本文選題：CD19+CD24highCD38high + CD19+CD24highCD27+　； 參考：《蘇州大學(xué)》2015年博士論文

【摘要】：一、人CD19+CD24highCD38high及CD19+CD24highCD27+調(diào)節(jié)性B細(xì)胞特性的研究目的:探討人外周血CD19+CD24highCD38high及CD19+CD24highCD27+調(diào)節(jié)性B細(xì)胞的特性。方法:流式細(xì)胞儀檢測(cè)健康志愿者外周血單個(gè)核細(xì)胞中CD19CD24CD38及CD19+CD24highCD27+調(diào)節(jié)性B細(xì)胞(regulatory B cell,Breg)的比例及其凋亡、增殖、B細(xì)胞活化因子受體(B-cell activating factor receptor,BAFF-R)、跨膜蛋白活化因子鈣離子信號(hào)調(diào)節(jié)親環(huán)素配體(transmembrane activator calcium modulatorand cyclophilin ligand interactor,TACI)、B細(xì)胞成熟抗原(B cell maturation Ag,BCMA)、結(jié)合的B細(xì)胞活化因子(B-cell activating factor belonging to the TNF family,BAFF)及一種增殖誘導(dǎo)配體(a proliferation-inducing ligand,APRIL)水平、T細(xì)胞免疫球蛋白黏蛋白結(jié)構(gòu)域相關(guān)分子-3(T cell Ig domain and mucin domain 3,Tim-3)表達(dá)、CD20表達(dá)、CD80表達(dá)及CD86表達(dá)。分別經(jīng)CD40L及Cp G ODN2006刺激后檢測(cè)CD19+CD24highCD38high、CD19+CD24highCD27+Breg細(xì)胞分泌的IL-10、TGF-β水平。將CD19+CD24highCD38high與CD19+CD24highCD27+Breg細(xì)胞、CD19+CD24highCD38high與非Breg、CD19+CD24highCD27+與非Breg之間進(jìn)行上述指標(biāo)的比較。結(jié)果:在正常人外周血單個(gè)核細(xì)胞中CD19+CD24highCD38high Breg比例為5.88%3.18%,CD19+CD24highCD27+Breg的比例為14.10%±9.47%,CD19+CD24highCD27Breg的比例高于CD19+CD24highCD38high Breg(P=0.000)。CD19+CD24highCD38high Bre與CD19+CD24highCD27+Breg相比凋亡水平無(wú)差異(28.87%±14.82%vs.28.84%18.33%,P=0.994),CD19+CD24highCD38high Breg與非CD19+CD24highCD38high細(xì)胞相凋亡水平亦無(wú)差異(28.87%±14.82%vs.23.86%±11.17%,P=0.994),而CD19+CD24highCD27+Breg凋亡水平高于非CD19+CD24highCD27+細(xì)胞(28.84%±18.33%vs.14.93%±7.83%,P=0.002)。CD19+CD24highCD38high Breg與CD19+CD24highCD27+Breg相比增殖水平差異無(wú)統(tǒng)計(jì)學(xué)意義(21.46%±11.88%vs.17.28%±13.18%,P=0.442),CD19+CD24highCD38high Breg增殖水平高于非CD19+CD24highCD38high細(xì)胞(21.46%±11.88%vs.6.22%±10.07%,P=0.009),CD19+CD24highCD27+Breg增殖水平與非CD19+CD24highCD27+細(xì)胞相比差異無(wú)統(tǒng)計(jì)學(xué)意義(17.28%±13.18%vs.12.96%±11.93%,P=0.570)。