补肾益髓胶囊对视神经脊髓炎谱系疾病患者缓解期PB、Breg、mB及Th细胞亚群的影响
|
摘要
目的:观察补肾益髓胶囊治疗缓解期神经脊髓炎谱系疾病(NMOSD)患者的临床疗效及其对外周血浆母细胞(PB)、调节性B细胞(Breg)、记忆性B细胞(mB)及CXCR5+辅助性T细胞(Th)表达的影响。方法:本研究纳入缓解期NMOSD患者22例,使用补肾益髓胶囊治疗3个月。通过对比患者服用药物前后扩展残疾状态量表(EDSS)评分、中医症状评分及PB、Breg、mB及Th细胞亚群分布变化,探讨补肾益髓胶囊治疗NMOSD患者的作用机制。结果:经补肾益髓胶囊干预后,缓解期NMOSD患者EDSS评分、中医症状评分明显下降(P<0.05,P<0.01);外周血mB及PB在B细胞中的亚群分布未见显著差异;Breg在B细胞亚群分布显著增加(P<0.05);CXCR5+Th细胞在T细胞亚群分布中具有减少趋势,但未见显著差异。结论:补肾益髓胶囊可以显著改善缓解期NMOSD患者的临床症状,这可能与其能够增加Breg细胞亚群分布相关。
Objective: To observe clinical efficacy of Bushen Yisui Capsule(BSYSC) of neuromyelitis optica spectrum disorders(NMOSD) during remission, and its effect on the subgroup of B cells, plasmablast(PB), regulatory B cells(Breg),memory B cells(mB) and CXCR5+ helper T cells(CXCR5+Th). Methods: A total of 22 NMOSD patients during remission with deficiency of kidney-liver yin syndrome were enrolled and treated with BSYSC for 3 months. Expanded disability status scale(EDSS) and Chinese traditional medicine symptom(TCMS) scores were assessed by cohort researchers. The subgroup of PB, Breg, mB and CXCR5+Th in the peripheral blood were detected using flow cytometry(FCM). Results: The EDSS score and TCMS score decreased after treatment(P<0.05, P<0.01). After treatment, serum subgroup of B, PB and mB didn't change significantly, but Breg portion were upregulated by treatment(P<0.05). The ratio of CXCR5+Th in CD4+ cells were downregulated by the treatment, but there was no significant difference before and after treatment. Conclusion: BSYSC could alleviate NMOSD symptoms through regulating Breg portion in peripheral blood.
Objective: To observe clinical efficacy of Bushen Yisui Capsule(BSYSC) of neuromyelitis optica spectrum disorders(NMOSD) during remission, and its effect on the subgroup of B cells, plasmablast(PB), regulatory B cells(Breg),memory B cells(mB) and CXCR5+ helper T cells(CXCR5+Th). Methods: A total of 22 NMOSD patients during remission with deficiency of kidney-liver yin syndrome were enrolled and treated with BSYSC for 3 months. Expanded disability status scale(EDSS) and Chinese traditional medicine symptom(TCMS) scores were assessed by cohort researchers. The subgroup of PB, Breg, mB and CXCR5+Th in the peripheral blood were detected using flow cytometry(FCM). Results: The EDSS score and TCMS score decreased after treatment(P<0.05, P<0.01). After treatment, serum subgroup of B, PB and mB didn't change significantly, but Breg portion were upregulated by treatment(P<0.05). The ratio of CXCR5+Th in CD4+ cells were downregulated by the treatment, but there was no significant difference before and after treatment. Conclusion: BSYSC could alleviate NMOSD symptoms through regulating Breg portion in peripheral blood.
引文
[1]Lennon V A,Wingerchuk D M,Kryzer T J,et al.A serum autoantibody marker of neuromyelitis optica:Distinction from multiple sclerosis.Lancet,2004,364(9451):2106-2112
[2]Takahashi T,Fujihara K,Nakashima I,et al.Anti-aquaporin-4antibody is involved in the pathogenesis of NMO:A study on antibody titre.Brain,2007,130(Pt 5):1235-1243
[3]Vaknin-Dembinsky A,Karussis D,Avichzer J,et al.NMO spectrum of disorders:A paradigm for astrocyte-targeting autoimmunity and its implications for MS and other CNS inflammatory diseases.J Autoimmun,2014,54:93-99
[4]Hao Z,Duncan G S,Seagal J,et al.Fas receptor expression in germinal-center B cells is essential for T and B lymphocyte homeostasis.Immunity,2008,29(4):615-627
[5]Khan T N,Wong E B,Soni C,et al.Prolonged apoptotic cell accumulation in germinal centers of Mer-deficient mice causes elevated B cell and CD4+Th cell responses leading to autoantibody production.J Immunol,2013,190(4):1433-1446
[6]Sellner J,Boggild M,Clanet M,et al.EFNS guidelines on diagnosis and management of neuromyelitis optica.Eur J Neurol,2010,17(8):1019-1032
[7]王苏.补肾益髓胶囊对视神经脊髓炎缓解期临床疗效及体液免疫功能的影响.北京:北京中医药大学,2015
[8]樊永平,胡蕊,鲍显慧,等.63例视神经脊髓炎患者临床特点和中医证型分布.中国中西医结合杂志,2013,33(3):322-325
[9]王苏,樊永平,张永超,等.不同中医证型视神经脊髓炎患者临床特点比较.环球中医药,2014,7(11):833-835
