本文選題：血細(xì)胞減少 + 免疫相關(guān)　； 參考：《天津醫(yī)科大學(xué)》2009年碩士論文

【摘要】： 目的:了解免疫相關(guān)性全血細(xì)胞減少(immuno-related pancytopenia,IRP)患者骨髓液補(bǔ)體水平的變化及調(diào)節(jié)性T細(xì)胞(regulatory T cells)數(shù)量和功能狀況,探討補(bǔ)體在IRP患者骨髓造血細(xì)胞破壞機(jī)制中的作用以及調(diào)節(jié)性T細(xì)胞在IRP免疫發(fā)病機(jī)制中的作用。 方法:研究對(duì)象為124例IRP患者,其中初治患者(初治組)59例、經(jīng)激素免疫抑制及促造血治療后血象恢復(fù)正常患者(恢復(fù)組)65例及正常對(duì)照24名。采用ELISA法測(cè)定其骨髓上清中的補(bǔ)體膜攻擊復(fù)合物(C5b-9)、補(bǔ)體總?cè)苎钚?CH50)、補(bǔ)體C3、C4水平及調(diào)節(jié)性T細(xì)胞相關(guān)的細(xì)胞因子白細(xì)胞介素(interleukin,IL)-2、TGF-β的水平,并使用流式細(xì)胞術(shù)(FCM)檢測(cè)IRP患者骨髓單個(gè)核細(xì)胞膜抗體(CD34~+細(xì)胞、Glyco-A~+細(xì)胞、CD15~+細(xì)胞膜表面自身抗體IgG、IgM)的結(jié)合率及調(diào)節(jié)性T細(xì)胞數(shù)量(CD4~+CD25~+/CD4~+細(xì)胞)、調(diào)節(jié)性T細(xì)胞激活狀態(tài)(CD4~+CD25~+CD127~-/CD4~+細(xì)胞);RT-PCR方法檢測(cè)其骨髓單個(gè)核細(xì)胞調(diào)節(jié)性T細(xì)胞轉(zhuǎn)錄因子FoxP3和Galectin-10的mRNA表達(dá)。 結(jié)果: 1.IRP初治組患者骨髓C5b-9水平(119.82±53.95)明顯高于恢復(fù)組(100.74±33.42)和正常對(duì)照組(93.86±28.81)(p均＜0.05),而恢復(fù)組患者骨髓C5b-9與正常對(duì)照組比較差異無統(tǒng)計(jì)學(xué)意義(p＞0.05);IRP初治組、恢復(fù)組患者骨髓CH50水平(33.29±11.51,30.77±10.34)高于正常對(duì)照組(24.09±6.37)(p＜0.05),初治組高于恢復(fù)組,但差異無統(tǒng)計(jì)學(xué)意義(p＞0.05);IRP初治組、恢復(fù)組患者骨髓補(bǔ)體C3水平(4.90±2.19,4.95±3.47)明顯低于正常對(duì)照組(6.98±5.56)(p＜0.05),初治組患者骨髓補(bǔ)體C3與恢復(fù)組比較差異無統(tǒng)計(jì)學(xué)意義(p＞0.05);補(bǔ)體C4水平在IRP各組間比較差異無統(tǒng)計(jì)學(xué)意義(p值均＞0.05);血清補(bǔ)體水平檢測(cè)結(jié)果與骨髓上清中結(jié)果一致。骨髓C5b-9與CH50水平呈顯著正相關(guān)(r=0.241,p=0.003),骨髓CH50與C3水平呈顯著負(fù)相關(guān)(r=-0.303,p=0.007)。IRP患者初治組與恢復(fù)組骨髓造血細(xì)胞膜抗體IgG型占55.17%,IgM型占54.31%,IgG+IgM型占31.90%,含IgM陽性占86.21%。IRP患者IgM陽性組與IgM陰性組C5b-9水平比較,IgM陽性組高于IgM陰性組(p＜0.05)。骨髓補(bǔ)體C5b-9水平與CD34~+-IgG陽性率、CD34~+-IgM陽性率均呈顯著正相關(guān)。(r=0.593,p=0.000;r=0.326,p=0.049)。骨髓補(bǔ)體CH50水平與網(wǎng)織紅細(xì)胞比例呈顯著正相關(guān)(r=0.421,p=0.000),與間接膽紅素呈顯著正相關(guān)(r=0.230,p=0.032),與血紅蛋白、白細(xì)胞、血小板、骨髓紅系比例均無相關(guān)(p均＞0.05)。我們觀察了8例IRP患者激素、免疫抑制治療前后各指標(biāo)的變化,網(wǎng)織紅細(xì)胞(reticulocytic Ret)治療后降至正常(p=0.038),WBC治療后升高至正常(p=0.002),骨髓補(bǔ)體C3水平治療后升高(p=0.003),治療后CD34~+-IgG、CD34~+-IgM陽性率均降低(p=0.016、p=0.022)。 