江伯倫Chiang, Bor-Luen臺灣大學:臨床醫學研究所林聖傑Lin, Sheng-ChiehSheng-ChiehLin2010-05-102018-07-062010-05-102018-07-062009U0001-0908200916580400http://ntur.lib.ntu.edu.tw//handle/246246/181670異位性皮膚炎是一種過敏性之濕疹，小朋友在其臨床表徵上包括了極端之搔癢感，分布之區域常在臉部、四肢伸側之皮膚上，這些小朋友在長大之後，也發現皮膚會有慢性發炎和反覆發作之情況。異位性皮膚炎在臨床上常常可以發現免疫球蛋白E(Ig E)和嗜酸性白血球的增加。最近有醫學研究指出異位性皮膚炎和氣喘、過敏性鼻炎一樣與第二型輔助T細胞(Th2 cell)有關。第二型輔助T細胞在過敏體質的小朋友會分泌較多的介白質4 (IL-4)和介白質5 (IL-5)。當介白質4 和介白質4接受器反應時，會使得 Janus Kinases 磷酸化，使的signal transducers and activators of transcription 6 (STAT6)形成雙合體進入細胞核與特定之基因反應，接著免疫球蛋白class switch 產生免疫球蛋白E。介白質4和介白質5已發現與異位性皮膚炎有關，然而陸續有些其他新的介白質也被發現與過敏有相關。最進研究發現介白質21 (IL-21)為新的細胞激素，其為介白質2家族的其中一種，其主要是由活化的CD4+ T 淋巴球細胞所分泌。少部分是由第十七型輔助T細胞(Th17 cell)細胞所分泌的。在動物實驗模式上，介白質21似乎會藉由不同的作用機制降低免疫球蛋白E的製造。而到目前為止，並沒有臨床的資料明確的指出在小朋友中，異位性皮膚炎和介白質21的相關性。在這個研究中，我們採取實驗組與對照組的研究方法。利用SCORAD量表，評估異位性皮膚炎之臨床嚴重度。藉著uni-CAP system，測量血漿中總免疫球蛋白E及特異性過敏原的免疫球蛋白E的濃度。將PBMC在RPMI中予以做細胞培養。同時使用both anti-CD3 and anti-CD28 (2μg/ml) Ab 或 PHA (2μg/ml) 或PWM (4 μg/ml)予以刺激。並利用酵素免疫分析法(ELISA) 之實驗方法，量測介白質21、介白質4、介白質5、干擾素-γ、介白質17的細胞激素濃度。總共收案75 個小朋友(男性37位，女性38位)。血漿中總免疫球蛋白E 在實驗組和對照組中測得為 365.4 +/- 51.81 IU/ml 和36.68+/- 6.845 IU/ml (P<0.0001) 。測量介白質21之濃度，發現實驗組較對照組有較低的介白質21。同時，利用迴歸分析，發現介白質21與介白質4並無相關性，介白質21與介白質5並無相關性，介白質21與介白質17並無相關性。而介白質21與干擾素-γ似乎有正相關性(r2=0.402,P<0.05) 。除此之外，異位性皮膚炎皮膚嚴重程度輕度的較皮膚嚴重程度重度的在血中有顯著較高濃度的介白質21。因此我們認為介白質21對於異位性皮膚炎是一個重要的細胞激素，並且有其重要的角色。Atopic dermatitis is one form of eczema that is characterized by typical distribution, extreme pruritus, and chronically relapsing course. Recent studies have demonstrated that atopic dermatitis, like asthma and allergic rhinitis, is associated with the local infiltration of T helper type 2 (Th2) cells that secrete interleukin (IL)-4, IL-5, and IL-13. In atopic dermatitis, increased total serum IgE levels are common characteristics. Molecular events in immunoglobulin E (IgE) isotype switching require IL-4 or IL-13 stimulation interaction with their receptors that lead to the phophorylation (by Janus Kinases) and transduction of signal transducers and activators of transcription 6 (STAT6) into the nucleus, inducing target genes and the production of IgE. IL-4 and IL-5 was already confirmed association with atopic dermatitis. Recent studies revealed IL-21 is a new member of IL-2 family cytokine. IL-21 is mainly expressed by activated CD4+ T lymphocytes. Th17 cells produced few number of IL-21. In animal study, IL-21 had its ability to down-regulate IgE production and had negatively regulation in IgE isotype switching by several mechanisms. Until now, there was no clinical data show the relationship between IL-21 and atopic dermatitis. By the method of case and control study, we checked serum total IgE, specific IgE. We also evaluate the effects and relationship between IL-21, IL-4, IL-5, IFN-γ and IL-17 in atopic dermatitis of children. SCORAD index were used primarily in clinical severity. Total serum IgE and allergen specific-IgE was checked by uni-CAP system. Cell culture with PBMC was stimulated with both anti-CD3 and anti-CD28 Ab (2μg/ml) or PHA (2μg/ml) or PWM (4 μg/ml). The cytokine level of IL-21, IL-4, IL-5, IFN-γand IL-17 were checked by ELISA method. A total number of 75 children were enrolled (male 37, female 38). Serum total IgE in the case group and control group were measured as 365.4 +/-51.81 IU/ml and 36.68+/- 6.845 IU/ml (P<0.0001). IL-21 levels in children with atopic dermatitis were lower than healthy control children. By using logistic regression analysis, it was found that there was no correlation between IL-21 and IL-4, IL-21 and IL-5, IL-21 and IL-17. There was significant correlation between IL-21 and IFN-γ (r2=0.402, P<0.05). Besides, severe atopic dermatitis was significantly higher concentrations of IL-21 than mild atopic dermatitis (P <0.05). We found that IL-21 was an important cytokine and play an important role in atopic dermatitis.口試委員會審書1謝2錄3文摘要4-5文摘要6-7一章 緒論8一節 研究背景9-11二節 研究的假說與目的.12-13二章 研究方法14一節 病人收集15二節 材料使用16三節 實驗方法17-18四節 統計分析19五節 實驗流程20三章 結果21一節 族群分析22二節 總免疫球蛋白E與過敏原特異性免疫球蛋白E抗體之分析23三節 細胞激素的分析24-28四節 細胞激素之間的相關連性29五節 臨床表徵不同嚴重性與介白質21濃度之差異性30四章 討論31-35五章 展望36-37考文獻38-41錄42-78application/pdf407695 bytesapplication/pdfen-US介白質21異位性皮膚炎免疫球蛋白E過敏Interleukin-21atopic dermatitisIgE isotype switchallergyhttp://ntur.lib.ntu.edu.tw/bitstream/246246/181670/1/ntu-98-P96421018-1.pdf