多发性硬化患者外周血T细胞PD1表达的研究
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摘要
目的探讨程序性死亡分子1(PD1)在多发性硬化(MS)患者外周血T细胞上的表达及临床意义。方法急性发作期的复发-缓解型MS患者和健康者各39例,采用酶联免疫法检测血浆IL-17、IL-23的水平变化,流式细胞仪检测外周血T细胞上PD1表达(MFI和百分率),对MS患者进行扩展残疾状况评分量表(EDSS)评分和头颅MRI增强病灶数目的评估。结果 MS患者治疗前较健康者PD1表达(MFI和百分率)水平、IL-17和IL-23水平、EDSS评分、头颅MRI增强病灶数目均较高(P<0.05);MS患者治疗前比治疗后PD1表达(MFI和百分率)水平、IL-17和IL-23水平、EDSS评分均较高(P<0.05)。MS患者治疗前PD1表达(MFI和百分率)水平分别与IL-17和IL-23水平、EDSS评分、头颅MRI增强病灶数目均呈正相关(P<0.05)。结论 MS患者急性发作期外周血T细胞表达PD1升高,且与IL-17和IL-23炎症因子水平具有相关性,可能在MS严重程度和疾病进展起重要作用。
To explore the expression and clinical significance of programmed death molecule 1(PD1) in peripheral blood T cells of patients with multiple sclerosis(MS), 39 cases of relapse-remission MS patients in acute episode were recruited and 39 healthy individuals were treated as controls. Changes in plasma IL-17 and IL-23 levels were detected by enzyme-linked immunoassay, and PD1 expression(MFI and percentage) on peripheral blood T cells was detected by flow cytometry(FCM). Furthermore, MS patients were evaluated with the Expanded Disability Status Scale(EDSS) score and the number of cranial lesions was observed by enhanced MRI. Data showed that PD1 expression(MFI and percentage), IL-17 and IL-23 levels, EDSS score and the number of cranial lesions were all higher in untreated MS patients, as compared with healthy controls(P<0.05); the expression levels of PD1(MFI and percentage), IL-17 and IL-23 levels, and EDSS scores were higher in MS patients before treatment compared with post-treatment(P<0.05). Before treatment, PD1 expression(MFI and percentage) in MS patients were positively correlated with IL-17 and IL-23 levels, EDSS score and the number of cranial lesions, respectively(P<0.05). Taken together, PD1 expression in peripheral blood T cells is increased in MS patients during acute onset, and is correlated with IL-17 and IL-23 inflammatory cytokines, thus may play an important role in MS severity and disease progression.
To explore the expression and clinical significance of programmed death molecule 1(PD1) in peripheral blood T cells of patients with multiple sclerosis(MS), 39 cases of relapse-remission MS patients in acute episode were recruited and 39 healthy individuals were treated as controls. Changes in plasma IL-17 and IL-23 levels were detected by enzyme-linked immunoassay, and PD1 expression(MFI and percentage) on peripheral blood T cells was detected by flow cytometry(FCM). Furthermore, MS patients were evaluated with the Expanded Disability Status Scale(EDSS) score and the number of cranial lesions was observed by enhanced MRI. Data showed that PD1 expression(MFI and percentage), IL-17 and IL-23 levels, EDSS score and the number of cranial lesions were all higher in untreated MS patients, as compared with healthy controls(P<0.05); the expression levels of PD1(MFI and percentage), IL-17 and IL-23 levels, and EDSS scores were higher in MS patients before treatment compared with post-treatment(P<0.05). Before treatment, PD1 expression(MFI and percentage) in MS patients were positively correlated with IL-17 and IL-23 levels, EDSS score and the number of cranial lesions, respectively(P<0.05). Taken together, PD1 expression in peripheral blood T cells is increased in MS patients during acute onset, and is correlated with IL-17 and IL-23 inflammatory cytokines, thus may play an important role in MS severity and disease progression.
引文
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[9]World Medical Association.Declaration of Helsinki.Ethical principles for medical research involving human subjects[J].J Indian MedAssoc,2009,107(6):403-405.
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[11]Brahmachari S,Pahan K.Roleofcy tokinep 40 family in multiple sclerosis[J].Minerva Med,2008,99(2):105-118.
[12]Matusevicius D,Kivis P,He B,et al.Interleukin-17 m RNAexpression in blood and CSF mononuclear cell sis augmented in multiple sclerosis[J].Mult Scler,1999,5(2):101-104.
[13]Sonobe Y,Jin S,Wang J,et al.Chronological changes of CD4(+)and CD8(+)T cell subsets in the experimental experimental autoimmune encephalomyelitis,a mouse model of multiple sclerosis[J].Tohoku J Exp Med,2007,213(4):329-339.
[14]David JS,Durand M,Levrat A,et al.Correlation between laboratory coagulation testing and thromboelastometry is modified during management of trauma patients[J].JTrauma Acute Care Surg,2016,81(2):319-327.
[15]Campbell JE,Aden JK,Cap AP.Acute traumatic coagulopathy:Whole blood thrombelastography measures the tip of the iceberg[J].J Trauma Acute Care Surg,2015,78(5):955-961.
