Marschan Emma, Honkanen Jarno, Kukkonen Kaarina, Kuitunen Mikael, Savilahti Erkki, Vaarala Outi
The Hospital for Children and Adolescents, University of Helsinki, Helsinki, Finland.
Pediatr Allergy Immunol. 2008 Mar;19(2):132-9. doi: 10.1111/j.1399-3038.2007.00593.x. Epub 2007 Jul 25.
Risk of allergic diseases has been linked to abnormal patterns of fetal immune development, suggesting that priming of the immune system may occur in utero. The aim of the study was to investigate whether the pattern of immune response in cord blood mononuclear cells (CBMC) shows association with allergic diseases and IgE sensitization at 2 yr of age, and to study the effect of maternal probiotic supplementation on CBMC immune responses. CBMC were isolated from 98 neonates in a randomized double-blinded intervention study. CBMC were stimulated with beta-lactoglobulin, and phytohemaglutinin (PHA). Secretion of interferon-gamma (IFN-gamma), interleukin-5 (IL-5), and IL-13 was measured by an ELISA; IL-2, IL-4, and IL-10 by a cytokine bead assay. T-cell polarization-associated IL-4 receptor and IL-12R expressions, and the respective transcription factors GATA-3 and T-bet were analyzed with RT-PCR. The above responses were compared with the development of allergic diseases and IgE sensitization at 2 yr of age, and with the maternal probiotic or placebo supplementation. PHA-stimulated GATA-3 expression and IL-2 secretion in CBMC were higher in IgE-sensitized children at an age of 2 yr than in the non-sensitized, non-allergic children (p = 0.03 and 0.026). PHA-induced expression of GATA-3 correlated with IL-5 (p = 0.003, r = 0.300) and IL-13 (p = 0.007, r = 0.278) secretion of CBMC, and IL-5 secretion of beta-lactoglobulin-stimulated CBMC was higher in IgE-sensitized children at 2 yr of age than in the non-sensitized, non-allergic children (p = 0.013). Probiotic bacteria had no effect on CBMC immune responses. In CBMC-enhanced induction of GATA-3, which activates several Th2 cytokines genes, was a risk factor for IgE sensitization. The immune deviation towards Th2-type immunity developed already in utero and seemed to modulate the pattern of immune response favoring an IgE response to environmental antigens.
过敏性疾病的风险与胎儿免疫发育的异常模式有关，这表明免疫系统的致敏可能在子宫内就已发生。本研究的目的是调查脐带血单个核细胞（CBMC）中的免疫反应模式是否与2岁时的过敏性疾病和IgE致敏相关，并研究母体补充益生菌对CBMC免疫反应的影响。在一项随机双盲干预研究中，从98名新生儿中分离出CBMC。用β-乳球蛋白和植物血凝素（PHA）刺激CBMC。通过酶联免疫吸附测定法（ELISA）测量干扰素-γ（IFN-γ）、白细胞介素-5（IL-5）和IL-13的分泌；通过细胞因子微珠检测法测量IL-2、IL-4和IL-10。用逆转录聚合酶链反应（RT-PCR）分析T细胞极化相关的IL-4受体和IL-12R表达以及各自的转录因子GATA-3和T-bet。将上述反应与2岁时过敏性疾病和IgE致敏的发展情况以及母体补充益生菌或安慰剂的情况进行比较。在2岁的IgE致敏儿童中，PHA刺激的CBMC中GATA-3表达和IL-2分泌高于未致敏、无过敏的儿童（p = 0.03和0.026）。PHA诱导的GATA-3表达与CBMC的IL-5（p = 0.003，r = 0.300）和IL-13（p = 0.007，r = 0.278）分泌相关，并且在2岁的IgE致敏儿童中，β-乳球蛋白刺激的CBMC的IL-5分泌高于未致敏、无过敏的儿童（p = 0.013）。益生菌对CBMC免疫反应没有影响。在CBMC中，增强诱导激活多种Th2细胞因子基因的GATA-3是IgE致敏的一个危险因素。向Th2型免疫的免疫偏差在子宫内就已出现，并且似乎调节了有利于对环境抗原产生IgE反应的免疫反应模式。
