIENTS AND METHODS    This 6-year prospective study included HD patients who were not infected with HBV and underwent HBV vaccination. Before the study, patients were classified as responders (anti-HBs ≥10 IU/l, n = 356) or nonresponders (anti-HBs <10 IU/l, n = 48) to HBV vaccination. Patients were tested for the following gene variants: GC rs7041, rs1155563, rs2298849; RXRA rs10881578, rs10776909, rs749759; VDR rs1544410, rs2228570; IFNL3 rs8099917, rs12979860; IL12A rs568408; IL12B r3212227; IL4R rs1805015; IL13 rs20541; IL18 rs360719; and CCL2 rs1024611. Anti-HBs titers were checked every 6 to 12 months and the individual maximum values were used in the analysis.  RESULTS    There was a significant difference in peak anti-HBs levels between patients with 2 major alleles of IL12A rs568408 (median, 180 IU/l; range, 0-4.105 IU/l) and those carrying 1 or 2 minor alleles (median, 451 IU/l; range, 0-5.342 IU/l; P = 0.004). In a multivariate analysis, a positive correlate of the maximum anti-HBs antibody titers was dialysis duration, while the negative ones included the GG genotype of IL12A rs568408, age, and time elapsed from dialysis onset to peak anti-HBs antibody titers. CONCLUSIONS    In HD patients, peak anti-HBs levels following vaccination are independently associated with the IL12A rs568408 variant.

摘要

简介 血液透析 (HD) 患者对乙型肝炎病毒 (HBV) 疫苗的反应弱于健康人群。据报道,在健康个体中,几种基因变异与 HBV 表面抗原 (抗-HBs) 抗体水平有关。 目的 本研究旨在确定免疫相关基因对 HD 患者接种疫苗后最大抗-HBs 抗体水平的影响。 患者和方法 这是一项为期 6 年的前瞻性研究,纳入了未感染 HBV 且接受 HBV 疫苗接种的 HD 患者。在研究之前,根据 HBV 疫苗接种后的抗-HBs 水平将患者分为应答者(抗-HBs≥10 IU/l,n=356)或无应答者(抗-HBs<10 IU/l,n=48)。检测患者以下基因变异:GC rs7041、rs1155563、rs2298849;RXRA rs10776909、rs10881578、rs749759;VDR rs1544410、rs2228570;IFNL3 rs8099917、rs12979860;IL12A rs568408;IL12B r3212227;IL4R rs1805015;IL13 rs20541;IL18 rs360719;和 CCL2 rs1024611。每 6-12 个月检查一次抗-HBs 滴度,分析个体的最高值。 结果 携带 IL12A rs568408 两个主要等位基因的患者(中位数,180 IU/l;范围,0-4.105 IU/l)与携带 1 个或 2 个次要等位基因的患者(中位数,451 IU/l;范围,0-5.342 IU/l;P=0.004)之间的峰值抗-HBs 水平存在显著差异。多变量分析显示,最大抗-HBs 抗体滴度的正相关因素是透析时间,而负相关因素包括 IL12A rs568408 的 GG 基因型、年龄和从透析开始到峰值抗-HBs 抗体滴度的时间。 结论 在 HD 患者中,接种疫苗后的峰值抗-HBs 水平与 IL12A rs568408 变异独立相关。

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