[16]Salama AD,Chitnis T,Imitola J,et al.Critical role of the programmed death-1(PD-1)pathway in regulation of experimental autoimmune encephalomyelitis[J].J Exper Med,2003,198(1):71-76.
[17]Carter LL,Leach MW.PD-1/PD-L1,interactions regulate the severity of experimental autoimmune encephalomyelitis[J].J Neuroimmunol,2007,182(1/2):124-34.
[18]Order S,Leder C,Mittelbronn M,et al.B7-H1 restricts neuroantigen-specific T cell responses and confines inflammatory CNS damage:Implications for the lesion pathogenesis of multiple sclerosis[J].Eur J Immunol,2008,38(6):1734-1744.
[19]Ho PP,Steinman L.Obeticholic acid,a synthetic bile acid agonist of the farnesoid X receptor,attenuates experimental autoimmune encephalomyelitis[J].Proc Natl Acad Sci,2016,113(6):1600-1605.
[2]王娟,刘军权,陈复兴,等.β-谷甾醇对人共刺激细胞杀伤胃癌SGC-7901细胞的影响及其机制的探讨[J].免疫学杂志,2014,30(7):578-584.
[3]Badawi AH,Kiptoo P,Siahaan TJ.Immune tolerance induction against experimental autoimmune encephalomyelitis(EAE)using a new PLP-B7APconjugate that simultaneously targets B7/CD28costimulatorysignal and TCR/MHC-II signal[J].J Mult Scler,2015,2(1):79-81.
[4]黄自坤,李雪,罗忠勤,等.类风湿性关节炎外周血中性粒细胞PD-L1表达及意义[J].免疫学杂志,2017,33(7):586-590.
[5]曹青青.Breg、PD1、PDL1通过耐受性树突状细胞在实验性自身免疫性脑脊髓炎中的治疗作用及机制[D].吉林大学,2017.
[6]Kroner A,Mehling M,Hemmer B,et al.A PD-1polymorphism is associated with disease progression in multiple sclerosis[J].Ann Neurol,2005,58(1):50-57.
[7]Gajofatto A,Nourbakhsh B,Benedetti MD,et al.Performance of 2010 McDonald criteria and 2016MAGNIMS guidelines in the diagnosis of primary progressive multiple sclerosis[J].J Neurol Neurosurg Psychiatry,2017,9(22):316-322.
[8]中华医学会神经病学分会神经免疫学组,中国免疫学会神经免疫分会.多发性硬化诊断和治疗中国专家共识(2014版)[J].中华神经科杂志,2015,48(5):362-367.
[9]World Medical Association.Declaration of Helsinki.Ethical principles for medical research involving human subjects[J].J Indian MedAssoc,2009,107(6):403-405.
[10]Graber JJ,Allie SR,Mullen KM,et al.Interleukin-17 in transverse myelitis and multiple sclerosis[J].JNeuroimmunol,2008,196(1/2):124-132.
[11]Brahmachari S,Pahan K.Roleofcy tokinep 40 family in multiple sclerosis[J].Minerva Med,2008,99(2):105-118.
[12]Matusevicius D,Kivis P,He B,et al.Interleukin-17 m RNAexpression in blood and CSF mononuclear cell sis augmented in multiple sclerosis[J].Mult Scler,1999,5(2):101-104.
[13]Sonobe Y,Jin S,Wang J,et al.Chronological changes of CD4(+)and CD8(+)T cell subsets in the experimental experimental autoimmune encephalomyelitis,a mouse model of multiple sclerosis[J].Tohoku J Exp Med,2007,213(4):329-339.
[14]David JS,Durand M,Levrat A,et al.Correlation between laboratory coagulation testing and thromboelastometry is modified during management of trauma patients[J].JTrauma Acute Care Surg,2016,81(2):319-327.
[15]Campbell JE,Aden JK,Cap AP.Acute traumatic coagulopathy:Whole blood thrombelastography measures the tip of the iceberg[J].J Trauma Acute Care Surg,2015,78(5):955-961.
[16]Salama AD,Chitnis T,Imitola J,et al.Critical role of the programmed death-1(PD-1)pathway in regulation of experimental autoimmune encephalomyelitis[J].J Exper Med,2003,198(1):71-76.
[17]Carter LL,Leach MW.PD-1/PD-L1,interactions regulate the severity of experimental autoimmune encephalomyelitis[J].J Neuroimmunol,2007,182(1/2):124-34.
[18]Order S,Leder C,Mittelbronn M,et al.B7-H1 restricts neuroantigen-specific T cell responses and confines inflammatory CNS damage:Implications for the lesion pathogenesis of multiple sclerosis[J].Eur J Immunol,2008,38(6):1734-1744.
[19]Ho PP,Steinman L.Obeticholic acid,a synthetic bile acid agonist of the farnesoid X receptor,attenuates experimental autoimmune encephalomyelitis[J].Proc Natl Acad Sci,2016,113(6):1600-1605.