GP210与原发性胆汁性肝硬化患者TLR3表达的关系及其临床意义被引量：4

Correlation of GP210 with Expression of TLR3 in Primary Biliary Cirrhosis

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摘要目的探讨原发性胆汁性肝硬化(primary biliary cirrhosis,PBC)患者外周血细胞TLR3的表达及其在GP210抗体阳性和阴性患者之间的表达差异。方法选择初次确诊的PBC患者65例,其中男15例,女50例。GP210抗体阳性患者21例,阴性患者44例。对照组选择性别和年龄相匹配的慢性乙肝(chronic hepatitis B,CHB)患者22例。对所有患者分离外周血单个核细胞(peripheral blood monuclear cell,PBMC),抽提总RNA,定量PCR分析其TLR3的mRNA表达水平。分别以anti-CD3、anti-CD4、anti-CD8和anti-TLR3抗体对PBMC进行染色,流式细胞术分析各细胞亚群中TLR3的表达情况。结果 PBC组患者血清碱性磷酸酶(ALP)显著高于CHB组(P=0.002),而且GP210阳性PBC患者ALP高于阴性患者(P=0.004)。PCR结果表明,PBC组PBMC中TLR3的mRNA表达量显著高于CHB组(P=0.01),而且PBC组内GP210阳性患者表达高于阴性患者的表达水平(P<0.001)。流式细胞术分析结果发现,PBC组PBMC、CD3+、CD4+、CD8+T细胞表面的TLR3表达量均显著高于CHB组,差异有统计学意义(P<0.05);其中PBC组GP210阳性患者PBMC、CD3+和CD8+T细胞表达量较GP210患者均显著升高,差异有统计学意义(P<0.05),而CD4+T细胞无显著差异(P>0.05)。结论 GP210阳性PBC患者中PBMC和T细胞表面TLR3的基因和蛋白表达水平均高于GP210阴性患者,TLR3的表达差异对于PBC的诊断和预后判断具有一定临床价值。 Objective To investigate the expression of TLR3 in peripheral blood of patients with primary biliary cirrhosis（PBC）and its difference in GP210 positive and negative patients.Methods 65 patients with PBC were involved in this study,male 15,female 50.21 patients with GP210 positive and 44 patients with GP210 negative.peripheral blood monuclear cells（PBMC）were isolated and total RNA was extracted for TLR3 mRNA determination.PBMC were stained with anti-CD3,anti-CD4,anti-CD8 and anti-TLR3,and assayed by flow cytometry.Results Higher levels of alkaline phosphatase（ALP）in PBC than that in CHB were found（P=0.002）.GP210 positive PBC patients with higher levels of ALP than those of negative patients（P=0.004）.Results of PCR showed that TLR3 mRNA in patients with PBC was higher than those with CHB（P=0.01）.Furthermore,GP210 positive patients express moreTLR3 mRNA than negative patients（P〈0.001）.Results of flow cytometry showed that TLR3 in PBMC,CD3＋,CD4＋and CD8＋T cells in patients with PBC were higher than that in CHB patients（P〈0.05）.TLR3 in PBMC,CD3＋and CD8＋ T cells in GP210 positive patients were higher than those in negative patients（P〈0.05）,however,no clinical significance was found in CD4＋ T cells（P〉0.05）.Conclusion mRNA and protein levels of TLR3 in PBMC and T cells of GP210 positive patients were significantly higher than that in GP210 negative patients,which maybe in diagnosis and prognosis in PBC.

作者杨鸿林沈国荣沈昊钮丽萍钱建平龚燕萍蒋廷旺殷雄

机构地区江苏省吴江区第一人民医院检验科江苏省常熟市医学检验所

出处《中国实验诊断学》 2016年第5期775-779,共5页 Chinese Journal of Laboratory Diagnosis

基金国家高技术研究发展计划(863计划子任务:2014AA022304) 常熟市科技发展计划社会发展项目(CS201218 CS201313 CS201417)

关键词原发性胆汁性肝硬化 GP210 TOLL样受体3 T细胞 primary biliary cirrhosis GP210 TLR3 T cells

分类号 R575.2 [医药卫生—消化系统]

