一种Toll样受体4（TLR4）基因多态性与瑞典儿童的哮喘及脂多糖诱导的白细胞介素-12（p70）反应降低相关。

A TLR4 polymorphism is associated with asthma and reduced lipopolysaccharide-induced interleukin-12(p70) responses in Swedish children.

作者信息

Fagerås Böttcher Malin, Hmani-Aifa Mounira, Lindström Anna, Jenmalm Maria Christina, Mai Xiao-Mei, Nilsson Lennart, Zdolsek Helena Aniansson, Björkstén Bengt, Söderkvist Peter, Vaarala Outi

机构信息

Division of Pediatrics, Department of Molecular and Clinical Medicine, and Clinical Research Centre, Faculty of Health Sciences, Linköping University, 85 Linköping, Sweden.

出版信息

J Allergy Clin Immunol. 2004 Sep;114(3):561-7. doi: 10.1016/j.jaci.2004.04.050.

DOI:10.1016/j.jaci.2004.04.050

PMID:15356557

Abstract

BACKGROUND

Bacterial signals play an important role in the maturation of the immune system. Polymorphisms in genes coding for receptors to bacterial components can alter the immune responsiveness of the host to microbial agents and may indicate the development of aberrant immune responses that are associated with immune-mediated diseases such as atopic diseases.

OBJECTIVE

The study's objective was to investigate the relationship between TLR4 and CD14 gene polymorphisms, the LPS responsiveness of PBMCs, and the presence of asthma and allergic rhinoconjunctivitis in children.

METHODS

The TLR4 (Asp299Gly) and CD14/-159 polymorphisms were determined in 115 Swedish children aged 8 and 14 years. LPS-induced IL-12(p70), IL-10, and IFN-gamma responses of PBMCs from 69 of the children were analyzed by means of ELISA. The levels of soluble CD14 in serum samples were analyzed by means of ELISA, and the total IgE levels were analyzed by means of UniCAP Total IgE (Pharmacia Diagnostics, Uppsala, Sweden).

RESULTS

Decreased LPS-induced IL-12(p70) and IL-10 responses were associated with the TLR4 (Asp299Gly) polymorphism and independently with asthma, especially atopic asthma. The TLR4 (Asp299Gly) polymorphism was associated with a 4-fold higher prevalence of asthma in school-aged children (adjusted odds ratio 4.5, 95% CI 1.1-17.4) but not to allergic rhinoconjunctivitis.

CONCLUSION

A TLR4 polymorphism modifies innate immune responses in children and may be an important determinant for the development of asthma. This may influence the outcome of intervention studies that use microbial stimuli as immune modulators.

摘要

背景

细菌信号在免疫系统成熟过程中发挥重要作用。编码细菌成分受体的基因多态性可改变宿主对微生物制剂的免疫反应性，并可能预示与免疫介导疾病（如特应性疾病）相关的异常免疫反应的发生。

目的

本研究旨在探讨TLR4和CD14基因多态性、外周血单个核细胞（PBMC）对脂多糖（LPS）的反应性与儿童哮喘及变应性鼻结膜炎之间的关系。

方法

对115名8岁和14岁的瑞典儿童进行TLR4（Asp299Gly）和CD14 / -159多态性检测。采用酶联免疫吸附测定（ELISA）法分析69名儿童PBMC经LPS诱导后的白细胞介素-12（p70）、白细胞介素-10和γ-干扰素反应。采用ELISA法分析血清样本中可溶性CD14水平，采用UniCAP总IgE（瑞典乌普萨拉法玛西亚诊断公司）分析总IgE水平。