摘要
目的探讨多发性骨髓瘤(MM)患者骨髓瘤细胞免疫表型CD200的表达和外周血调节性T细胞(Treg)的比例及其在MM预后评估中的意义。方法选择2018年7月至2021年7月于新乡医学院第一附属医院初诊的100例MM患者为研究对象,根据患者骨髓流式细胞术检测结果将患者分为CD200^(+)组(n=77)和CD200^(-)组(n=23)。应用流式细胞术检测骨髓瘤细胞免疫分型、外周血中Treg比例,免疫比浊法测定β_(2)-微球蛋白(β_(2)-MG)水平,乳酸底物法测定乳酸脱氢酶(LDH)水平,肌氨酸氧化酶法测定肌酐(Cr)水平,双缩脲法测定总蛋白(TP)水平,溴甲酚绿法检测白蛋白(ALB),偶氮砷Ⅲ法检测Ca^(2+)水平。比较2组患者骨髓瘤细胞的免疫表型和临床特点,分析CD200、Treg与临床预后的相关性;采用Pearson直线相关性分析Treg的比例与β_(2)-MG、Cr、LDH、Hb的关系;绘制受试者操作特征曲线,并计算曲线下面积以评估Treg对MM预后的预测效能;采用Kaplan-Meier法绘制生存曲线。结果MM患者骨髓瘤细胞的免疫表型CD38、CD138、CD200、CD19、CD56、CD117的阳性率分别为100%(100/100)、100%(100/100)、77%(77/100)、5%(5/100)、68%(68/100)、37%(37/100)。CD200^(+)组患者CD56、CD117的阳性率显著高于CD200^(-)组(P<0.05)。CD200^(+)组患者的Treg、β_(2)-MG、Cr、Ca^(2+)水平均显著高于CD200^(-)组(P<0.05)。Pearson直线相关性分析显示,CD200的表达与CD56、CD117均呈负相关(r=-0.491、-0.222,P<0.05);Treg比例与β_(2)-MG、Cr、LDH均呈正相关(r=0.566、0.373、0.230,P<0.05),与Hb呈负相关(r=-0.209,P<0.05)。CD200^(+)组与CD200^(-)组患者的国际分期系统(ISS)Ⅰ、Ⅱ、Ⅲ期分期比较差异有统计学意义(χ^(2)=8.263,P<0.05),CD200^(+)组患者Ⅲ期病例较多。Treg比例在Ⅰ、Ⅱ、Ⅲ期患者间比较差异有统计学意义(P<0.05)。Treg细胞比例随着ISS分期的升高而增加,Ⅲ期患者中Treg细胞比例最高。ROC曲线结果显示,外周血Treg细胞比例预测MM患者预后的曲线下面积为0.773(95%置信区间为0.681~0.865),以Treg细胞≥6.05%为截断值时,灵敏度为71.1%,特异度为74.5%。100例MM患者中位生存期为25个月。CD200^(-)组患者中位生存期、总生存(OS)率均大于CD200^(+)组(P<0.05),Treg<6.05%的患者中位生存期、OS率均大于Treg≥6.05%患者(P<0.05)。结论骨髓瘤细胞CD200的阳性表达与外周血Treg细胞比例升高是MM患者预后不良的影响因素,对临床评估MM患者预后具有重要意义。
Objective To investigate the expression of immunophenotype CD200 in myeloma cells and the proportion of peripheral blood regulatory T cells(Treg)in patients with multiple myeloma(MM)and their significance in MM prognostic stratification.Methods A total of 100 multiple myeloma(MM)patients admitted to the First Affiliated Hospital of Xinxiang Medical University from July 2018 to July 2021 were enrolled as the research subjects.According to bone marrow flow cytometry results,the patients were divided into CD200^(+)(n=77)group and CD200^(-)(n=23)group.Flow cytometry was used to analyze bone marrow immunophenotyping and Treg proportion in peripheral blood.Serumβ_(2)-microglobulin(β_(2)-MG)was measured by immunoturbidimetry,lactate dehydrogenase(LDH)level was measured by lactate substrate assay,creatinine(Cr)level was measured by sarcosine oxidase method,total protein(TP)was measured by biuret method,albumin(ALB)was measured by bromocresol green assay,and Ca^(2+)was measured by arsenazoⅢmethod.The immunophenotypes and clinical characteristics of myeloma cells of patients were compared between the two groups,and the correlation of CD200 and Treg with clinical prognostic stratification was analyzed.Pearson linear correlation analysis was used to assess the relationship between Treg proportion andβ_(2)-MG,Cr,LDH,and Hb.Receiver operating characteristic(ROC)curve was plotted,and the area under the curve(AUC)was calculated to evaluate the predictive efficacy of Treg for MM prognosis.Kaplan-Meier method was applied