rhG-CSF动员对健康供者外周血淋巴细胞亚群和免疫功能的影响
|
摘要
目的探讨重组人粒细胞集落刺激因子(rhG-CSF)动员对健康供者外周血淋巴细胞亚群和免疫功能状态的影响。方法 2017年1月—2018年3月在广州军区广州总医院血液科进行外周血造血干细胞动员及采集的健康供者57例,使用rhG-CSF 5～10μg/(kg·d)连续5 d皮下注射进行外周血造血干细胞动员,于动员第0、3、5天采集供者外周血,使用流式细胞术检测淋巴细胞亚群,使用全自动生化仪检测免疫功能五项。结果动员第0、3、5天供者外周血中,总淋巴细胞百分比下降,动员第5天下降尤为明显(P<0.05)。总T细胞(CD3~+)、辅助/诱导T淋巴细胞(CD3~+CD4~+)、总B淋巴细胞(CD19~+)亚群比例在动员第3天上升,第5天降低,但差异无统计学意义(均P>0.05)。抑制/细胞毒T淋巴细胞(CD3~+CD8~+)、NK细胞(CD3~-CD56~+)细胞亚群在动员后呈下降趋势,但差异无统计学意义(均P>0.05)。CD4~+/CD8~+比值有上升趋势,但差异无统计学意义(P>0.05)。动员第0、3、5天供者外周血中免疫球蛋白(IgA、IgG、IgM)和补体(C3、C4)水平无明显变化(均P>0.05)。结论 rhG-CSF动员不影响健康供者外周血淋巴细胞亚群和免疫功能,能安全应用于造血干细胞动员。
Objective To investigate the effects of recombinant human granulocyte colony-stimulating factor(rhG-CSF) mobilization therapy on lymphocyte subsets and immune function in peripheral blood of the normal stem cell donors.Methods Hematopoietic stem cell mobilization and collection were performed on 57 normal stem cell donors in the Department of Hematology, General Hospital of Guangzhou Military Command from January 2017 to March 2018. RhG-CSF(5-10 μg·kg~(-1)·d~(-1)) was administered subcutaneously for 5 days to mobilize hematopoietic stem cells(HSCs). Peripheral blood from donors was collected on the 0 th, 3 rd, and 5 th day after the mobilization therapy. Then lymphocyte subsets were detected by using flow cytometry. Immunoglobulins and complements were detected by using automatic biochemical analyzer. Results In the peripheral blood of donors on day 0, 3, and 5 after mobilization therapy, the percentage of total lymphocytes decreased, and the decrease was particularly significant on the 5 th day of mobilization(P<0.05). The proportion of total T cells(CD3~+), T helper cells(CD3~+CD4~+), and B lymphocytes(CD19~+) increased on the 3 rd day of mobilization and decreased on the 5 th day, but the difference was not statistically significant(P>0.05). The subpopulations of cytotoxic T lymphocytes(CD3~+CD8~+) and NK cells(CD3~-CD56~+) showed a downward trend after mobilization, but the difference was not statistically significant(P>0.05). The CD4~+/CD8~+ ratio showed an upward trend, but without statistically significance(P>0.05). There were no significant changes in the levels of immunoglobulins(IgA, IgG, IgM) and complements(C3, C4) in the peripheral blood of the donors on days 0, 3 and 5 of mobilization(P>0.05). Conclusion The rhG-CSF mobilization therapy does not affect lymphocyte subsets and immune function in the peripheral blood of normal stem cell donors, which can be safely applied to hematopoietic stem cell mobilization.
