探討T細胞上表現之唾液酸化醣基與孩童氣喘內表現型的相關

Abstract

背景：氣喘是一種常見的孩童慢性發炎疾病。在氣喘的致病機轉中，輔助型T細胞和調節型T細胞對氣喘內表現型的產生扮演非常關鍵的角色。在其他過敏性疾病中發現，輔助型記憶T細胞上表現之sialyl Lewis x (CD15s) 與sialyl 6-sulfo Lewis x (G152) 醣基與疾病的嚴重程度具有相關性。這些唾液酸化醣基與氣喘內表現型的相關性仍不清楚，需要做更進一步的檢驗。 方法：收案對象為2015及2016間至台大兒童醫院與一間診所就診之6至15歲孩童，包含31位氣喘患者與19位健康個案。我們使用流式細胞儀檢測輔助型記憶T細胞上帶有唾液酸化醣基的百分比與氣喘嚴重程度、血液中嗜酸性球、血液中免疫球蛋白E等氣喘內表現型指標的相關性。 結果：氣喘患者之CD15s與G152醣基的表現量和健康個案相比有顯著的上升。T細胞中具有高度抑制功能之CD15s+調節型T細胞族群則被發現在中度至重度氣喘患者的組別有顯著的下降。血液中嗜酸性球與血液中免疫球蛋白E兩個氣喘惡化指標分別與G152和G159醣基有相關。 結論：CD15s與G152醣基與孩童氣喘當下的狀態有關。氣喘患者其中樞輔助型記憶T細胞上表現較多的G152醣基或表現較少G159醣基可能會有較高氣喘惡化的風險。

Background: Asthma is a common chronic inflammatory disease in children. Helper T (Th) cells and regulatory T cells (Tregs) play important role of the pathogenesis of asthma and lead to various endophenotypes. The expression level of functional adhesion molecules, sialyl Lewis x (CD15s) and sialyl 6-sulfo Lewis x (G152) glycan, on memory Th cells are associated with the severity of allergic diseases. The association between the expression level of sialyl glycans and asthma endophenotypes remain unclear and needs further investigation. Methods: Thirty-one asthma patients and nineteen healthy controls aged 6 to 15 were recruited from NTUCH and a clinic in 2015 and 2016. The percentage of glycan-expressing cells among memory Th cells was detected by flow cytometry. The association between the expression of sialyl glycan and several asthma endophenotypes, such as severity, blood eosinophils and serum total IgE level, was investigated. Results: CD15s and G152 glycans on memory Th cells are upregulated in asthma patients compared with healthy controls. The population of suppressive CD15s+ Tregs among CD4+ T cells was significantly lower in the moderate to severe group of asthma. Blood eosinophils and serum total IgE and, as two indicators of the exacerbation of asthma were associated with G152 glycan and G159 glycan respectively. Conclusions:CD15s and G152 glycans were associated with the current status of childhood asthma. Patients expressing the higher level of G152 glycan and less G159 glycan on central helper memory T cells would have higher risk on exacerbation.