台灣氣喘孩童血液中乙型制動素-2濃度高低與氣喘嚴重度及其臨床表徵之關聯性

介紹氣喘的盛行率在這十幾年不管兒童或成人都有迅速增加。 β arrestin 2，最初發現可以結合並去敏化G蛋白偶聯β2-腎上腺素能受體（β2-AR），β2-AR最近被認為是一種多功能適配器/支架蛋白，可以動態組裝廣泛的多蛋白複合物。此外，β-arrestin 2基因剔除動物已被發現比較不能被誘發過敏性氣喘（氣道高反應性）。我們進行這項研究調查台灣過敏兒童在周邊血液單核細胞β-arrestin2濃度和氣喘臨床症狀及病理表現之間的關聯性。方法本研究包括兒童（1）氣喘或過敏性鼻炎，（2）異位性皮膚炎，但沒有氣喘或過敏性鼻炎，和（3）正常對照組。他們都接受血液採樣由西方點墨法或螢光激發細胞分類分析，來檢測單核細胞細胞中的β arrestin 2。氣喘嚴重程度、肺功能、嗜酸性白血球細胞計數、細胞激素、總免疫球蛋白E(IgE)及特異性IgE也被記錄。結果我們收集95台灣兒童進行評估，包括11名健康兒童，83例氣喘患者，只有1名兒童是異位性皮膚炎組。在西方點墨法這一組，在氣喘兒童β arrestin 2的平均值比的異位性皮膚炎組β arrestin 2高。在螢光激發細胞分類組，β arrestin 2量在兒童輕度持續性氣喘比輕度間歇性氣喘較高（p= 0.054）。β arrestin 2的值與總IgE的值有顯著的正相關（r= 0.254，p= 0.028）。結論我們的研究是第一次與人類的周邊血液單核球β arrestin 2濃度和氣喘孩童臨床表現之相關報告。總IgE的血清濃度可能可以預測β arrestin 2的表現。嗜酸性白血球細胞計數的量和β arrestin 2及總IgE血清濃度有交互作用。

關鍵字

氣喘；孩童；乙型制動素-2 ；總免疫球蛋白E ；西方點墨法；螢光激活細胞分選術

並列摘要

Introduction Asthma has been rapidly increasing in prevalence over decades in children as well as in adults. Beta-arrestins, originally discovered as molecules that bind to and desensitize the activated and phosphorylated form of the G protein-coupled beta2-adrenergic receptor (β2-AR), have recently emerged as multifunctional adaptor/scaffold proteins that dynamically assemble a wide range of multiprotein complexes. Furthermore, beta-arrestin 2 knockout animals had been found failure to develop the signs of allergic asthma (airway hyperreactivity). We conducted this study to survey the association between the levels of beta-arrestin 2 in peripheral blood mononuclear cells and clinopathological manifestations of asthma in Taiwanese children. Methods This study included children with (1) asthma or allergic rhinitis, (2) atopic dermatitis but without asthma or allergic rhinitis, and (3) normal control. They all received blood sampling for detecting β-arrestin 2 in PBMCs (peripheral blood mononuclear cells) by WB (Western blots) or FACS (Fluorescence Activated Cell Sorting). The asthma severity, eosinophil count, total IgE, specific IgE, cytokines, and lung function were also recorded. Results 95 Taiwan children are evaluated including 11 healthy children, 83 patients with asthma and only 1 child with atopic dermatitis. In the WB groups, the mean level of β-arrestin 2 in the asthmatic children was higher than the level of β-arrestin 2 in the only one child with atopic dermatitis. In our FACS results, the b-arrestin 2 amounts were higher in children with mild persistent asthma than mild intermittent asthma.(p=0.054) The expression level of β-arrestin 2 has a significantly positive correlation with total IgE (r=0.254, p=0.028). Conclusions Our study was the first report about that β-arrestin 2 may be involved in asthma by studying PBMCs in human. The serum levels of total IgE was a predictive factor of the expression of β-arrestin 2. The levels of eosinophil counts had interaction effect between the levels of b-arrestin 2 and total IgE.

並列關鍵字

Asthma ； Children ； Beta-arrestin 2 ； Total IgE ； WB(Western blots) ； FACS

參考文獻

Arroyave WD1, Rabito FA2, Carlson JC2.: The Relationship Between a Specific IgE Level and Asthma Outcomes: Results from the 2005-2006 National Health and Nutrition Examination Survey. J Allergy Clin Immunol Pract. 2013 Sep-Oct;1(5):501-508.

Azzi, M. et al. Beta-arrestin-mediated activation of MAPK by inverse agonists reveals distinct active conformations for G protein-coupled receptors. Proc. Natl Acad. Sci. USA 2003, 100: 11406–11411.

Bel EH: Clinical phenotypes of asthma. Curr Opin Pulm Med 2004, 10:44–50.

Bisset L.R. and Schmid–Grendelmeier P.: Chemokines and their receptors in the pathogenesis of allergic asthma: progress and perspective. Curr Opin Pulm Med 2004, 11:35–42.

Chialda L, Zhang M, Brune K, Pahl A. Inhibitors of mitogen-activated protein kinases differentially regulate co-stimulated T cell cytokine production and mouse airway eosinophilia. Respir Res 2005, 6: 36.

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台灣氣喘孩童血液中乙型制動素-2濃度高低與氣喘嚴重度及其臨床表徵之關聯性

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