Objective To investigate the effects of recombinant human granulocyte colony-stimulating factor(rhG-CSF) mobilization therapy on lymphocyte subsets and immune function in peripheral blood of the normal stem cell donors.Methods Hematopoietic stem cell mobilization and collection were performed on 57 normal stem cell donors in the Department of Hematology, General Hospital of Guangzhou Military Command from January 2017 to March 2018. RhG-CSF(5-10 μg·kg~(-1)·d~(-1)) was administered subcutaneously for 5 days to mobilize hematopoietic stem cells(HSCs). Peripheral blood from donors was collected on the 0 th, 3 rd, and 5 th day after the mobilization therapy. Then lymphocyte subsets were detected by using flow cytometry. Immunoglobulins and complements were detected by using automatic biochemical analyzer. Results In the peripheral blood of donors on day 0, 3, and 5 after mobilization therapy, the percentage of total lymphocytes decreased, and the decrease was particularly significant on the 5 th day of mobilization(P<0.05). The proportion of total T cells(CD3~+), T helper cells(CD3~+CD4~+), and B lymphocytes(CD19~+) increased on the 3 rd day of mobilization and decreased on the 5 th day, but the difference was not statistically significant(P>0.05). The subpopulations of cytotoxic T lymphocytes(CD3~+CD8~+) and NK cells(CD3~-CD56~+) showed a downward trend after mobilization, but the difference was not statistically significant(P>0.05). The CD4~+/CD8~+ ratio showed an upward trend, but without statistically significance(P>0.05). There were no significant changes in the levels of immunoglobulins(IgA, IgG, IgM) and complements(C3, C4) in the peripheral blood of the donors on days 0, 3 and 5 of mobilization(P>0.05). Conclusion The rhG-CSF mobilization therapy does not affect lymphocyte subsets and immune function in the peripheral blood of normal stem cell donors, which can be safely applied to hematopoietic stem cell mobilization.
引文
[1] LEE C J,SAVANI B N,MOHTY M,et al.Post-remission strategies for the prevention of relapse following allogeneic hematopoietic cell transplantation for high-risk acute myeloid leukemia:expert review from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation[J].Bone Marrow Transplant,2018.doi:10.1038/s41409-018-0286-2.
[2] TYNDALL A.Hematopoietic stem cell transplantation for autoimmune diseases:more than just prolonged immunosuppression[J].Curr Opin Hematol,2018,25(6):433-440.
[3] TAY J,LEVESQUE J P,WINKLER I G.Cellular players of hematopoietic stem cell mobilization in the bone marrow niche[J].Int J Hematol,2017,105(2):129-140.
[4] GYURKOCZA B,LAZARUS H M,GIRALT S.Allogeneic hematopoietic cell transplantation in patients with AML not achieving remission:potentially curative therapy[J].Bone Marrow Transplant,2017,52(8):1083-1090.
[5] IKEDA K,OHTO H,OKUYAMA Y,et al.Adverse events qssociated with infusion of hematopoietic stem cell products:a prospective and multicenter surveillance study[J].Transfus Med Rev,2018,39(5):382.
[6] 袁乐欣,李桃,江苇妍,等.广东省大学生对外周血造血干细胞捐献安全性认知现状及影响因素[J].广东医学,2016,37(6):898-901.
[7] REZVANI A R,STORER B E,GUTHRIE K A,et al.Impact of donor age on outcome after allogeneic hematopoietic cell transplantation[J].Biol Blood Marrow Transplant,2015,21(1):105-112.
[8] 中国红十字会.中国造血干细胞捐献者资料库(中华骨髓库).统计信息[EB/OL][2018-09-30].http://www.cmdp.org.cn/.
[9] 丁娜妮,焦阳,高晟,等.温州市居民非亲缘外周血造血干细胞捐献意愿的影响因素[J].温州医科大学学报,2018,48(1):72-75.
[10] 苏力,闫超,郑磊,等.影响造血干细胞志愿捐献者捐献决定的心理因素初步研究[J].中国心理卫生杂志,2016,30(11):806-811.
[11] 郭翔,惠飞,张博,等.非亲缘造血干细胞捐献者的心理焦虑原因分析与应对[J].中国输血杂志,2015,28(9):1165-1167.
[12] FLOMMERSFELD S,SOHLBACH K,JAQUES G,et al.Collection of peripheral blood progenitor cells on Day 4 is feasible and effective while reducing granulocyte-colony-stimulating factor exposure to healthy donors[J].Transfusion,2015,55(6):1269-1274.
[13] 林文诗,施京京,胡佳丽.浙江省公众造血干细胞捐献意识的调查与分析[J].医学与哲学(A),2015,36(10):56-57,77.
[14] IWASAKI A,MEDZHITOV R.Control of adaptive immunity by the innate immune system[J].Nat Immunol,2015,16(4):343-353.
[15] MCCOY K D,RONCHI F,GEUKING M B.Host-microbiota interactions and adaptive immunity[J].Immunol Rev,2017,279(1):63-69.
[16] WHERRY E J,KURACHI M.Molecular and cellular insights into T cell exhaustion[J].Nat Rev Immunol,2015,15(8):486-499.