CD19+CD24highCD38high Breg細(xì)胞與CD19+CD24highCD27+Breg細(xì)胞均表達(dá)BAFF-R、TACI、BCMA,并且兩群細(xì)胞間BAFF-R、TACI、BCMA的表達(dá)差異無(wú)統(tǒng)計(jì)學(xué)意義(BAFF-R:97.17%±6.17%vs.96.46%±8.64%,P=0.743;TACI:65.84%±28.60%vs.71.43%±36.51%,P=0.558;BCMA:91.15%±9.62%vs.90.28%±13.61%,P=0.799)。CD19+CD24highCD38high Breg細(xì)胞BAFF-R、TACI的表達(dá)高于非CD19+CD24highCD38high細(xì)胞(97.17%±6.17%vs.89.56%±7.43%、65.84%±28.60%vs.39.07%±23.92%,P=0.000、0.002),而BCMA的表達(dá)(94.13%±3.15%)無(wú)差異(P=0.495)。CD19+CD24highCD27+Breg細(xì)胞BAFF-R、TACI、BCMA的表達(dá)與非CD19+CD24highCD27+細(xì)胞(98.71%±1.10%、56.14%±28.75%、94.50%±4.08%)相比差異均無(wú)統(tǒng)計(jì)學(xué)意義(P=0.142,0.130,0.481)。CD19+CD24highCD38high Breg細(xì)胞與CD19+CD24highCD27+Breg細(xì)胞結(jié)合BAFF、APRIL的水平差異均無(wú)統(tǒng)計(jì)學(xué)意義(55.24%±17.46%vs.54.42%±20.36%,P=0.882;61.95%±31.66%vs.63.97%±35.07%,P=0.835)。CD19+CD24highCD38high Breg細(xì)胞結(jié)合BAFF的水平與非CD19+CD24highCD38high細(xì)胞相比差異無(wú)統(tǒng)計(jì)學(xué)意義(55.24%±17.46%vs.58.95%±12.59%,P=0.424),而結(jié)合APRIL的水平高于非CD19+CD24highCD38high細(xì)胞(55.24%±17.46%vs.35.29%±22.08%,P=0.002)。CD19+CD24highCD27+Breg細(xì)胞與非CD19+CD24highCD27+細(xì)胞相比結(jié)合BAFF、APRIL的水平(59.05%±15.89%,57.76%±33.04%)差異均無(wú)統(tǒng)計(jì)學(xué)意義(P=0.404,0.546)。CD19+CD24highCD38high Breg細(xì)胞Tim-3表達(dá)水平高于CD19+CD24highCD27+Breg(14.27%±6.97%vs.6.91%±5.88%,P=0.014),CD19+CD24highCD38high Breg細(xì)胞Tim-3表達(dá)水平高于非CD19+CD24highCD38high細(xì)胞(14.27%±6.97%vs.1.44%±1.71%,P=0.000),CD19+CD24highCD27+Breg細(xì)胞Tim-3表達(dá)水平高于非CD19+CD24highCD27+細(xì)胞(6.91%±5.88%vs.1.99%±2.01%,P=0.002)。CD19+CD24highCD38high Breg與CD19+CD24highCD27+Breg相比CD20表達(dá)水平差異無(wú)統(tǒng)計(jì)學(xué)意義(96.89%±7.90%vs.97.12%±5.44%,P=0.912),CD19+CD24highCD38high Breg細(xì)胞CD20表達(dá)水平高于非CD19+CD24highCD38high細(xì)胞(88.67%±9.22%,P=0.004),CD19+CD24highCD27+Breg細(xì)胞CD20表達(dá)水平與非CD19+CD24highCD27+細(xì)胞(96.76%±3.38%)相比差異無(wú)統(tǒng)計(jì)學(xué)意義(P=0.798)。經(jīng)CD40L刺激后分泌IL-10、TGF-β的CD19+CD24highCD38high Breg細(xì)胞比例(7.81%±2.67%,7.05%±2.66%)與CD19+CD24highCD27+Breg(7.17%±2.47%,8.14%±2.44%)相比差異均無(wú)統(tǒng)計(jì)學(xué)意義(P=1.000,0.404)。