C4A缺乏与对乙肝疫苗接种无反应

C4A deficiency and nonresponse to hepatitis B vaccination.

作者信息

Höhler Thomas, Stradmann-Bellinghausen Beate, Starke Roland, Sänger Roland, Victor Anja, Rittner Christian, Schneider Peter M

机构信息

I. Department of Internal Medicine, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, Mainz, Germany.

出版信息

J Hepatol. 2002 Sep;37(3):387-92. doi: 10.1016/s0168-8278(02)00205-2.

DOI:10.1016/s0168-8278(02)00205-2

PMID:12175635

Abstract

BACKGROUND/AIMS: Hepatitis B vaccination failure has been linked to the presence of certain human leukocyte antigen class II alleles. However, the functional background of these associations has remained unclear. Complement component C 4 is encoded within the major histocompatibility complex and is essential for classical pathway activation.

METHODS

Healthy individuals (n=4269) were vaccinated in a prospective trial with Engerix B. Nonresponse was classified as anti-HBs<10 U/l after the last vaccination. Seventy-three nonresponders (NR) (1.7%) were identified. For comparison 53 responders (R) (anti-HBs>10 IU/l) were drawn randomly from the same cohort. C4 allotyping was carried out by high-voltage agarose gel electrophoresis and C4alpha-chain typing using sodium dodecyl sulfate-polyacrylamide gel electrophoresis. C4 gene deletions (C4Del) were studied by Southern blot.

RESULTS

C4AQ0 alleles were observed in 45/73 (62%) NR compared to 17/53 (32%) R (P=0.001). C4ADel was observed in 24/73 (33%) NR and in 6/52 (12%) R (P=0.006). C4AQO alleles were present in 21/49 (43%) NR without C4Del compared to 10/46 (22%) in R without C4Del (P=0.031). In a logistic regression with DRB10301, DRB107, DRB11301 and C4AQ0 all except for DRB10301 showed a significant association.

CONCLUSIONS

C4AQ0 shows a DRB1*0301 independent association with vaccine failure. C4AQ0 alleles probably contribute to inefficient complement activation and failure of B cells to secrete anti-HBs.

摘要

背景/目的：乙肝疫苗接种失败与某些人类白细胞抗原II类等位基因的存在有关。然而，这些关联的功能背景仍不清楚。补体成分C4在主要组织相容性复合体内编码，对经典途径激活至关重要。

方法

4269名健康个体参与了一项使用安在时乙肝疫苗的前瞻性试验。无应答被定义为最后一次接种后抗-HBs<10 U/l。共识别出73名无应答者（NR）（1.7%）。为作比较，从同一队列中随机抽取53名应答者（R）（抗-HBs>10 IU/l）。通过高压琼脂糖凝胶电泳进行C4别型分析，使用十二烷基硫酸钠-聚丙烯酰胺凝胶电泳进行C4α链分型。通过Southern印迹研究C4基因缺失（C4Del）。

结果

45/73（62%）的NR中观察到C4AQ0等位基因，而R组中为17/53（32%）（P=0.001）。24/73（33%）的NR中观察到C4ADel，R组中为6/52（12%）（P=0.006）。49名无C4Del的NR中有21/49（43%）存在C4AQ0等位基因，无C4Del的R组中为10/46（22%）（P=0.031）。在包含DRB10301、DRB107、DRB11301和C4AQ0的逻辑回归中，除DRB10301外，其他均显示出显著关联。