[17] CHAMBERS A M,LUPO K B,MATOSEVIC S.Tumor microenvironment-induced immunometabolic reprogramming of natural killer cells[J].Front Immunol,2018,9:2517.
[18] HALE M,RAWLINGS D J,JACKSON S W.The long and the short of it:insights into the cellular source of autoantibodies as revealed by B cell depletion therapy[J].Curr Opin Immunol,2018,55:81-88.
[19] DEAL C E,BALAZS A B.Engineering humoral immunity as prophylaxis or therapy[J].Curr Opin Immunol,2015,35:113-122.
[20] EKDAHL K N,PERSSON B MOHLIN C,et al.Interpretation of serological complement biomarkers in disease[J].Front Immunol,2018,9:2237.
[2] TYNDALL A.Hematopoietic stem cell transplantation for autoimmune diseases:more than just prolonged immunosuppression[J].Curr Opin Hematol,2018,25(6):433-440.
[3] TAY J,LEVESQUE J P,WINKLER I G.Cellular players of hematopoietic stem cell mobilization in the bone marrow niche[J].Int J Hematol,2017,105(2):129-140.
[4] GYURKOCZA B,LAZARUS H M,GIRALT S.Allogeneic hematopoietic cell transplantation in patients with AML not achieving remission:potentially curative therapy[J].Bone Marrow Transplant,2017,52(8):1083-1090.
[5] IKEDA K,OHTO H,OKUYAMA Y,et al.Adverse events qssociated with infusion of hematopoietic stem cell products:a prospective and multicenter surveillance study[J].Transfus Med Rev,2018,39(5):382.
[6] 袁乐欣,李桃,江苇妍,等.广东省大学生对外周血造血干细胞捐献安全性认知现状及影响因素[J].广东医学,2016,37(6):898-901.
[7] REZVANI A R,STORER B E,GUTHRIE K A,et al.Impact of donor age on outcome after allogeneic hematopoietic cell transplantation[J].Biol Blood Marrow Transplant,2015,21(1):105-112.
[8] 中国红十字会.中国造血干细胞捐献者资料库(中华骨髓库).统计信息[EB/OL][2018-09-30].http://www.cmdp.org.cn/.
[9] 丁娜妮,焦阳,高晟,等.温州市居民非亲缘外周血造血干细胞捐献意愿的影响因素[J].温州医科大学学报,2018,48(1):72-75.
[10] 苏力,闫超,郑磊,等.影响造血干细胞志愿捐献者捐献决定的心理因素初步研究[J].中国心理卫生杂志,2016,30(11):806-811.
[11] 郭翔,惠飞,张博,等.非亲缘造血干细胞捐献者的心理焦虑原因分析与应对[J].中国输血杂志,2015,28(9):1165-1167.
[12] FLOMMERSFELD S,SOHLBACH K,JAQUES G,et al.Collection of peripheral blood progenitor cells on Day 4 is feasible and effective while reducing granulocyte-colony-stimulating factor exposure to healthy donors[J].Transfusion,2015,55(6):1269-1274.
[13] 林文诗,施京京,胡佳丽.浙江省公众造血干细胞捐献意识的调查与分析[J].医学与哲学(A),2015,36(10):56-57,77.
[14] IWASAKI A,MEDZHITOV R.Control of adaptive immunity by the innate immune system[J].Nat Immunol,2015,16(4):343-353.
[15] MCCOY K D,RONCHI F,GEUKING M B.Host-microbiota interactions and adaptive immunity[J].Immunol Rev,2017,279(1):63-69.
[16] WHERRY E J,KURACHI M.Molecular and cellular insights into T cell exhaustion[J].Nat Rev Immunol,2015,15(8):486-499.
[17] CHAMBERS A M,LUPO K B,MATOSEVIC S.Tumor microenvironment-induced immunometabolic reprogramming of natural killer cells[J].Front Immunol,2018,9:2517.
[18] HALE M,RAWLINGS D J,JACKSON S W.The long and the short of it:insights into the cellular source of autoantibodies as revealed by B cell depletion therapy[J].Curr Opin Immunol,2018,55:81-88.
[19] DEAL C E,BALAZS A B.Engineering humoral immunity as prophylaxis or therapy[J].Curr Opin Immunol,2015,35:113-122.
[20] EKDAHL K N,PERSSON B MOHLIN C,et al.Interpretation of serological complement biomarkers in disease[J].Front Immunol,2018,9:2237.