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      小兒支氣管哮喘血T、B淋巴細(xì)胞異常表達(dá)的臨床意義

      2017-08-07 09:05:22王成林
      中國婦幼健康研究 2017年6期
      關(guān)鍵詞:外周血淋巴細(xì)胞支氣管

      文 勃,王成林,羅 麗,馮 楊

      (雅安市人民醫(yī)院,四川 雅安 625000)

      小兒支氣管哮喘血T、B淋巴細(xì)胞異常表達(dá)的臨床意義

      文 勃,王成林,羅 麗,馮 楊

      (雅安市人民醫(yī)院,四川 雅安 625000)

      目的 探討小兒支氣管哮喘血T、B淋巴細(xì)胞異常表達(dá)的臨床意義。方法 選擇2016年1至10月在雅安市人民醫(yī)院就診的哮喘患兒198例為研究對(duì)象(哮喘組),按照1:1配對(duì),隨機(jī)選取同期體檢兒童為對(duì)照組;在哮喘組患兒中急性發(fā)作期107例,緩解期91例,對(duì)照組198例。檢測哮喘急性發(fā)作、哮喘緩解和對(duì)照組兒童外周血的T淋巴細(xì)胞(CD3、CD3+CD4+、CD3+CD8+和CD4+/CD8+)、B淋巴細(xì)胞(CD19+CD23+),比較其相關(guān)指標(biāo)的差異。結(jié)果 哮喘組急性發(fā)作期患兒的CD3+CD4+、CD19+CD23+分別明顯高于哮喘緩解期(t值分別為2.479和2.341,均P<0.05)和對(duì)照組的患者(t值分別為2.421和2.524,均P<0.05);哮喘組急性發(fā)作期患兒的CD4+/CD8+明顯高于哮喘緩解期的患兒和對(duì)照組,經(jīng)比較均有顯著性差異(t值分別為2.516和2.325,均P<0.05)。結(jié)論 支氣管哮喘患兒外周血T、B淋巴細(xì)胞明顯異常高表達(dá),可作為支氣管哮喘輕重程度及治療效果的評(píng)價(jià)指標(biāo)。

      支氣管哮喘;B淋巴細(xì)胞;T淋巴細(xì)胞;兒童;治療效果

      支氣管哮喘(bronchial asthma,以下簡稱哮喘)是一種以慢性氣道炎癥和氣道高反應(yīng)性為特征的異質(zhì)性疾病,多于兒童期發(fā)病。雖然在西方發(fā)達(dá)國家哮喘的發(fā)病率趨于穩(wěn)定,但在發(fā)展中國家,其發(fā)病率呈逐年升高趨勢,成為嚴(yán)重影響兒童生長發(fā)育的慢性疾病之一,給患兒家庭及社會(huì)帶來了沉重的經(jīng)濟(jì)負(fù)擔(dān)。細(xì)胞免疫的主要執(zhí)行者為T淋巴細(xì)胞,體液免疫的主要執(zhí)行者為B淋巴細(xì)胞,淋巴細(xì)胞的失衡與小兒支氣管哮喘的發(fā)病密切相關(guān)[1-5]。T淋巴細(xì)胞和B淋巴細(xì)胞是否可作為小兒支氣管哮喘嚴(yán)重程度的評(píng)判標(biāo)準(zhǔn)及治療效果的隨訪指標(biāo)有待研究。本資料對(duì)198例哮喘患兒和按1:1配對(duì)同期體檢兒童的外周血T淋巴細(xì)胞(CD3、CD3+CD4+、CD3+CD8+和CD4+/CD8+)、B淋巴細(xì)胞(CD19+CD23+)進(jìn)行檢測分析,比較其相關(guān)指標(biāo)的差異,為探討外周血淋巴細(xì)胞相關(guān)指標(biāo)在小兒哮喘患兒中的臨床應(yīng)用價(jià)值提供理論依據(jù)。