經(jīng)Cp G ODN2006刺激后分泌IL-10、TGF-β的CD19+CD24highCD38high Breg細(xì)胞比例(10.13%±12.19%,7.38%±2.98%)與CD19+CD24highCD27+Breg(9.88%±6.48%,9.03%±3.75%)相比差異均無(wú)統(tǒng)計(jì)學(xué)意義(P=0.421,0.763)。CD19+CD24highCD38high Breg與CD19+CD24highCD27+Breg相比CD80表達(dá)水平差異無(wú)統(tǒng)計(jì)學(xué)意義(90.01%±8.78%vs.83.62%±16.51%,P=0.113),CD19+CD24highCD38high Breg細(xì)胞CD80表達(dá)水平高于非CD19+CD24highCD38high細(xì)胞(66.78%±17.32%,P=0.000),CD19+CD24highCD27+Breg細(xì)胞CD80表達(dá)水平與非CD19+CD24highCD27+細(xì)胞相比差異無(wú)統(tǒng)計(jì)學(xué)意義(84.42%±16.89%,P=0.690)。CD19+CD24highCD38high Breg與CD19+CD24highCD27+Breg相比CD86表達(dá)水平差異無(wú)統(tǒng)計(jì)學(xué)意義(89.31%±11.00%vs.89.49%±10.87%,P=0.515),CD19+CD24highCD38high Breg細(xì)胞CD86表達(dá)水平高于非CD19+CD24highCD38high細(xì)胞(85.37%±13.64%,P=0.000),CD19+CD24highCD27+Breg細(xì)胞CD86表達(dá)水平與非CD19+CD24highCD27+細(xì)胞相比差異無(wú)統(tǒng)計(jì)學(xué)意義(89.63%±10.74%,P=0.546)。結(jié)論:在正常人外周血單個(gè)核細(xì)胞中CD19+CD24highCD27+Breg的比例高于CD19+CD24highCD38high Breg。CD19+CD24highCD27+Breg凋亡水平高于非CD19+CD24highCD27+細(xì)胞。CD19+CD24highCD38high Breg增殖水平高于非CD19+CD24highCD38high細(xì)胞。CD19+CD24highCD38high Breg與CD19+CD24highCD27+Breg細(xì)胞BAFF-R、TACI、BCMA的表達(dá)及結(jié)合的BAFF、APRIL均無(wú)差異。CD19+CD24highCD38high Breg細(xì)胞BAFF-R、TACI的表達(dá)高于非CD19+CD24highCD38high細(xì)胞。CD19+CD24highCD38high Breg結(jié)合APRIL的水平高于非CD19+CD24highCD38high細(xì)胞。CD19+CD24highCD38high Breg細(xì)胞Tim-3表達(dá)水平高于CD19+CD24highCD27+Breg,并且二者均高于非Breg細(xì)胞。CD19+CD24highCD38high Breg與CD19CD24CD27Breg分泌IL-10、TGF-β的水平無(wú)差異。CD19+CD24highCD38high Breg與CD19+CD24highCD27+Breg均表達(dá)CD20。CD19+CD24highCD38high Breg細(xì)胞CD80、CD86表達(dá)水平高于非CD19+CD24highCD38high細(xì)胞。二、c GVHD患者CD19+CD24highCD38high及CD19+CD24highCD27+調(diào)節(jié)性B細(xì)胞數(shù)量變化及機(jī)制研究目的:探討異基因造血干細(xì)胞移植后c GVHD患者CD19+CD24highCD38high、CD19+CD24highCD27+調(diào)節(jié)性B細(xì)胞數(shù)量變化及相關(guān)機(jī)制。