Jackola Duaine R, Basu Saonli, Liebeler Carol L, Willaert Rebecca, Luah San-San, Oetting William, King Richard A, Blumenthal Malcolm N
The Asthma and Allergy Program, Division of Pulmonary, Allergy and Critical Care Medicine, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
Int Arch Allergy Immunol. 2006;139(3):217-24. doi: 10.1159/000091167. Epub 2006 Jan 27.
CD14 promoter DNA sequence polymorphisms for the endotoxin receptor gene have been implicated in modulating allergen-specific immunoglobulin (Ig)E responses in randomly selected individuals with atopy. We sought to determine if a single nucleotide polymorphism in the CD14 promoter region is associated with atopy in atopic families, and to assess its influence on serum levels of CD14 and allergen-specific IgE and IgG1 responses.
We screened 367 members of 91 Caucasian nuclear families with a history of asthma for pulmonary function by spirometry, including methacholine challenge to detect bronchial hyperreactivity, and atopy by serum total IgE and skin prick test to 14 allergens. The CD14 promoter single nucleotide polymorphism was analyzed in DNA isolated from peripheral blood mononuclear cells to identify C/C, C/T and T/T genotypes. Serum tests were done for soluble CD14 (sCD14) and dust mite-specific antibody (Der p 1-IgG1).
Serum sCD14 levels were not associated with clinical phenotypes (asthma, bronchial hyperreactivity or atopy). However, sCD14 levels were inversely related to both allergen-specific IgE and Der p 1-IgG1 production, but only among those with evidence of atopic sensitization. Linear regression analysis, accounting for random family effects, demonstrated a higher production of allergen-specific IgE or Der p 1-IgG1 associated with the T/T genotype and a lower level of specific IgE and IgG1 production associated with sCD14 levels.
An element of the innate immune system (CD14) has profound effects upon modulating the acquired allergen-specific immunoglobulin responses among those with an inherited atopic predisposition.
内毒素受体基因的CD14启动子DNA序列多态性与随机选择的特应性个体中变应原特异性免疫球蛋白（Ig）E反应的调节有关。我们试图确定CD14启动子区域的单核苷酸多态性是否与特应性家族中的特应性相关，并评估其对血清CD14水平以及变应原特异性IgE和IgG1反应的影响。
我们对91个有哮喘病史的白种人核心家庭的367名成员进行了肺功能筛查，采用肺活量测定法，包括乙酰甲胆碱激发试验以检测支气管高反应性，并通过血清总IgE和对14种变应原的皮肤点刺试验检测特应性。对从外周血单个核细胞中分离的DNA进行CD14启动子单核苷酸多态性分析，以鉴定C/C、C/T和T/T基因型。进行血清检测以测定可溶性CD14（sCD14）和尘螨特异性抗体（Der p 1-IgG1）。
血清sCD14水平与临床表型（哮喘、支气管高反应性或特应性）无关。然而，sCD14水平与变应原特异性IgE和Der p 1-IgG1的产生呈负相关，但仅在有特应性致敏证据的个体中如此。考虑到随机家庭效应的线性回归分析表明，T/T基因型与变应原特异性IgE或Der p 1-IgG1的产生较高相关，而特异性IgE和IgG1的产生水平较低与sCD14水平相关。
先天免疫系统的一个成分（CD14）对调节具有遗传特应性易感性个体的获得性变应原特异性免疫球蛋白反应具有深远影响。