      1對(duì)象與方法

      1.1研究對(duì)象

      收集2016年1至10月在雅安市人民醫(yī)院就診的哮喘患兒為研究對(duì)象(哮喘組),按照1:1配對(duì),隨機(jī)選取同期在本院體檢的兒童為對(duì)照組。將符合支氣管哮喘納入標(biāo)準(zhǔn)的患兒,根據(jù)有無臨床癥狀的急性發(fā)作分為急性發(fā)作期和緩解期。納入標(biāo)準(zhǔn):患兒年齡為1~14周歲,并符合兒童哮喘的臨床診斷標(biāo)準(zhǔn)[6];排除標(biāo)準(zhǔn):①年齡<1歲或者>14歲;②首次喘息發(fā)作;③近2周有糖皮質(zhì)激素或免疫調(diào)節(jié)劑的使用史;④合并有其他免疫性疾病、心肺腦基礎(chǔ)疾病等;⑤對(duì)照組兒童排除既往反復(fù)感染病史及喘息史,近2周有糖皮質(zhì)激素或免疫調(diào)節(jié)劑的使用史,存在特應(yīng)性體質(zhì)及過敏性疾病家族史,存在心肺腦基礎(chǔ)疾病和/或免疫疾病等基礎(chǔ)疾病。

      1.2標(biāo)本采集

      收集患兒的年齡、性別等基本信息,記錄淋巴細(xì)胞亞群主要參數(shù),包括T淋巴細(xì)胞(CD3、CD3+CD4+、CD3+CD8+和CD4+/CD8+)和B淋巴細(xì)胞(CD19+CD23+)及免疫球蛋白E(IgE)。采用MACSQuant八色流式細(xì)胞儀(德國)及貝克曼庫爾特Gallios流式細(xì)胞儀(美國)對(duì)標(biāo)本血進(jìn)行淋巴細(xì)胞亞群檢測。

      1.3統(tǒng)計(jì)學(xué)方法

      2結(jié)果

      2.1研究對(duì)象的一般資料

      本次共納入符合標(biāo)準(zhǔn)的研究對(duì)象396例。哮喘組198例,其中急性發(fā)作期患兒107例,占54.04%,哮喘緩解期患兒91例,占45.96%;對(duì)照組198例,見表1。

      2.2兩組T淋巴細(xì)胞亞群的檢測情況

      哮喘組急性發(fā)作期患兒的CD3+CD4+和CD4+/CD8+均明顯高于哮喘組緩解期患兒和對(duì)照組兒童,經(jīng)比較有顯著性差異(均P<0.05);哮喘組緩解期患兒的CD3+CD4+和CD4+/CD8+均高于對(duì)照組兒童,經(jīng)比較有顯著性差異(均P<0.05),見表2。

      組別總例數(shù)(n)性別人數(shù)平均年齡(歲)哮喘組198 急性發(fā)作期107男65(60.75)7.52±2.95女42(39.25)7.41±2.97 緩解期91男50(54.95)7.49±3.01女41(45.05)7.51±3.02對(duì)照組198男102(51.52)7.53±2.96女96(48.48)7.51±2.97

      組別CD3+CD3+CD4+CD3+CD8+CD4+/CD8+哮喘組 急性發(fā)作期63.72±4.1837.82±1.9823.98±2.091.57±0.09 緩解期62.97±3.7930.19±1.8724.12±1.991.25±0.08對(duì)照組62.01±3.8227.68±1.7923.82±2.111.16±0.04t11.3472.4791.4272.516P1>0.05<0.05>0.05<0.05t21.4162.4211.3762.325P2>0.05<0.05>0.05<0.05t31.3972.4711.5382.419P3>0.05<0.05>0.05<0.05

      注:t1和P1為哮喘組急性發(fā)作期與緩解期之間的比較;t2和P2為哮喘組急性發(fā)作期與對(duì)照組之間的比較;t3和P3為哮喘組緩解期與對(duì)照組之間的比較。

      2.3兩組B淋巴細(xì)胞和IgE的檢測情況

      哮喘組急性發(fā)作期患兒的CD19+CD23+明顯高于哮喘組緩解期患兒和對(duì)照組兒童,經(jīng)比較均有顯著性差異(均P<0.05);哮喘組急性發(fā)作期患兒IgE明顯高于哮喘組緩解期患兒和對(duì)照組兒童,經(jīng)比較均有顯著性差異(均P<0.05),見表3。

      組別CD19+CD23+IgE(mIU/mL)哮喘組 急性發(fā)作期25.82±5.86256.79±79.82 緩解期13.78±2.99178.42±81.54對(duì)照組4.18±2.0965.41±21.32t12.3412.421P1<0.05<0.05t22.5242.379P2<0.05<0.05t32.3372.282P3<0.05<0.05

      注:t1和P1為哮喘組急性發(fā)作期與緩解期之間的比較;t2和P2為哮喘組急性發(fā)作期與對(duì)照組之間的比較;t3和P3為哮喘組緩解期與對(duì)照組之間的比較。

