CD19+CD24~(high) CD38~(high)调节性B细胞及相关细胞因子在视神经脊髓炎谱系疾病患者外周血中的变化及意义
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摘要
目的检测NMOSD患者外周血中CD19~+CD24~(high)CD38~(high)Breg及其细胞因子IL-10、TGF-β水平,探讨CD19~+CD24~(high)CD38~(high)Breg、IL-10、TGF-β在NMOSD急性期的变化及可能作用;检测NMOSD患者外周血GFAP水平,结合EDSS评分,探讨GFAP与疾病严重程度的相关性。方法选取2016年12月-2018年1月就诊于河北医科大学第二医院神经内科NMOSD急性期患者27例为实验组,性别、年龄相匹配的20例健康人为对照组。入组的NMOSD患者进行EDSS评分、流式细胞术检测外周血CD19~+CD24~(high)CD38~(high)Breg数量,PCR法检测外周血IL-10、TGF-β、GFAP的mRNA水平,并与健康人比较。结果 NMOSD组CD19~+CD24~(high)CD38~(high)Breg水平较对照组下降,差异有统计学意义,CD19~+CD24~(high)CD38~(high)Breg与EDSS之间无线性关系。NMOSD组IL-10、TGF-β的mRNA水平较对照组下降,差异有统计学意义。NMOSD组GFAP水平较对照组升高,差异有统计学意义。GFAP与EDSS之间无线性关系。结论 CD19~+CD24~(high)CD38~(high)Breg在NMOSD急性期发病中数量和功能上均受损,血清GFAP水平增高,但不能反应复发患者疾病残疾程度。
Objective The levels of CD19~+CD24~(high)CD38~(high)Breg,IL-10 and TGF-beta in peripheral blood of patients with NMOSD were analyzed,and the role of CD19~+CD24~(high)CD38~(high)Breg in the acute phase of NMOSD was discussed. The level of GFAP in peripheral blood of NMOSD patients was detected and the correlation between GFAP and the severity of the disease was discussed with the EDSS score. Methods From December 2016 to 2018 01,27 patients in the acute phase of NMOSD in the Second Hospital of Hebei Medical University were selected as the experimental group,and 20 healthy persons matched for sex and age were selected as control group. The EDSS score and flow cytometry were used to detect the number of CD19~+CD24~(high)CD38~(high)Breg in peripheral blood of NMOSD patients. The levels of IL-10,TGF-and GFAP in peripheral blood were detected by PCR and compared with healthy persons. Results The level of CD19+CD24 high CD38 highBreg in group of NMOSD was lower than that in the control group,and the difference was statistically significant.There was no linear relationship between Bregs and EDSS score. The levels of IL-10 and TGF-beta in group of NMOSD were lower than that in the control group,and the difference was statistically significant. The level of GFAP in group of NMOSD was higher than that in the control group,and there was a significant difference between the two groups. There is no linear relationship between GFAP and EDSS. Conclusion CD19~+CD24~(high)CD38~(high)Breg was not only significantly reduced in the pathogenesis of NMOSD,but also significantly impaired in its function. The serum GFAP increased but it has no relationship with EDSS in relapsed NMOSD patients.
Objective The levels of CD19~+CD24~(high)CD38~(high)Breg,IL-10 and TGF-beta in peripheral blood of patients with NMOSD were analyzed,and the role of CD19~+CD24~(high)CD38~(high)Breg in the acute phase of NMOSD was discussed. The level of GFAP in peripheral blood of NMOSD patients was detected and the correlation between GFAP and the severity of the disease was discussed with the EDSS score. Methods From December 2016 to 2018 01,27 patients in the acute phase of NMOSD in the Second Hospital of Hebei Medical University were selected as the experimental group,and 20 healthy persons matched for sex and age were selected as control group. The EDSS score and flow cytometry were used to detect the number of CD19~+CD24~(high)CD38~(high)Breg in peripheral blood of NMOSD patients. The levels of IL-10,TGF-and GFAP in peripheral blood were detected by PCR and compared with healthy persons. Results The level of CD19+CD24 high CD38 highBreg in group of NMOSD was lower than that in the control group,and the difference was statistically significant.There was no linear relationship between Bregs and EDSS score. The levels of IL-10 and TGF-beta in group of NMOSD were lower than that in the control group,and the difference was statistically significant. The level of GFAP in group of NMOSD was higher than that in the control group,and there was a significant difference between the two groups. There is no linear relationship between GFAP and EDSS. Conclusion CD19~+CD24~(high)CD38~(high)Breg was not only significantly reduced in the pathogenesis of NMOSD,but also significantly impaired in its function. The serum GFAP increased but it has no relationship with EDSS in relapsed NMOSD patients.