方法:流式細(xì)胞儀檢測(cè)輕-中度cGVHD患者、重度cGVHD患者、無(wú)cGVHD患者、免疫耐受者及健康志愿者外周血單個(gè)核細(xì)胞中CD19+CD24highCD38high、CD19+CD24highCD27+Breg細(xì)胞的比例及其凋亡、增殖、BAFF-R、TACI、BCMA、結(jié)合的BAFF及APRIL水平。酶聯(lián)免疫吸附試驗(yàn)(ELISA)測(cè)定各組患者血漿中BAFF、APRIL水平。依據(jù)血常規(guī)淋巴細(xì)胞計(jì)數(shù)及流式細(xì)胞儀檢測(cè)CD19+CD24highCD38high及CD19+CD24highCD27+Breg細(xì)胞的比例計(jì)數(shù)其絕對(duì)數(shù)。進(jìn)行各組間比較。結(jié)果:輕-中度c GVHD組B細(xì)胞絕對(duì)數(shù)[(3.83±2.20)×107/L]、CD19+CD24highCD38high Breg細(xì)胞絕對(duì)數(shù)[(13.31±13.53)×102/ml]、CD19+CD24highCD27+Breg細(xì)胞絕對(duì)數(shù)[(27.68±32.88)×102/ml]、CD19+CD24highCD38high Breg細(xì)胞比例(3.45%±1.75%)、CD19+CD24highCD27+Breg細(xì)胞比例(2.43%±1.42%)均低于無(wú)c GVHD組的(10.85±10.40)×107/L、(87.36±106.40)×102/ml、(57.59±61.85)×102/ml、6.26%±3.23%、5.06%±3.48%(P0.05)。輕-中度c GVHD組CD19+CD24highCD38high Breg細(xì)胞凋亡(48.40%±19.15%)、血漿BAFF水平[(2877.90±248.76)ng/L]、CD19+CD24highCD38high Breg細(xì)胞結(jié)合的BAFF水平(67.84%±19.12%)均高于無(wú)c GVHD組的22.23%±12.05%、(2495.60±386.78)ng/L、60.76%±18.90%(P0.05)。重度c GVHD組CD19+CD24highCD38high Breg細(xì)胞凋亡(72.34%±19.20%)、血漿BAFF水平[(3171.60±328.50)ng/L]、血漿BAFF/CD19+CD24highCD38high Breg細(xì)胞數(shù)的比值(15756.00±25144.61)、血漿BAFF/CD19+CD24highCD27+Breg細(xì)胞數(shù)的比值(8103.10±12623.27)、血漿APRIL/CD19+CD24highCD38high Breg細(xì)胞數(shù)的比值(16.35±32.03)、血漿APRIL/CD19+CD24highCD27+Breg細(xì)胞數(shù)的比值(8.53±12.05)、CD19+CD24highCD38high Breg細(xì)胞TACI表達(dá)水平(93.36%±9.76%)、CD19+CD24highCD38high Breg細(xì)胞結(jié)合的BAFF水平(79.12%±19.62%)、CD19+CD24highCD27+Breg細(xì)胞結(jié)合的BAFF水平(79.27%±18.57%)、CD19+CD24highCD38high Breg細(xì)胞上結(jié)合的APRIL水平(87.64%±23.69%)均高于無(wú)c GVHD組(P0.05)。重度c GVHD組B細(xì)胞絕對(duì)數(shù)[(2.58±3.75)×107/L]、CD19+CD24highCD38high Breg細(xì)胞絕對(duì)數(shù)[(2.97±5.89)×102/ml]、CD19+CD24highCD27+Breg細(xì)胞絕對(duì)數(shù)[(7.24±11.27)×102/ml]、CD19+CD24highCD38high Breg細(xì)胞比例(0.70%±0.40%)、CD19+CD24highCD27+Breg細(xì)胞比例(2.22%±0.87%)、CD19+CD24highCD38high Breg細(xì)胞增殖水平(2.02%±1.68%)、CD19+CD24highCD27+Breg細(xì)胞增殖(4.09%±2.44%)均低于無(wú)c GVHD組(P0.05)。