      3討論

      支氣管哮喘被認(rèn)為是遺傳、環(huán)境、免疫病理機(jī)制共同參與的多基因遺傳性疾病。支氣管哮喘的具體發(fā)病機(jī)制尚未明確,但免疫機(jī)制在哮喘發(fā)生發(fā)展中的作用成為近年來的研究熱點(diǎn),以期為哮喘的診斷、治療、控制提供新的方向。有研究顯示體內(nèi)細(xì)胞免疫失衡與哮喘發(fā)生、發(fā)展存在密切關(guān)系[7-11]。

      3.1血清T淋巴細(xì)胞異常表達(dá)在小兒支氣管哮喘中的臨床意義

      作為細(xì)胞免疫的主要功能執(zhí)行者,T淋巴細(xì)胞受不同協(xié)同刺激信號(hào)影響,其中CD4/CD8比值平衡是維持機(jī)體免疫平衡的關(guān)鍵環(huán)節(jié),機(jī)體在受到變應(yīng)原刺激后,外周T細(xì)胞亞群含量會(huì)出現(xiàn)異常變化,速發(fā)性哮喘多見CD8+細(xì)胞水平下降,遲發(fā)性哮喘多見CD4+細(xì)胞水平增多[12-13]。本研究結(jié)果顯示,哮喘組急性發(fā)作期患兒的CD3+CD4+和CD4+/CD8+均分別明顯高于哮喘組緩解期患兒和對(duì)照組兒童(均P<0.05),說明患兒血清T淋巴細(xì)胞水平與患者疾病狀態(tài)密切相關(guān),可作為支氣管哮喘輕重程度及治療效果的評(píng)價(jià)指標(biāo)。

      3.2外周血B淋巴細(xì)胞異常表達(dá)在小兒支氣管哮喘中的臨床意義

      體液免疫的主要執(zhí)行者為B淋巴細(xì)胞。CD19和CD23分別是B淋巴細(xì)胞膜上的特征標(biāo)志及IgE的低親和力受體,其中CD23可介導(dǎo)細(xì)胞間的粘附,促進(jìn)嗜堿性粒細(xì)胞釋放組胺,調(diào)節(jié)IgE的合成和分泌,觸發(fā)IgE介導(dǎo)炎癥遞質(zhì)的釋放和Ⅰ型變態(tài)反應(yīng)的產(chǎn)生[14-16]。本研究中哮喘組急性發(fā)作期患兒的CD19+CD23+和IgE均明顯高于哮喘組緩解期患兒和對(duì)照組兒童(均P<0.05),說明患兒血清B淋巴細(xì)胞水平及與IgE水平患者疾病狀態(tài)密切相關(guān),可作為支氣管哮喘輕重程度及治療效果的評(píng)價(jià)指標(biāo)。

      總之,支氣管哮喘患兒外周血T、B淋巴細(xì)胞明顯異常高表達(dá),可作為支氣管哮喘病情程度及治療效果的評(píng)價(jià)指標(biāo)。本研究的不足為樣本量較小,更重要的結(jié)果還有待多中心、大樣本的研究證實(shí)。

      [1]Ishimori A, Harada N, Chiba A,etal.Circulating activated innate lymphoid cells and mucosal-associated invariant T cells are associated with airflow limitation in patients with asthma[J].Allergol Int,2017,66(2):302-309.

      [2]Chu M, Chu I M, Yung E C,etal.Aberrant expression of novel cytokine IL-38 and regulatory T lymphocytes in childhood asthma[J].Molecules,2016,21(7):E933.

      [3]Amin K.The role of the T lymphocytes and remodeling in asthma[J].Inflammation,2016,39(4):1475-1482.

      [4]Raemdonck K, Baker K, Dale N,etal.CD4+ and CD8+ T cells play a central role in a HDM driven model of allergic asthma[J].Respir Res,2016,17:45.

      [5]Zuska-Prot M, Ziókowski H, Jaroszewski J J,etal.Distribution of CD4+CD8+ double positive T cells in a mouse model of allergic asthma[J].Pol J Vet Sci,2016,19(1):217-219.

      [6]中華醫(yī)學(xué)會(huì)呼吸病學(xué)分會(huì)哮喘學(xué)組.支氣管哮喘防治指南(2016年版)[J].中華結(jié)核和呼吸雜志,2016,39(9):675-697.

