硼替佐米联合化疗对初治多发性骨髓瘤患者DC亚群、IL-6、TNF-α的影响及与β2-MG的相关性研究
发布时间：2018-03-08 15:13
本文选题：多发性骨髓瘤 切入点：树突状细胞 出处：《兰州大学》2016年硕士论文 论文类型：学位论文
【摘要】：目的:探讨初治多发性骨髓瘤(multiple myeloma,MM)患者经硼替佐米联合化疗前后外周血髓样树突状细胞(myeloid dendritic cells,mDC)和浆细胞样树突状细胞(plasmacytoid dendritic cells,pDC)的比例,细胞因子白介素6(interleukin-6,IL-6)、肿瘤坏死因子-α(tumor necrosis factor-alpha,TNF-α)水平的变化及与临床预后指标β2-微球蛋白(β2-microglobulin,β2-MG)的相关性。方法:收集2013年12月~2015年12月在兰州大学第二医院血液科住院部确诊的初治多发性骨髓瘤患者21例,正常对照组11例,患者均使用PAD方案治疗1~2个疗程,应用流式细胞术检测正常对照组、初治MM患者及治疗后mDC与pDC比例,应用酶联免疫吸附试验(enzyme linked immunosorbent assay,ELISA)检测外周血IL-6、TNF-α水平,分析mDC、pDC比例及IL-6、TNF-α水平与β2-MG之间的相关性。结果:1.MM组治疗前与正常对照组相比,mDC比例降低(0.57±0.12%vs1.06±0.10%,P0.001),pDC比例降低(0.17±0.11%vs 0.79±0.10%,P0.001);MM组治疗后与治疗前相比,mDC比例增高(0.98±0.15%vs 0.57±0.12%,P0.001),pDC比例增高(0.69±0.30%vs 0.17±0.11%,P0.001);MM组治疗后与正常对照组相比,mDC比例为(0.98±0.15%vs 1.06±0.10%,P=0.050),pDC比例为(0.69±0.30%vs 0.79±0.10%,P=0.138),差异无统计学意义。比较mDC、pDC比例在不同分期之间的差异,只有Ⅰ期与Ⅲ期之间存在统计学差异:mDC(0.67±0.12%vs 0.52±0.10%,P0.05),pDC(0.28±0.16%vs 0.11±0.04%,P0.05)。2.MM组在治疗前,外周血mDC比例与血清β2-MG水平呈负相关(r=㧟0.569,P0.05),pDC比例与血清β2-MG水平呈负相关(r=㧟0.693,P0.05)。不同分期中,只有Ⅲ期患者外周血mDC比例与血清β2-MG水平呈负相关(r=㧟0.883,P0.05),pDC比例与血清β2-MG水平呈负相关(r=㧟0.881,P0.05)。3.MM组治疗前与正常对照组相比,IL-6水平显著增高(13.78±7.08 vs 4.73±2.19,P0.001),TNF-α水平显著增高(34.05±10.11 vs 14.98±7.57,P0.001),差异有统计学意义。MM组治疗后与治疗前相比,IL-6水平显著降低(6.42±3.33 vs13.78±7.08,P0.001),TNF-α水平显著降低(18.72±5.43 vs 34.05±10.11,P0.001),差异有统计学意义。MM组治疗后与正常对照组相比,IL-6水平为(6.42±3.33 vs 4.73±2.19,P=0.059),TNF-α水平为(18.72±5.43 vs 14.98±7.57,P=0.090),差异无统计学意义。不同分期IL-6、TNF-α的水平也存在统计学差异,Ⅰ期与Ⅱ期相比,IL-6水平显著降低(7.20±3.84 vs 11.78±2.80,P0.05),TNF-α水平显著降低(24.18±5.78 vs 32.92±5.86,P0.05);Ⅰ期与Ⅲ期相比,IL-6水平显著降低(7.20±3.84 vs 19.69±5.97,P0.001),TNF-α水平显著降低(24.18±5.78 vs 41.39±8.87,P0.001);Ⅱ期与Ⅲ期相比,IL-6水平显著降低(11.78±2.80 vs 19.69±5.97,P0.05),TNF-α水平显著降低(32.92±5.86 vs41.39±8.87,P0.05),三组之间均有统计学差异。4.MM组治疗前IL-6水平与血清β2-MG水平呈正相关(r=0.623,P0.01),TNF-α水平与血清β2-MG呈正相关(r=0.769,P0.01),IL-6水平与TNF-α水平呈正相关(r=0.515,P0.05)。不同分期中,只有Ⅲ期患者外周血IL-6水平与血清β2-MG水平呈正相关(r=0.800,P0.05),TNF-α水平与血清β2-MG水平呈正相关(r=0.833,P0.05)。结论:1.初治MM患者治疗前外周血mDC、pDC比例降低,与β2-MG水平呈负相关,初始及继发免疫缺陷可能均参与MM发病;2.初治MM患者治疗前IL-6、TNF-α水平增高,与β2-MG水平呈正相关,提示细胞因子IL-6、TNF-α参与MM发病;3.MM患者分期增加,DC亚群比例降低,细胞因子IL-6、TNF-α水平增高,预后越差;4.硼替佐米治疗可增加DC亚群比例,降低细胞因子IL-6、TNF-α的水平,在一定程度上改善了MM患者免疫紊乱。
[Abstract]:Objective: To investigate the effect of multiple myeloma (multiple myeloma, MM) were treated by bortezomib and bortezomib in combination with chemotherapy on peripheral blood dendritic cells (myeloid dendritic cells, mDC) and plasmacytoid dendritic cells (plasmacytoid dendritic cells, pDC) the ratio of cytokine interleukin 6 (interleukin-6, IL-6), tumor necrosis factor alpha (tumor alpha necrosis factor-alpha, TNF-) level changes and clinical and prognostic indicators of beta 2- microglobulin (beta 2-microglobulin and beta 2-MG) correlation. Methods: from December 2013 ~2015 year in December 21 cases of myeloma patients hospitalized in the Department of Hematology of Second Hospital Affiliated to Lanzhou University of the Ministry confirmed early multiple, 11 in normal control group cases of patients using the PAD regimen in the treatment of 1~2 treatment, the application of flow cytometry in the normal control group, the ratio of mDC and pDC of MM patients with initial treatment and after treatment, using enzyme linked immunosorbent assay (enzyme linked IMM unosorbent assay,ELISA)妫，
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