重度c GVHD組CD19+CD24highCD38high Breg細(xì)胞比例、CD19+CD24highCD38high Breg細(xì)胞增殖水平均低于輕-中度c GVHD組(P0.05)。重度c GVHD組CD19+CD24highCD38high Breg細(xì)胞凋亡、血漿BAFF水平、血漿BAFF/CD19+CD24highCD38high Breg細(xì)胞數(shù)的比值、血漿BAFF/CD19+CD24highCD27+Breg細(xì)胞數(shù)的比值、血漿APRIL/CD19+CD24highCD38high Breg細(xì)胞數(shù)的比值、血漿APRIL/CD19+CD24highCD27+Breg細(xì)胞數(shù)的比值、CD19+CD24highCD38high Breg細(xì)胞上結(jié)合的BAFF水平、CD19+CD24highCD27+Breg細(xì)胞結(jié)合的BAFF水平均高于輕-中度c GVHD組(P0.05)。免疫耐受組B細(xì)胞絕對(duì)數(shù)[(13.30±15.84)×107/L]、CD19+CD24highCD38high Breg細(xì)胞絕對(duì)數(shù)[(168.05±220.05)×102/ml]、CD19+CD24highCD38high Breg細(xì)胞比例(11.40%±7.94%)、CD19+CD24highCD27+Breg細(xì)胞凋亡(47.91%±20.39%)、CD19+CD24highCD38high Breg細(xì)胞增殖(33.75%±13.47%)、血漿BAFF水平[(3152.80±752.48)ng/L]、血漿APRIL水平[(87.68±19.32)ng/L]、CD19+CD24highCD38high Breg細(xì)胞上結(jié)合的BAFF水平(68.16%±17.46%)、CD19+CD24highCD38high Breg細(xì)胞上結(jié)合的APRIL水平(81.89%±21.98%)均高于正常對(duì)照組的(4.68±2.96)×107/L、(27.48±24.99)×102/ml、5.88%±3.18%、28.84%±18.33%、21.46%±11.88%、(2218.80±229.32)ng/L、(69.83±10.27)ng/L、55.24%±17.46%、61.95%±31.66%(P0.05)。免疫耐受組CD19+CD24highCD27+Breg細(xì)胞絕對(duì)數(shù)[(42.11±33.25)×102/ml]、CD19+CD24highCD27+Breg細(xì)胞比例(4.14%±2.21%)、CD19+CD24highCD38high Breg細(xì)胞凋亡(15.18%±14.48%)、CD19+CD24highCD27+Breg細(xì)胞增殖(7.01%±5.62%)均低于正常對(duì)照組的(90.48±57.31)×102/ml、14.10%±9.47%、28.87%±14.82%、17.26%±13.18%(P0.05)。無(wú)c GVHD組B細(xì)胞絕對(duì)數(shù)、CD19+CD24highCD27+Breg細(xì)胞凋亡(54.49%±21.29%)、血漿APRIL水平、CD19+CD24highCD38high Breg細(xì)胞上結(jié)合的BAFF水平、CD19+CD24highCD38high Breg細(xì)胞上結(jié)合的APRIL水平、CD19+CD24highCD27+Breg細(xì)胞上結(jié)合的APRIL水平均高于正常對(duì)照組(P0.05)。無(wú)c GVHD組CD19+CD24highCD27+Breg細(xì)胞絕對(duì)數(shù)、CD19+CD24highCD27+Breg細(xì)胞比例、CD19+CD24highCD38high Breg細(xì)胞凋亡低于正常對(duì)照組(P0.05)。免疫耐受組CD19+CD24highCD38high Breg細(xì)胞絕對(duì)數(shù)、CD19+CD24highCD38high Breg細(xì)胞比例、血漿BAFF水平均高于無(wú)c GVHD組(P0.05)。免疫耐受組CD19+CD24highCD27+Breg細(xì)胞TACI表達(dá)水平(58.50%±28.08%)低于無(wú)c GVHD組的78.18%±28.75%(P0.05)。