      [7]Ling M F, Luster A D.Allergen-specific CD4(+) T cells in human asthma[J].Ann Am Thorac Soc,2016,Suppl 1:S25-S30.

      [8]Troy N M, Hollams E M, Holt P G,etal.Differential gene network analysis for the identification of asthma-associated therapeutic targets in allergen-specific T-helper memory responses[J].BMC Med Genomics,2016,9:9.

      [9]Yang S H, Yu C L, Yang Y H,etal.The immune-modulatory effects of a mixed herbal formula on dendritic cells and CD4+ T lymphocytes in the treatment of dust mite allergy asthma and perennial allergic rhinitis[J].J Asthma,2016,53(4):446-451.

      [10]Schedel M, Jia Y, Michel S,etal. 1,25D3 prevents CD8(+)Tc2 skewing and asthma development through VDR binding changes to the Cyp11a1 promoter[J].Nat Commun,2016,7:10213.

      [11]Wang W, Li P, Yang J.Decreased circulating interleukin-35 levels are related to interleukin-4-producing CD8+ T cells in patients with allergic asthma[J].Iran J Allergy Asthma Immunol,2015,14(4):379-385.

      [12]Li X M, Peng J, Gu W,etal.TCDD-iInduced activation of Aryl hdrocarbon receptor inhibits Th17 polarization and regulates non-eosinophilic airway inflammation in asthma[J].PLoS One,2016,11(3):e0150551.

      [13]Tao B, Ruan G, Wang D,etal.Imbalance of peripheral Th17 and regulatory T cells in children with allergic rhinitis and bronchial asthma[J].Iran J Allergy Asthma Immunol,2015,14(3):273-279.

      [14]Haenen S, Vanoirbeek J A, De Vooght V,etal.Proteomic alterations in B lymphocytes of sensitized mice in a model of chemical-induced asthma[J].PLoS One,2015,10(9):e0138791.

      [15]Kamekura R, Shigehara K, Miyajima S,etal.Alteration of circulating type 2 follicular helper T cells and regulatory B cells underlies the comorbid association of allergic rhinitis with bronchial asthma[J].Clin Immunol,2015,158(2):204-211.

      [16]Hong G U, Lim J Y, Kim N G,etal.IgE and IgA produced by OX40-OX40L or CD40-CD40L interaction in B cells-mast cells re-activate FcεRI or FcαRI on mast cells in mouse allergic asthma[J].Eur J Pharmacol,2015,754:199-210.

      [專業(yè)責(zé)任編輯:侯 偉]

      Clinical significance of abnormal expressions of T and B lymphocytes in children with bronchial asthma

      WEN Bo, WANG Cheng-lin, LUO Li, FENG Yang

      (Ya’an People’s Hospital, Sichuan Ya’an 625000, China)

      Objective To investigate the clinical significance of abnormal expressions of T and B lymphocytes in children with bronchial asthma. Methods Altogether 198 children with bronchial asthma treated in Ya’an People’s Hospital from January to October in 2016 were selected as study objects (asthma group), and healthy children receiving physical examination at the same time were randomly selected as control group according to 1:1 matching. In asthma group there were 107 cases in acute stage and 91 cases in remission stage, and 198 children were in the control group. T lymphocyte (CD3, CD3+CD4+, CD3+CD8+ and CD4+/CD8+) and B lymphocyte (CD19+CD23+) in peripheral blood of children in acute stage and in remission stage and of children in the control group were tested, and relative indexes were compared. Results Levels of CD3+CD4+ and CD19+CD23+ of cases in acute stage were significantly higher than those in remission stage (tvalue was 2.479 and 2.341, respectively, bothP<0.05) and those in the control group (tvalue was 2.421 and 2.524, respectively, bothP<0.05). Level of CD4+/CD8+ of cases in acute stage was significantly higher than that of cases in remission stage and in the control group, and the differences had statistic significance (tvalue was 2.516 and 2.325, respectively, bothP<0.05). Conclusion Expressions of T and B lymphocytes in peripheral blood of children with bronchial asthma are obviously high-expressed, which can be used as an index to evaluate the severity and therapeutic effect of bronchial asthma.

      bronchial asthma; B lymphocytes; T lymphocytes; children; therapeutic effect

      2016-11-08

      文 勃(1980-),男,主治醫(yī)師,主要從事兒科臨床工作。

      王成林,主任醫(yī)師。

      10.3969/j.issn.1673-5293.2017.06.014

      R562.2

      A

      1673-5293(2017)06-0659-03

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