Berghöfer B, Frommer T, König I R, Ziegler A, Chakraborty T, Bein G, Hackstein H
Institute for Clinical Immunology and Transfusion Medicine, Justus-Liebig University, Langhansstrasse 7, D-35392 Giessen, Germany.
Clin Exp Allergy. 2005 Sep;35(9):1147-54. doi: 10.1111/j.1365-2222.2005.02325.x.
Toll-like receptor 9 (TLR9) is a pattern-recognition receptor that detects unmethylated CpG motifs prevalent in bacterial and viral DNA. TLR9 stimulation is a key event after bacterial infection, triggering innate immunity and T-helper type 1 skewed adaptive immunity. Synthetic CpG-oligodeoxynucleotides (CpG-ODNs) represent a promising and novel class of immune adjuvants for allergy treatment, vaccination, and cancer therapy. However, common functional TLR9 gene variants could interfere with the clinical utilization of CpG-ODN in immunotherapy. Recently, a possible association of TLR9 polymorphism C-1237T with asthma has been reported.
The aim of the present study was to investigate whether TLR9 polymorphisms or haplotypes have functional relevance and are associated with atopy.
We genotyped five common TLR9 single-nucleotide polymorphisms (SNPs) in promoter, exon, and intron regions of the gene in 527 healthy blood donors, and estimated four common haplotypes. The total IgE and specific IgE levels against the most common aeroallergens were measured (n=303). IFN-alpha production by plasmacytoid dendritic cells (pDCs) was analysed after stimulation with TLR9 ligand CpG-ODN (n=220).
No significant influence of common TLR9 polymorphisms and haplotypes on the total and specific IgE levels was found. Functional analysis of CpG-ODN-induced IFN-alpha did not indicate a significant role for common TLR9 gene polymorphisms in TLR9 function.
We conclude that common genetic differences in the TLR9 gene exert no major influence on allergy susceptibility, and are unlikely to have on impact on clinical application of CpG-ODNs.
Toll样受体9（TLR9）是一种模式识别受体，可检测细菌和病毒DNA中普遍存在的未甲基化CpG基序。TLR9刺激是细菌感染后的关键事件，可触发先天免疫和1型辅助性T细胞偏向的适应性免疫。合成的CpG寡脱氧核苷酸（CpG-ODN）是一类有前途的新型免疫佐剂，可用于过敏治疗、疫苗接种和癌症治疗。然而，常见的功能性TLR9基因变异可能会干扰CpG-ODN在免疫治疗中的临床应用。最近，有报道称TLR9基因多态性C-1237T与哮喘可能存在关联。
本研究旨在调查TLR9基因多态性或单倍型是否具有功能相关性以及是否与特应性相关。
我们对527名健康献血者的该基因启动子、外显子和内含子区域的五个常见TLR9单核苷酸多态性（SNP）进行了基因分型，并估计了四种常见单倍型。测量了针对最常见气传变应原的总IgE和特异性IgE水平（n = 303）。在用TLR9配体CpG-ODN刺激后，分析浆细胞样树突状细胞（pDC）产生的IFN-α（n = 220）。
未发现常见的TLR9基因多态性和单倍型对总IgE和特异性IgE水平有显著影响。对CpG-ODN诱导的IFN-α的功能分析未表明常见的TLR9基因多态性在TLR9功能中起显著作用。
我们得出结论，TLR9基因的常见遗传差异对过敏易感性没有重大影响，并且不太可能对CpG-ODN的临床应用产生影响。