2.IRP初治組、恢復(fù)組患者骨髓IL-2水平(5.64±1.70,6.19±2.53)顯著低于正常對(duì)照組(7.91±3.71)(p＜0.05),初治組低于恢復(fù)組,但差異無統(tǒng)計(jì)學(xué)意義(p＞0.05);IRP初治組、恢復(fù)組患者骨髓TGF-β水平(1.79±0.67,1.86±0.77)顯著低于正常對(duì)照組(2.48±0.94)(p＜0.05),初治組低于恢復(fù)組,但差異無統(tǒng)計(jì)學(xué)意義(p＞0.05);IRP初治組患者骨髓中CD4~+CD25~+/CD4~+細(xì)胞數(shù)量(22.46±9.47)明顯減低,低于正常對(duì)照組(30.59±8.58)(p均＜0.05),而恢復(fù)組與正常對(duì)照組比較差異無統(tǒng)計(jì)學(xué)意義(p＞0.05);IRP初治組患者骨髓CD4~+CD25~+CD127~-/CD4~+細(xì)胞數(shù)量(7.18±2.72)明顯低于正常對(duì)照組(10.44±3.24)(p＜0.05),而恢復(fù)組與正常對(duì)照組比較差異無統(tǒng)計(jì)學(xué)意義(p＞0.05);初治組、恢復(fù)組、正常對(duì)照組三組FoxP3 mRNA的相對(duì)表達(dá)量分別為(0.34±0.25)、(0.69±0.51)和(0.82±0.65),初治組明顯低于恢復(fù)組和正常對(duì)照組(p均＜0.05),初治組、恢復(fù)組、正常對(duì)照組Galectin-10 mRNA的相對(duì)表達(dá)量分別為(0.66±0.11)、(0.74±0.11)和(0.76±0.09),初治組明顯低于恢復(fù)組和正常對(duì)照組(p均＜0.05)。 結(jié)論:IRP患者特別是自身抗體為IgM者其外周血細(xì)胞減少與骨髓單個(gè)核細(xì)胞自身抗體激活補(bǔ)體破壞造血細(xì)胞有關(guān);調(diào)節(jié)性T細(xì)胞的數(shù)量和功能異常在IRP免疫發(fā)病機(jī)制中發(fā)揮重要作用。
[Abstract]:Objective: To investigate the changes in the complement level of bone marrow fluid in patients with Immuno-related pancytopenia (IRP) and the number and function of regulatory T cells (regulatory T cells), and to explore the use of complement in the destruction mechanism of bone marrow hematopoietic cells in IRP patients and the role of regulatory T cells in the pathogenesis of IRP. Use.
Methods: the subjects were 124 patients with IRP, of which 59 cases were first treated (initial treatment group), 65 cases and 24 normal controls were restored to normal patients after hormone immunosuppression and hematopoiesis. The complement membrane attack complex (C5b-9), total complement hemolytic activity (CH50), complement C3, C4 level were measured by ELISA method. Regulatory T cell related cytokines interleukin (IL) -2, TGF- beta level, and the use of flow cytometry (FCM) to detect the membrane antibody of bone marrow mononuclear cells in IRP patients (CD34~+ cells, Glyco-A~+ cells, CD15~+ cell membrane surface autoantibody IgG, IgM) and regulating cell number The activated state of the ganglion T cells (CD4~+CD25~+CD127~-/CD4~+ cells), and the RT-PCR method to detect the mRNA expression of the regulatory T cell transcription factor FoxP3 and Galectin-10 in the mononuclear cells of the bone marrow.