各組間CD19+CD24highCD38high Breg、CD19+CD24highCD27+Breg細(xì)胞BAFF-R、BCMA表達(dá)水平無(wú)差異(P0.05)。結(jié)論:異基因造血干細(xì)胞移植后c GVHD患者同無(wú)c GVHD者相比CD19+CD24highCD38high Breg、CD19+CD24highCD27+Breg細(xì)胞數(shù)量減低,且在重度c GVHD患者中CD19+CD24highCD38high Breg數(shù)量低于輕-中度c GVHD。在免疫耐受者中CD19+CD24highCD38high Breg數(shù)量較正常對(duì)照升高,但CD19+CD24highCD27+Breg細(xì)胞數(shù)量較正常對(duì)照減低。Breg細(xì)胞數(shù)量的變化與BAFF、APRIL及其受體變化所致凋亡和增殖水平的變化有關(guān)。三、c GVHD患者CD19+CD24highCD38high及CD19+CD24highCD27+調(diào)節(jié)性B細(xì)胞功能變化及機(jī)制研究目的:探討異基因造血干細(xì)胞移植后c GVHD患者CD19+CD24highCD38high、CD19+CD24highCD27+調(diào)節(jié)性B細(xì)胞功能變化及相關(guān)機(jī)制。方法:流式細(xì)胞儀檢測(cè)輕-中度c GVHD患者、重度c GVHD患者、無(wú)c GVHD患者、免疫耐受者及健康志愿者外周血單個(gè)核細(xì)胞中CD19+CD24highCD38high及CD19+CD24highCD27+Breg細(xì)胞分別經(jīng)CD40L及Cp G ODN2006刺激后分泌IL-10、TGF-β水平,同時(shí)檢測(cè)STAT3磷酸化(p STAT3)、My D88、CD40、TLR9、CD80、CD86及Tim-3水平,并進(jìn)行各組間比較。結(jié)果:經(jīng)CD40L刺激后輕-中度cGVHD、重度c GVHD患者CD19CD24CD38Breg細(xì)胞分泌IL-10的水平(2.32%±0.42%、0.56%±0.54%)均低于無(wú)c GVHD者(5.88%±3.11%)(P0.05),TGF-β水平各組間無(wú)差異;重度c GVHD患者CD19+CD24highCD27+Breg細(xì)胞分泌IL-10的水平(2.02%±1.90%)低于無(wú)c GVHD者(4.94%±3.81%)(P0.05),TGF-β水平各組間無(wú)差異。經(jīng)Cp G ODN2006刺激后CD19+CD24highCD38high Breg細(xì)胞分泌IL-10、TGF-β的水平均無(wú)差異;輕-中度c GVHD、重度c GVHD患者CD19+CD24highCD27+Breg細(xì)胞分泌IL-10的水平(4.02%±1.91%、1.69%±1.25%)均低于無(wú)c GVHD者(8.80%±5.98%)(P0.05),TGF-β水平各組間無(wú)差異。輕-中度c GVHD、重度c GVHD患者CD19+CD24highCD38high Breg細(xì)胞p STAT3水平(6.48%±10.20%、3.06%±4.80%)均低于無(wú)c GVHD者(14.79%±7.05%)(P0.05);My D88水平各組間無(wú)差異。重度c GVHD患者CD19+CD24highCD27+Breg細(xì)胞p STAT3、My D88水平(3.31%±2.09%,41.31%±29.52%)均低于無(wú)c GVHD者(27.98±12.65,69.41%±24.09%)(P0.05)。重度c GVHD患者CD19+CD24highCD38high、CD19+CD24highCD27+Breg細(xì)胞Tim-3水平(2.07%±0.58%、2.59%±2.44%)均低于無(wú)c GVHD者(11.35%±9.72%,16.34%±22.52%)(P0.05)。免疫耐受者CD19+CD24highCD27+Breg細(xì)胞Tim-3水平(23.49%±23.19%)高于正常對(duì)照(6.91%±5.88%)(P0.05)。CD19+CD24highCD38high、CD19+CD24highCD27+Breg細(xì)胞CD40、TLR9、CD80、CD86水平各組間均無(wú)差異。