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参考文献12

1蒋廷旺,韩志君,熊怀民,盛建华,张红星,龚燕萍,仲人前.IL-27诱导原发性胆汁性肝硬化患者CD4^＋T细胞增殖分化作用机制研究[J].中华微生物学和免疫学杂志,2011,31(11):1023-1026. 被引量：4
2Bandin O, Courvalin JC,Poupon R, et al. Specificity and sensitivity of gp210 autoantihodies detected using an enzyme linked immu nosorbent assay and a synthetic polypeptide in the diagnosis of primary hiliary cirrhosis[J]. Hepatology, 1996,23(5) :1020.
3Muratori P, Muratori L, Ferrari R, et al. Characterization and clin- ical impact of antinuclear antibodies in primary biliary cirrhosis [J]. Am J Gastroenterol,2003,98(2) :431.
4Harte MT, Haga IR, Maloney G, et al. The poxvirus protein A52R targets Toll-like receptor signaling complexes to suppress host defense[J]. J Exp Meal,2003,197(3):343.
5Tabiasco J, Devevre E, Ruler N, et al. Human effector CD8 + T lymphocytes express TLR3 as a functional coreceptor[J]. J Im- munol, 2006,177(12) : 8708.
6Marshall M, Kaplan M, Eric Gershwin. Primary biliary cirrhosis [J]. N Engl J Med,2005,353(12):1261.
7Horwitz MS, Bradley LM, Harbertson J, et al. Diabetes induced by Coxsackie virus:initiation by bystander damage and not molec- ular mimicry[J]. Nat Med, 1998,4(7) : 781.
8Lang KS,Recher M,Junt T, et al. Toll-like receptor engagement converts T cell autoreaetivity into overt autoimmune disease[J]. Nat Med,2005,11(2) :138.
9Chen S, Cheng A,Wang M. Innate sensing of viruses by pattern recognition receptors in birds[J]. Vet Res, 2013,44 : 82.
10Granito A1, Muratori P, Quarneti C, et al. Antinuclear antibodies as ancillary markers in primary biliary cirrhosis[J]. Expert Rev Mol Diagn,2012,12(1) :65.

二级参考文献13

1Kaplan MM,Gershwin ME.Primary biliary cirrhosis.N Engl J Med,2005,353(12):1261-1273.
2Liu J,Guan X,Ma X.Regulation of IL-27 p28 gene expression in macrophages through MyD88-and interferon-gamma-mediated pathways.J Exp Med,2007,204(1):141-152.
3Pflanz S,Timans JC,Cheung J,et al.IL-27,a heterodimeric cytokine composed of EBI3 and p28 protein,induces proliferation of naive CD4(+) T cells.Immunity,2002,16(6):779-790.
4Heathcote EJ.Management of primary biliary cirrhosis.The american association for the study of liver diseases practice guidelines.Hepatology,2000,31(4):1005-1013.
5Schmidt C,Giese T,Ludwig B,et al.Expression of interleukin12-related cytokine transcripts in inflammatory bowel disease:elevated interleukin-23p19 and interleukin-27p28 in Crohn's disease but not in ulcerative colitis.Inflamm Bowel Dis,2005,11 (1):16-23.
6Honda K,Nakamura K,Matsui N,et al.T helper 1-inducing property of IL-27/WSX-1 signaling is required for the induction of experimental colitis.Inflamm Bowel Dis,2005,11 (12):1044-1052.
7Goldberg R,Wildbaum G,Zohar Y,et al.Suppression of ongoing adjuvant-induced arthritis by neutralizing the function of the p28 subunit of IL-27.J Immunol,2004,173(2):1171-1178.
8Shimoda S,Van de Water J,Ansari A,et al.Identification and precursor frequency analysis of a common T cell epitope motif in mitochondrial autoantigens in primary biliary cirrhosis.J Clin Invest,1998,102(10):1831-1840.
9Harada K,Van de Water J,Leung PS,et al.In situ nucleic acid hybridization of cytokines in primary biliary cirrhosis:predominance of the Th1 subset.Hepatology,1997,25(4):791-796.
10Takeda A,Hamano S,Yamanaka A,et al.Cutting edge:role of IL-27/WSX-1 signaling for induction of T-bet through activation of STAT1 during initial Th1 commitment. J Immunol,2003,170(10):4886-4890.