IgE和非IgE介导的儿童变态反应的免疫表型
中文摘要
背景：IgE介导和非IgE介导儿童变态反应在临床治疗方面没有区别，但治疗并不完全有效。
目的：研究试图明确在IgE介导和非IgE介导的变态反应中是否存在新的免疫表型，儿童时期的变态反应的免疫机制并不十分清楚，往往是通过研究Th1/Th2
细胞典型的炎症细胞因子来解释的，最初研究目的是通过测定血清IL-17的水平来判断在非IgE介导的变态反应中Th17细胞的新的免疫表型。
方法：从门诊或住院病人中收集既往或目前有变态反应疾病史的患儿，取静脉血2ml，离心后取血清冷冻保存，采用酶联免疫吸附法（ELISA）检测其过敏原特异性IgE抗体及血清总IgE的水平，并测定血清中炎症细胞因子IL-17、IFN-γ、IL-5、IL-9和IL-13的水平，根据患儿就诊时有无合并感染情况的不同，将这37份标本分为变态反应组（A）、感染组（B）、变态反应合并感染组（C）和其他（D）共四组，统计采用SPSS17.0软件分析数据，P<0.05，表示有统计学意义。结果：（1）在37份患儿血清标本中A组13例，B组7例，C组14例，D组3例。（2）在A、B、C三组中IgE升高的共有29例(占总病例数的78.38%)，其中A组有10例（76.92%），B组有7例（100%），C组有12例（85.71%）。（3）在A、B
、C三组中EOS增高者有13例(占总病例数的38.2%)，A组5例（38.5%），B组3例（42.9%），C组5例（35.7%）。（4）在A、B、C三组中IgE升高同时伴有EOS数量升高的有12例，占总病例数的35.3%。（5）将A 组分为IgE阳性组和IgE阴性组，细胞因子IL-17在这两组间均无显著性差异（P=0.828，95%CI为-0.84，1.03）。（6）在A、B、C三组间IFN-γ、IL-13、IL-17、IL-5和IL-9细胞因子水平也均无显著性差异（P值和95%CI分别为0.495，[3.93，9.00]；0.244，[10.32,16.58]；0.407，[0.95,1.33]；0.62，[1.96,3.08]；0.345，[2.03,3.12]），P值均>0.05。（7）一例JIA个案的血清中IL-13水平正常，IFN-γ、IL-17、IL-5、IL-9水平明显升高。
结论：变态反应患儿容易合并感染，伴随感染是患儿就诊的主要原因。在本研究
1
收集的病例中，总IgE增高较多见，在变态反应的临床诊断中，总IgE水平或EOS增高并无相关性，IgE与EOS同时增高与变态反应的临床诊断相关性较低。IL-17在非IgE与IgE介导的变态反应中的水平无显著差异，表明在这两种变态反应免疫表型中Th17细胞的参与程度较低，理论上皮质类固醇治疗对多数变态反应仍应有效。血清炎症细胞因子对变态反应、感染和变态反应合并感染等病情并无显著免疫表型的鉴别作用。一例JIA除Th2细胞炎症因子表达强烈，IL-9表达也显著增高。Th9细胞（滤泡性辅助性T细胞）及其所分泌的IL-9炎症因子在JIA的发病机制中的作用有待探讨和进一步证实。
[关键词]非IgE介导；变态反应；Th17细胞；细胞因子；免疫表型
Identification of immune phenotypes for IgE mediated and non-IgE
mediated allergic in childhood
Abstract
Background:Childhood allergy is classified into IgE mediated allergy and non-IgE mediated allergy,yet both are treated identically,with only partial success. Objective:We sought to identify novel immune phenotypes for childhood IgE mediated and non-IgE mediated allergy.The immune mechanisms that underlie allergy remain ill-defined and controversial in childhood,in part becau studies in humans typically focus on analysis of a limited number of prototypical Th1/Th2 cytokines.Our primary focus is identification of novel indicators of Th17 dysregulation.