[10]王苏,樊永平,张永超,等.中医辨证论治对视神经脊髓炎年复发率影响的临床观察.中华中医药杂志,2014,29(12):3814-3816
[11]樊永平,陈克龙,尤昱中,等.补肾益髓胶囊治疗肝肾阴虚复发缓解型多发性硬化临床疗效观察.中华中医药杂志,2018,33(9):4220-4223
[12]Krumbholz M,Meinl E.B cells in MS and NMO:Pathogenesis and therapy.Semin Immunopathol.2014,36(3):339-350
[13]Fernández-Megía M J,Casanova-Estruch B,Pérez-Miralles F,et al.Clinical evaluation of rituximab treatment for neuromyelitis optica.Neurologia,2015,30(8):461-464
[14]Longoni G,Banwell B,Filippi M,et al.Rituximab as a first-line preventive treatment in pediatric NMOSDs:Preliminary results in 5children.Neurol Neuroimmunol Neuroinflamm,2014,1(4):e46
[15]Ligocki A J,Rounds W H,Cameron E M,et al.Expansion of CD27high plasmablasts in transverse myelitis patients that utilize VH4 and JH6 genes and undergo extensive somatic hypermutation.Genes Immun,2013,14(5):291-301
[16]Chihara N,Aranami T,Sato W,et al.Interleukin 6 signaling promotes anti-aquaporin 4 autoantibody production from plasmablasts in neuromyelitis optica.Proc Natl Acad Sci USA,2011,108(9):3701-3706
[17]Quan C,Yu H,Qiao J,et al.Impaired regulatory function and enhanced intrathecal activation of B cells in neuromyelitis optica:Distinct from multiple sclerosis.Mult Scler,2013,19(3):289-298
[18]Morita R,Schmitt N,Bentebibel S E,et al.Human blood CXCR5(+)CD4(+)T cells are counterparts of T follicular cells and contain specific subsets that differentially support antibody secretion.Immunity,2011,34(1):108-121
[2]Takahashi T,Fujihara K,Nakashima I,et al.Anti-aquaporin-4antibody is involved in the pathogenesis of NMO:A study on antibody titre.Brain,2007,130(Pt 5):1235-1243
[3]Vaknin-Dembinsky A,Karussis D,Avichzer J,et al.NMO spectrum of disorders:A paradigm for astrocyte-targeting autoimmunity and its implications for MS and other CNS inflammatory diseases.J Autoimmun,2014,54:93-99
[4]Hao Z,Duncan G S,Seagal J,et al.Fas receptor expression in germinal-center B cells is essential for T and B lymphocyte homeostasis.Immunity,2008,29(4):615-627
[5]Khan T N,Wong E B,Soni C,et al.Prolonged apoptotic cell accumulation in germinal centers of Mer-deficient mice causes elevated B cell and CD4+Th cell responses leading to autoantibody production.J Immunol,2013,190(4):1433-1446
[6]Sellner J,Boggild M,Clanet M,et al.EFNS guidelines on diagnosis and management of neuromyelitis optica.Eur J Neurol,2010,17(8):1019-1032
[7]王苏.补肾益髓胶囊对视神经脊髓炎缓解期临床疗效及体液免疫功能的影响.北京:北京中医药大学,2015
[8]樊永平,胡蕊,鲍显慧,等.63例视神经脊髓炎患者临床特点和中医证型分布.中国中西医结合杂志,2013,33(3):322-325
[9]王苏,樊永平,张永超,等.不同中医证型视神经脊髓炎患者临床特点比较.环球中医药,2014,7(11):833-835
[10]王苏,樊永平,张永超,等.中医辨证论治对视神经脊髓炎年复发率影响的临床观察.中华中医药杂志,2014,29(12):3814-3816
[11]樊永平,陈克龙,尤昱中,等.补肾益髓胶囊治疗肝肾阴虚复发缓解型多发性硬化临床疗效观察.中华中医药杂志,2018,33(9):4220-4223
[12]Krumbholz M,Meinl E.B cells in MS and NMO:Pathogenesis and therapy.Semin Immunopathol.2014,36(3):339-350
[13]Fernández-Megía M J,Casanova-Estruch B,Pérez-Miralles F,et al.Clinical evaluation of rituximab treatment for neuromyelitis optica.Neurologia,2015,30(8):461-464
[14]Longoni G,Banwell B,Filippi M,et al.Rituximab as a first-line preventive treatment in pediatric NMOSDs:Preliminary results in 5children.Neurol Neuroimmunol Neuroinflamm,2014,1(4):e46
[15]Ligocki A J,Rounds W H,Cameron E M,et al.Expansion of CD27high plasmablasts in transverse myelitis patients that utilize VH4 and JH6 genes and undergo extensive somatic hypermutation.Genes Immun,2013,14(5):291-301
[16]Chihara N,Aranami T,Sato W,et al.Interleukin 6 signaling promotes anti-aquaporin 4 autoantibody production from plasmablasts in neuromyelitis optica.Proc Natl Acad Sci USA,2011,108(9):3701-3706
[17]Quan C,Yu H,Qiao J,et al.Impaired regulatory function and enhanced intrathecal activation of B cells in neuromyelitis optica:Distinct from multiple sclerosis.Mult Scler,2013,19(3):289-298
[18]Morita R,Schmitt N,Bentebibel S E,et al.Human blood CXCR5(+)CD4(+)T cells are counterparts of T follicular cells and contain specific subsets that differentially support antibody secretion.Immunity,2011,34(1):108-121