引文
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[18]Song J,Xiao L,Du G,et al.The role of regulatory B cells(Bregs)in the Tregs-amplifying effect of Sirolimus[J].Int Immunopharmacol,2016,38:90-96.
[19]Lucchinetti CF,Guo Y,Popescu BF,et al.The pathology of an autoimmune astrocytopathy:lessons learned from neuromyelitis optica[J].Brain Pathol,2014,24(1):83-97.
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[3]Bukhari W,Prain KM,Waters P,et al.Incidence and prevalence of NMOSD in Australia and New Zealand[J].J Neurol Neurosurg Psychiatry,2017,88(8):632-638.
[4]韩冰,朱辉,刘晶瑶.AQP4与NMO-IgG在视神经脊髓炎谱系疾病发病机制中的作用[J].中风与神经疾病杂志,2017,34(11):1045-1046.
[5]Wingerchuk DM,Banwell B,Bennett JL,et al.International consensus diagnostic criteria for neuromyelitis optica spectrum disorders[J].Neurology,2015,85(2):177-189.
[6]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].J Autoimmun,2014,54:93-99.
[7]Liu Y,Mc Daniel JR,Khan S,et al.Antibodies encoded by FCRL4-bearing memory B cells preferentially recognize commensal microbial antigens[J].J Immunol,2018,200(12):3962-3969.
[8]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[J].Mult Scler,2013,19(3):289-298.
[9]Zhang R,Sage PT,Finn K,et al.B cells drive autoimmunity in mice with CD28-deficient regulatory T cells[J].J Immunol,2017,199(12):3972-3980.
[10]Bocian K,Kiernozek E,Domaga-Kulawik J,et al.Expanding diversity and common goal of regulatory T and B cells.I:origin,phenotype,mechanisms[J].Arch Immunol Ther Exp(Warsz),2017,65(6):501-520.
[11]Banko Z,Pozsgay J,Szili D,et al.Induction and differentiation of IL-10-producing regulatory B cells from healthy blood donors and rheumatoid arthritis patients[J].J Immunol,2017,198(4):1512-1520.
[12]Blair PA,Norena LY,Flores-Borja F,et al.CD19(+)CD24(hi)CD38(hi)B cells exhibit regulatory capacity in healthy individuals but are functionally impaired in systemic Lupus Erythematosus patients[J].Immunity,2010,32(1):129-140.
[13]Ding Q,Yeung M,Camirand G,et al.Regulatory B cells are identified by expression of TIM-1 and can be induced through TIM-1 ligation to promote tolerance in mice[J].J Clin Invest,2011,121(9):3645-3456.
[14]Sarvaria A,Madrigal JA,Saudemont A.B cell regulation in cancer and anti-tumor immunity[J].Cell Mol Immunol,2017,14(8):662-674.
[15]Falcao PL,Tpr C.The role of regulatory T cells,interleukin-10 and in vivo scintigraphy in autoimmune and idiopathic diseases-Therapeutic perspectives and prognosis[J].Rev Assoc Med Bras(1992),2017,63(12):1090-1099.
[16]Houzen H,Kondo K,Niino M,et al.Prevalence and clinical features of neuromyelitis optica spectrum disorders in northern Japan[J].Neurology,2017,89(19):1995-2001.
[17]Zhong H,Liu Y,Xu Z,et al.TGF-β-Induced CD8+CD103+regulatory T cells show potent therapeutic effect on chronic graft-versushost disease lupus by suppressing B cells[J].Front Immunol,2018,9:35.
[18]Song J,Xiao L,Du G,et al.The role of regulatory B cells(Bregs)in the Tregs-amplifying effect of Sirolimus[J].Int Immunopharmacol,2016,38:90-96.
[19]Lucchinetti CF,Guo Y,Popescu BF,et al.The pathology of an autoimmune astrocytopathy:lessons learned from neuromyelitis optica[J].Brain Pathol,2014,24(1):83-97.