結(jié)論:異基因造血干細(xì)胞移植后cGVHD患者與無(wú)cGVHD者相比CD19+CD24highCD38high、CD19+CD24highCD27+Breg細(xì)胞分泌IL-10的功能減弱,分泌TGF-β的功能無(wú)異常。CD19+CD24highCD38high Breg功能的減弱與CD40介導(dǎo)的STAT3信號(hào)轉(zhuǎn)導(dǎo)通路上p STAT3水平減低有關(guān)。CD19+CD24highCD27+Breg分泌IL-10的功能的減弱與CD40介導(dǎo)的STAT3信號(hào)轉(zhuǎn)導(dǎo)通路上p STAT3水平減低及TLR9介導(dǎo)的My D88信號(hào)轉(zhuǎn)導(dǎo)通路上My D88水平減低均有關(guān)。c GVHD患者與無(wú)c GVHD者相比CD19+CD24highCD38high、CD19+CD24highCD27+Breg細(xì)胞Tim-3表達(dá)減低,而在免疫耐受者CD19+CD24highCD27+Breg細(xì)胞Tim-3表達(dá)較正常對(duì)照升高。四、對(duì)c GVHD具有生物標(biāo)記意義的B細(xì)胞相關(guān)基因篩選目的:篩選對(duì)cGVHD具有生物標(biāo)記意義的B細(xì)胞相關(guān)基因。方法:利用基因芯片方法分別對(duì)輕-中度cGVHD患者、重度cGVHD患者、無(wú)c GVHD患者、免疫耐受者及健康志愿者外周血單個(gè)核細(xì)胞的基因表達(dá)譜進(jìn)行檢測(cè),進(jìn)行組間比較,篩選出與B細(xì)胞相關(guān)的差異表達(dá)基因。應(yīng)用熒光定量PCR對(duì)篩選出的差異表達(dá)基因進(jìn)行驗(yàn)證。結(jié)果:基因芯片結(jié)果顯示cGVHD患者與無(wú)c GVHD患者相比共有284條表達(dá)差異基因,其中與B細(xì)胞相關(guān)的有5條,分別為CDKN2A、SOX4、ZBTB32、CD70、IL21R。免疫耐受患者與無(wú)c GVHD患者相比共有800條表達(dá)差異基因,其中與B細(xì)胞相關(guān)的有3條,分別為NFAM1、CD27、BST1。應(yīng)用熒光定量PCR對(duì)基因芯片篩選出的表達(dá)差異基因進(jìn)行驗(yàn)證,結(jié)果顯示c GVHD患者與無(wú)c GVHD患者相比CDKN2A基因的表達(dá)水平降低(P=0.001)。免疫耐受患者與無(wú)c GVHD患者相比CD27基因的表達(dá)水平升高(P=0.038),而BST1基因的表達(dá)水平減低(P=0.022)結(jié)論:c GVHD患者與無(wú)c GVHD患者相比CDKN2A基因的表達(dá)水平降低。免疫耐受患者與無(wú)c GVHD患者相比CD27基因的表達(dá)水平升高,而BST1基因的表達(dá)水平減低。這些基因的變化有望成為具有潛在生物標(biāo)記意義的指標(biāo)用于指導(dǎo)臨床工作。
[Abstract]:......
【學(xué)位授予單位】：蘇州大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2015
【分類號(hào)】：R457.7

【參考文獻(xiàn)】

相關(guān)期刊論文 前3條

1 彭碧云;唐曉文;;異基因活化的NK細(xì)胞與HLA全相合同胞造血干細(xì)胞移植預(yù)后的關(guān)系[J];中國(guó)實(shí)驗(yàn)血液學(xué)雜志;2010年03期

2 張玲玲;魏偉;;BAFF/BAFF-R通過PI3K/Akt/mTOR信號(hào)轉(zhuǎn)導(dǎo)通路調(diào)節(jié)B淋巴細(xì)胞功能在類風(fēng)濕關(guān)節(jié)炎發(fā)病機(jī)制中的意義[J];中國(guó)藥理學(xué)通報(bào);2010年07期

3 周茂華;王春苗;龔彩平;羅盈;張敏;;慢性移植物抗宿主病患者外周血NK細(xì)胞、NKT細(xì)胞的檢測(cè)及意義[J];中國(guó)實(shí)驗(yàn)血液學(xué)雜志;2012年05期

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