Method:The study includes37individuals(patients with allergy[groupA],patients with infection[group B],allergy accompany with infection[groupC],and others dia[groupD]).In rum both quantitative and functional analysis of cytokines expression(IFN-gamma,IL-13,IL-17,IL-5,IL-9)were performed.Total IgE and specific IgE antibody of inspiratory or ingested assd by using half quant
itative ELISA.Linear discriminant analysis was applied to discriminate between phenotypes.U sing SPSS17.0software,d ata are prented as the mean±standard error of themean(SEM)and performed with one-way analysis ofvariance(ANOVA) followed by Tukey’s multiple comparisontest to compare the mean levels of cytokine expression.All p-values less than0.05were considered statistically significant. Results:(1)In the37rum samples13cas were included in group A and group B had7cas,group C had14cas,group D had3cas.(2)In A,B,C three groups elevated IgE were29cas,including10cas of group A,group B had7cas,there were12cas of group C.(3)A,B,C three groups EOS levels ri were13cas, accounting for38.2%,group A had five cas,accounting for38.5%,in group B had3 cas,accounting for about42.9%,group C had five cas,accounting for35.7%.(4)
IgE incread in A,B,C three groups accompanied with EOS incread the number were12cas,accounting for35.3%.(5)According to with or without infection the group A was divided into elevated IgE group and IgE not high group the two groups, IL-17and IFN-γ,IL-5,IL-9,IL-13expression levels in the two groups were no significant difference(P>0.05).(6)IFN-γ,IL-13,IL-17,IL-5and IL-9expression levels showed no significant difference in A,B and C groups(p value and95%CI, IFN-γ,p=0.495，95%CI[3.93，9.00]；IL-13,p=0.244，95%CI[10.32,16.58]；IL-17, p=0.407，95%CI
[0.95,1.33]；IL-5,p=0.62，95%CI[1.96,3.08]；IL-9,p=0.345，95%CI[2.03,3.12]respectively).The A,B and C groups patients were immunologically no better discriminated by means of cytokines and IgE analysis with linear discriminant analysis.(7)One JIA cas of rum IL-13expression were normal,IFN-γ,IL-17,IL-5,IL-9expression levels were significantly incread. Conclusions:In summary,the majority of persons with allergy had an uncomplicated cour;however,infection dia,including virus infection and bacterial infection, occurred in allergy patients who prented with comorbities.The immune phenotypes should be expresd complex.Tho IgE or EOS incread in the clinical diagnosis of allergy has little significance,IgE and EOS at the same time incread in clinical diagnosis of allergic reactions also is not specific.No significant difference of IL-17in IgE mediated and non-IgE mediated allergic ,the participation of Th17cells is lower in the two allergic reactions,the effectiveness of corticosteroids therapy for the most allergy is good.JIA expression of proinflammatory cytokines except Th2cells strongly,Th9cells(follicular helper T cells)and creted IL-9may be in the pathogenesis of JIA has also played an important role.Identification of the unique cytokines did not provides a profound basis for future strategies for individualized prediction of allergy development,dia cour,and prevention. [Key words]:non-IgE mediated,allergy,Th17cells,cytokine,immune phenotype
IgE和非IgE介导的儿童变态反应的免疫表型Identification of immune phenotypes for IgE mediated and non-IgE
mediated allergic in childhood
前言
变态反应性疾病是一种十分复杂的免疫学疾病，随着社会工业化程度的不断提高以及对感染性疾病的不断控制，近20年来，呈逐年增加的趋势，目前已成为全球性健康问题。支气管哮喘、过敏性鼻炎、过敏性皮肤病等是临床上最常见的变态反应性疾病。变态反应性疾病在儿童的发病率高达40％[1]。变态反应是由异常的免疫机制介导的特异性的变应原反应，而由异常的免疫机制介导的变态反应可分为两类，一类是由IgE介导的I型变态反应，通常可以累及呼吸道、消化道、皮肤等多种器官、组织，多于接触变应原后几分钟内出现临床症状；另一类是由非IgE介导的变态反应，多于接触变应原几小时或数天后出现症状，其发病涉及了多种免疫学机制，包括免疫复合物、IgG及细胞毒细胞介导的变态反应等。
Thl和Th2细胞的免疫功能失衡被认为是经典的“卫生假说”的基础。该假说认为机体Th1细胞功能发育障碍是由于目前的生活环境相对较为干净，暴露于感染性致病原机率减少，以及大量使用抗生素等所导致的，从而降低了机体免疫功能，使机体容易发生过敏反应，而导致哮喘的发病[2]。目前越来越多的
研究发现支气管哮喘的发病机制远较Thl/Th2细胞失衡学说复杂的多。即由IgE介导的变态反应的发病机制，也不能仅用“卫生假说”来解释，尤其是非IgE介导的变态反应，其发病机制的研究文献目前较少。但是有研究发现，在支气管哮喘病人诱导的痰液中除嗜酸性粒细胞外，其他的炎症细胞，包括中性粒细胞、肥大细胞、T淋巴细胞的比例明显增加，其中中性粒细胞的数量最多，在一些重症持续性哮喘患者气道内的炎性细胞及介质并不是以嗜酸性粒细胞为主[3]，也不是以IgE为主，而是属于其他炎性细胞导致的哮喘。近期的研究发现，Thl7细胞及其分泌的主要效应细胞因子IL-17在过敏性哮喘、变应性鼻炎、特应性皮炎等变态反应性疾病的炎症反应中发挥了重要作用。Th17细胞是存在于机体内的一种不同于Th1和Th2细胞的T细胞亚群，它是由初始的CD4+T细胞分化而来，Th17细胞