Result:
The bone marrow C5b-9 level of the 1.IRP group (119.82 + 53.95) was significantly higher than that in the recovery group (100.74 + 33.42) and the normal control group (93.86 + 28.81) (P < 0.05), while the bone marrow C5b-9 in the recovery group was not significantly different from that of the normal control group (P > 0.05), and the level of the bone marrow CH50 in the recovery group was higher than that of the recovery group (33.29 + 11.51,30.77 + 10.34). In the normal control group (24.09 + 6.37) (P < 0.05), the initial treatment group was higher than the recovery group, but the difference was not statistically significant (P > 0.05). The level of bone marrow complement C3 (4.90 + 2.19,4.95 3.47) in the recovery group was significantly lower than that of the normal control group (6.98 + 5.56) (P < 0.05). There was no significant difference between the bone marrow complement C3 and the recovery group in the primary treatment group (P > P >). 0.05): there was no significant difference in the level of complement C4 between the groups of IRP (P > 0.05); the results of serum complement level were consistent with the results of bone marrow supernatant. There was a significant positive correlation between bone marrow C5b-9 and CH50 level (r=0.241, p=0.003), and a significant negative correlation between the bone marrow CH50 and C3 level (r=-0.303, p=0.007) and the bone marrow of the primary and recovery groups of the.IRP patients. The hematopoietic cell membrane antibody IgG type accounted for 55.17%, the IgM type accounted for 54.31%, the IgG+IgM type accounted for 31.90%, the IgM positive group was compared with the C5b-9 level in the IgM positive group and the IgM negative group, and the IgM positive group was higher than the IgM negative group (P < 0.05). 26, p=0.049). The level of bone marrow complement CH50 was positively correlated with the ratio of reticulocyte (r=0.421, p=0.000). There was a significant positive correlation with indirect bilirubin (r=0.230, p=0.032). There was no correlation with hemoglobin, leukocyte, platelets, and bone marrow erythroid ratio (P > 0.05). We observed 8 cases of IRP patients hormone, and all indexes before and after immunosuppressive therapy. After treatment, the reticulocyte (reticulocytic Ret) was reduced to normal (p=0.038) after treatment. After WBC treatment, it increased to normal (p=0.002), and after C3 level of bone marrow complement increased (p=0.003). The positive rate of CD34~+-IgG and CD34~+-IgM decreased (p=0.016, p=0.022) after treatment.
2.IRP in the primary treatment group (5.64 + 1.70,6.19 + 2.53) in the recovery group was significantly lower than that in the normal control group (7.91 + 3.71) (P < 0.05), and the initial treatment group was lower than the recovery group, but the difference was not statistically significant (P > 0.05). The level of TGF- beta in the recovery group was significantly lower than that of the normal control group (1.79 + 0.67,1.86 + 0.77) (2.48 + 0.94) (P < 0.05) (P < 0.05). The initial treatment group was lower than the recovery group, but the difference was not statistically significant (P > 0.05). The number of CD4~+CD25~+/CD4~+ cells in the bone marrow (22.46 + 9.47) in the initial IRP group was significantly lower than that in the normal control group (30.59 + 8.58) (P < 0.05), but there was no significant difference between the recovery group and the normal control group (P > 0.05), and the bone marrow CD4~+CD25 in the primary treatment group of IRP was CD4~+CD25. The number of ~+CD127~-/CD4~+ cells (7.18 + 2.72) was significantly lower than that in the normal control group (10.44 + 3.24) (P < 0.05), but there was no significant difference between the recovery group and the normal control group (P > 0.05). The relative expression of FoxP3 mRNA in the early treatment group, the recovery group and the normal control group was (0.34 + 0.25), (0.69 + 0.51) and (0.82 + 0.65), and the primary treatment group was significantly lower. In the recovery group and the normal control group (P < 0.05), the relative expression of Galectin-10 mRNA in the primary treatment group, the recovery group and the normal control group was (0.66 + 0.11), (0.74 + 0.11) and (0.76 + 0.09), and the primary treatment group was significantly lower than the recovery group and the normal control group (P < 0.05).
Conclusion: the decrease of peripheral blood cells in patients with IRP, especially autoantibodies of IgM, is related to the destruction of hematopoietic cells by autoantibody activating complement of bone marrow mononuclear cells, and the number and dysfunction of regulatory T cells play an important role in the mechanism of IRP immunization.

【學(xué)位授予單位】：天津醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2009
【分類號(hào)】：R392

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10 張\，

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