重型再生障碍性贫血免疫发病机制的研究
摘要
研究目的：
为探讨重型再生障碍性贫血(SAA)患者T细胞激活及免疫耐受打破的机制，特进行以下研究：
1．测定重型再生障碍性贫血(SAA)患者在免疫抑制治疗(IST)前后外周血树突状细胞亚群数量、比值的变化。
2．测定SAA患者外周血T细胞激活协同分子(CD80、CD86、CD40)在DC及B细胞表面的表达。
3．测定SAA患者外周血Th3细胞、CD4~+CD25~+调节T细胞数量和血浆中调节因子TGF-β1水平。
4 了解肝炎相关再生障碍性贫血(HAAA)在重型再生障碍性贫血(SAA)中所占比例并探讨其临床特征。
5．探讨慢性乙型肝炎病毒(HBV)感染并发重型再生障碍性贫血(SAA)的临床特征。
研究方法：
1．用单克隆抗体三标法，以流式细胞仪检测26例发病期和13例IST后恢复的SAA患者外周血pDC1与pDC2的数量、比例，并与15名正常对照组比较。其中10例患者检测了治疗前和治疗后2个月的pDC1与pDC2的数量。
2．用单克隆抗体双标法，以流式细胞仪检测16例SAA患者及12名正常对照外周血DC及B淋巴细胞CD80、CD86、CD40的表达。
Purpose:
To probe the mechanisms of T cell activation and distolerance of immunity in severe aplastic anemia. We have done the studies as follows:
1. Detecting the quantity, ratio of monocyte-derived dendritic cell precursors (pDC1) and plasmacytoid dendritic cell precursors (pDC2) in peripheral blood mononuclear cell (PBMC) of severe aplastic anemia(SAA)patients before and after immune suppressive therapy (IST).
2. Detecting the expression of T-cell co-stimulating molecules (CD80, CD86, CD40) on DC and B cells surface in the SAA patients' peripheral blood.
3. Measuring the percentage of Th3 cells and CD4+ CD25+ T regulator cells in peripheral blood and detecting the levels of TGF-β1 in serum of patients with SAA at disease active and recovery phases and that of normal controls.
4. To explore the ratio of hepatitis associated aplastic anemia (HAAA) to severe aplastic anemia (SAA) and its clinical features.
5. To explore the clinical features of severe aplastic anemia (SAA) patients with chronic hepatitis B virus (HBV) infection.
为探讨重型再生障碍性贫血(SAA)患者T细胞激活及免疫耐受打破的机制，特进行以下研究：
1．测定重型再生障碍性贫血(SAA)患者在免疫抑制治疗(IST)前后外周血树突状细胞亚群数量、比值的变化。
2．测定SAA患者外周血T细胞激活协同分子(CD80、CD86、CD40)在DC及B细胞表面的表达。
3．测定SAA患者外周血Th3细胞、CD4~+CD25~+调节T细胞数量和血浆中调节因子TGF-β1水平。
4 了解肝炎相关再生障碍性贫血(HAAA)在重型再生障碍性贫血(SAA)中所占比例并探讨其临床特征。
5．探讨慢性乙型肝炎病毒(HBV)感染并发重型再生障碍性贫血(SAA)的临床特征。
研究方法：
1．用单克隆抗体三标法，以流式细胞仪检测26例发病期和13例IST后恢复的SAA患者外周血pDC1与pDC2的数量、比例，并与15名正常对照组比较。其中10例患者检测了治疗前和治疗后2个月的pDC1与pDC2的数量。
2．用单克隆抗体双标法，以流式细胞仪检测16例SAA患者及12名正常对照外周血DC及B淋巴细胞CD80、CD86、CD40的表达。
Purpose:
To probe the mechanisms of T cell activation and distolerance of immunity in severe aplastic anemia. We have done the studies as follows:
1. Detecting the quantity, ratio of monocyte-derived dendritic cell precursors (pDC1) and plasmacytoid dendritic cell precursors (pDC2) in peripheral blood mononuclear cell (PBMC) of severe aplastic anemia(SAA)patients before and after immune suppressive therapy (IST).
2. Detecting the expression of T-cell co-stimulating molecules (CD80, CD86, CD40) on DC and B cells surface in the SAA patients' peripheral blood.
3. Measuring the percentage of Th3 cells and CD4+ CD25+ T regulator cells in peripheral blood and detecting the levels of TGF-β1 in serum of patients with SAA at disease active and recovery phases and that of normal controls.
4. To explore the ratio of hepatitis associated aplastic anemia (HAAA) to severe aplastic anemia (SAA) and its clinical features.
5. To explore the clinical features of severe aplastic anemia (SAA) patients with chronic hepatitis B virus (HBV) infection.
引文
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5. Melenhorst JJ, van Krieken JHJM,Dreef E, et al. T cells selectively infiltrate bone marrow areas with residual haemopoiesis of patients with acquired aplastic anaemia.Br J Haematol, 1997,99:517-519.
6. Laver J, Castro-Malaspina H, Kernan NA, et al. In vitro interferon-gamma production by cultured T-cells in severe aplastic anaemia: correlation with granulomonopoietic inhibition in patients who respond to antithymocyte globulin. Br J Haematol, 1988,69:545-550
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8．陈慰峰，主编．医学免疫学．第四版．北京：人民卫生出版社，2004，152-153．
9. Kook H, Zeng W, Gubin C, et al. Increased cytotoxic T cells with effector phenotype in aplastic anemia and myelodysplasia. Exp Hematol ,2001,29 : 1270-1277.
10．和虹，邵宗鸿，何广胜，等．Thl细胞在再生障碍性贫血发病机制中的作用．中华血液学杂志，2002，23：574-577．
11. Sloand E , Kim S , Maciejewski JP , et al Intracellular interferon-gamma in circulating and marrow T cells detected by flow cytometry and the response to immunosuppressive therapy in patients with aplastic anemia.Blood, 2002,100:1185-1191.
12．何广胜，邵宗鸿，和虹，等．重型再生障碍性贫血患者骨髓中辅助性T细胞亚群数量及功能的变化．中华血液学杂志，2004，25：613-616．
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3. Laver J, Castro-Malaspina H, Kernan NA, et al. In vitro interferon-gamma production by cultured T-cells in severe aplastic anaemia: correlation with granulomonopoietic inhibition in patients who respond to antithymocyte globulin. Br J Haematol, 1988, 69:545-550
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5．陈慰峰，主编．医学免疫学．第四版．北京：人民卫生出版社，2004，102-103．
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31. Kook H, Zeng W, Gubin C, et al. Increased cytotoxic T cells with??effector phenotype in aplastic anemia and myelodysplasia. Exp Hematol ,2001,29 : 1270-1277.
32．和虹，邵宗鸿，何广胜，等．Th1细胞在再生障碍性贫血发病机制中的作用．中华血液学杂志，2002，23：574-577．
33. Sloand E , Kim S , Maciejewski JP , et al . Intracellular interferon-gamma in circulating and marrow T cells detected by flow cytometry and the response to immunosuppressive therapy in patients with aplastic anemia.Blood, 2002,100 : 1185-1191.
34．何广胜，邵宗鸿，和虹，等．重型再生障碍性贫血患者骨髓中辅助性T细胞亚群数量及功能的变化．中华血液学杂志，2004，25：613-616．
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