to plot survival curves.Results The positive rates of immunophenotypes CD38,CD138,CD200,CD19,CD56,and CD117 in myeloma cells of MM patients were 100%(100/100),100%(100/100),77%(77/100),5%(5/100),68%(68/100),and 37%(37/100),respectively.The positive rates of CD56 and CD117 in the CD200^(+)group were significantly higher than those in the CD200^(-)group(P<0.05).The levels of Treg,β_(2)-MG,Cr,and Ca^(2+)in the CD200^(+)group were significantly higher than those in the CD200^(-)group(P<0.05).Pearson linear correlation analysis showed that CD200 expression was negatively correlated with CD56 and CD117(r=-0.497,-0.222;P<0.05),Treg proportion was positively correlated withβ_(2)-MG,Cr,and LDH(r=0.566,0.373,0.230;P<0.05),and negatively correlated with Hb(r=-0.209,P<0.05).There were statistically significant differences in the international staging system(ISS)stagesⅠ,Ⅱ,andⅢof patients between CD200^(+)group and CD200^(-)group(χ^(2)=8.263,P<0.05).Patients in the CD200^(+)group had a higher proportion of stageⅢcases.Additionally,there were significant differences in the proportion of Treg among patients in stagesⅠ,Ⅱ,andⅢ(F=11.67,P<0.05),and the proportion of Treg increased as the ISS stage advanced.ROC curve analysis showed that AUC of peripheral blood Treg proportion for predicting MM prognosis was 0.773(95%confidence interval:0.681-0.865).With a cutoff value of Treg≥6.05%,the sensitivity was 71.1%,and the specificity was 74.5%.The median survival time of 100 MM patients was 25 months.The median survival time and overall survival(OS)rate in the CD200^(-)group were longer/higher than those in the CD200^(+)group(P<0.05),and patients with Treg<6.05%had a longer median survival time and higher OS rate than those with Treg≥6.05%(P<0.05).Conclusion The positive expression of CD200 in myeloma cells and the increased proportion of peripheral blood Treg proportion are important factors contributing to poor prognosis in MM patients,which hold significant clinical significance for evaluating the prognosis of MM patients.
作者
宋琛
尹明梅
孙亚洲
戴许阳
张晨光
SONG Chen;YIN Mingmei;SUN Yazhou;DAI Xuyang;ZHANG Chenguang(Hematology Laboratory of the First Affiliated Hospital of Xinxiang Medical University,Weihui 453100,Henan Province,China;Xinxiang Key Laboratory of Precision Diagnosis of Experimental Hematology,Weihui 453100,Henan Province,China;Department of Respiratory Intensive Care Unit,the First Affiliated Hospital of Xinxiang Medical University,Weihui 453100,Henan Province,China;Department of Pediatrics,the First Affiliated Hospital of Xinxiang Medical University,Weihui 453100,Henan Province,China;School of Public Health,Xinxiang Medical University,Xinxiang 453003,Henan Province,China)
出处
《新乡医学院学报》
2025年第8期631-636,共6页
Journal of Xinxiang Medical University
基金
河南省医学科技攻关计划联合共建项目(编号:LHGJ20210518
LHGJ20240459)。
