Zitnik Simona Eva, Rüschendorf Franz, Müller Sebastian, Sengler Claudia, Lee Young-Ae, Griffioen Rupino W, Meglio Paolo, Wahn Ulrich, Witt Heiko, Nickel Renate
Department of Pediatric Pneumology and Immunology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Pediatr Allergy Immunol. 2009 Sep;20(6):551-5. doi: 10.1111/j.1399-3038.2008.00815.x. Epub 2009 Jun 10.
Increased total and specific serum immunoglobulin E (IgE) levels are common characteristics of atopic diseases and their basal production is proposed to be under strong genetic control. Interleukin 13 (IL13) variants have been consistently associated with total serum IgE levels in white populations with a strongest association in non-atopics. The aim of this study was to test the IL13 p.R130Q and c.1-1111C>T variants in children with atopic dermatitis (AD) for associations with total serum IgE and early sensitization to common food and inhalant allergens and with asthma. We included 453 children with AD [participants of the Early Treatment of the Atopic Child (ETAC) study] that were followed from the age of 12-24 months for 3 yr. Total and specific IgE were determined at four time points. We genotyped the IL13 p.R130Q and c.1-1111C>T variants by melting curve analysis. In children up to 4 yr of age, the 130Q allele was related to slightly higher total IgE levels compared to heterozygotes and 130R homozygotes. More importantly, both IL13 variants were significantly associated with sensitization to food allergens, with most significant results for sensitization to egg (p = 0.0001). Although early sensitization to hen's egg represents a strong risk factor for subsequent sensitization to inhalant allergens and asthma, the investigated IL13 variants were not associated with these phenotypes at the age of 48-60 months. In summary IL13 variants contribute to elevated levels of total serum IgE in young atopic children and are strongly associated with sensitization to food allergens, particularly to hen's egg. These findings suggest that IL13 variants play a major role not only in non-cognate but also in allergen specific IgE synthesis.
血清总免疫球蛋白E（IgE）水平和特异性IgE水平升高是特应性疾病的常见特征，其基础产生被认为受强大的基因控制。白细胞介素13（IL13）变体一直与白种人群的血清总IgE水平相关，在非特应性人群中关联最强。本研究的目的是检测特应性皮炎（AD）患儿中IL13 p.R130Q和c.1-1111C>T变体与血清总IgE、对常见食物和吸入性过敏原的早期致敏以及哮喘之间的关联。我们纳入了453名AD患儿[特应性儿童早期治疗（ETAC）研究的参与者]，从12至24个月龄开始随访3年。在四个时间点测定总IgE和特异性IgE。我们通过熔解曲线分析对IL13 p.R130Q和c.1-1111C>T变体进行基因分型。在4岁以下儿童中，与杂合子和130R纯合子相比，130Q等位基因与略高的总IgE水平相关。更重要的是，两种IL13变体均与食物过敏原致敏显著相关，对鸡蛋致敏的结果最为显著（p = 0.0001）。尽管对鸡蛋的早期致敏是随后对吸入性过敏原致敏和哮喘的强烈危险因素，但在48至60个月龄时，所研究的IL13变体与这些表型无关。总之，IL13变体导致幼年特应性儿童血清总IgE水平升高，并与食物过敏原致敏密切相关，尤其是对鸡蛋的致敏。这些发现表明，IL13变体不仅在非同源IgE合成中起主要作用，而且在过敏原特异性IgE合成中也起主要作用。
