目的探讨(1-3)-β-D葡聚糖联合降钙素原(procalcitonin,PCT)、CD4^(+)T淋巴细胞多指标在艾滋病患者马尔尼菲篮状菌感染早期诊断临床研究。方法回顾性选取我院2020年1月—2022年6月住院的120例艾滋病患者为研究对象。依据实验室结果,将...目的探讨(1-3)-β-D葡聚糖联合降钙素原(procalcitonin,PCT)、CD4^(+)T淋巴细胞多指标在艾滋病患者马尔尼菲篮状菌感染早期诊断临床研究。方法回顾性选取我院2020年1月—2022年6月住院的120例艾滋病患者为研究对象。依据实验室结果,将其分为马尔尼菲篮状菌感染确诊组(血或组织液培育养出马尔尼菲篮状菌),简称A组(62例),及马尔尼菲篮状菌感染临床诊断组[根据临床症状、体征、血常规及(1-3)-β-D葡聚糖、PCT、CD4^(+)T淋巴细胞多指标诊断],简称B组(58例)。检测患者(1-3)-β-D葡聚糖、PCT、CD4^(+)T淋巴细胞的表达水平,采用受试者工作特征(receiver-operating characteristic,ROC)曲线下面积(area under the curve,AUC)评估上述指标联合检测对艾滋病患者感染马尔尼菲篮状菌的诊断效能。结果A组的(1-3)-β-D葡聚糖和PCT水平均高于B组,CD4^(+)T淋巴细胞个数低于B组(P<0.05);(1-3)-β-D葡聚糖、PCT、CD4^(+)T淋巴细胞联合检测的AUC为0.933,(1-3)-β-D葡聚糖单独检测的AUC是0.812,PCT单独检测的AUC为0.883,CD4^(+)T淋巴细胞单独检测的AUC是0.810,(1-3)-β-D葡聚糖、PCT和CD4^(+)T淋巴细胞联合检测的AUC皆优于三项单独检测,表明(1-3)-β-D葡聚糖、PCT和CD4^(+)T淋巴细胞联合检测的诊断价值皆优于单一指标诊断,且联合检测的特异度、约登指数分别为92.43%和0.580,均高于三项单独检测。结论(1-3)-β-D葡聚糖联合PCT和CD4^(+)T淋巴细胞多指标对艾滋病马尔尼菲篮状菌感染具有非常高的临床诊断价值,能够帮助医生分析出高危风险患者,及时制定治疗方案,同时也承担预后效果的判断依据,对治疗艾滋病马尔尼菲篮状菌感染具有非常重要的研究价值。展开更多
目的:以往研究表明4-1BB和GITR均可表达于CD4+CD25+调节T细胞(regulatory T cell,Tr),在由该细胞群维持的自身耐受中起着重要作用。另有研究报道人外周血CD4+CD25highT细胞与该Tr的功能活性更为接近,且在多发性硬化(multiple sclerosis,...目的:以往研究表明4-1BB和GITR均可表达于CD4+CD25+调节T细胞(regulatory T cell,Tr),在由该细胞群维持的自身耐受中起着重要作用。另有研究报道人外周血CD4+CD25highT细胞与该Tr的功能活性更为接近,且在多发性硬化(multiple sclerosis,MS)患者中的效应功能明显降低,但目前对其是否与上述两类分子的表达有关尚不清楚,因此我们检测了MS患者外周血CD4+CD25highT细胞上4-1BB、GITR的表达,旨在发现该调节T细胞群是否有上述分子的异常表达。方法:用流式细胞仪检测了未治疗MS、其他神经系统疾病患者、正常对照组外周血CD4+CD25highT细胞表面4-1BB、GITR的表达。结果:与正常对照比较,MS患者CD4+CD25highT细胞4-1BB的表达明显减少(P<0.05),而在CD4+CD25-T细胞的表达则与正常对照无明显差别(P>0.05)。三组间CD4+CD25highT细胞及其GITR的表达亦无显著差别(P>0.05)。结论:本研究发现MS患者CD4+CD25highT细胞上4-1BB的表达减少,而GITR的表达则较正常对照组则无显著差别,我们的结果提示该细胞群免疫活性的降低可能与其4-1BB的表达下调有关,而GITR则在CD4+CD25highT细胞的免疫调节过程中可能发挥着次要或精细调节的作用。展开更多
Objective:Previous studies reported that 4-1BB-based CD19 chimeric antigen receptor(CAR)-T cells were more beneficial for the clinical outcomes than CD28-based CAR-T cells,especially the lower incidence rate of severe...Objective:Previous studies reported that 4-1BB-based CD19 chimeric antigen receptor(CAR)-T cells were more beneficial for the clinical outcomes than CD28-based CAR-T cells,especially the lower incidence rate of severe adverse events.However,the median progression-free survival(mPFS)of 4-1BB-based product Kymriah was shorter than that of CD28-based Yescarta(2.9 months vs.5.9 months),suggesting that Kymriah was limited in the long-term efficacy.Thus,a safe and durable 4-1BB-based CD19 CAR-T needs to be developed.Methods:We designed a CD19-targeted CAR-T(named as IM19)which consisted of an FMC63 scFv,4-1BB and CD3ζintracellular domain and was manufactured into a memory T-enriched formulation.A phase I/II clinical trial was launched to evaluate the clinical outcomes of IM19 in relapsed or refractory(r/r)B cell non-Hodgkin lymphoma(B-NHL).Dose-escalation investigation(at a dose of 5×10^(5)/kg,1×10^(6)/kg and 3×106/kg)was performed in 22 r/r B-NHL patients.All patients received a single infusion of IM19 after 3-day conditional regimen.Results:At month 3,the overall response rate(ORR)was 59.1%,the complete response rate(CRR)was 50.0%.The mPFS was 6 months and the 1-year overall survival rate was 77.8%.Cytokine release syndrome(CRS)occurred in 13 patients(59.1%),with 54.5%of grade 1−2 CRS.Only one patient(4.5%)experienced grade 3 CRS and grade 3 neurotoxicity.Conclusions:These results demonstrated the safety and durable efficacy of a 4-1BB-based CD19 CAR-T,IM19,which is promising for further development and clinical investigation.展开更多
文摘目的探讨(1-3)-β-D葡聚糖联合降钙素原(procalcitonin,PCT)、CD4^(+)T淋巴细胞多指标在艾滋病患者马尔尼菲篮状菌感染早期诊断临床研究。方法回顾性选取我院2020年1月—2022年6月住院的120例艾滋病患者为研究对象。依据实验室结果,将其分为马尔尼菲篮状菌感染确诊组(血或组织液培育养出马尔尼菲篮状菌),简称A组(62例),及马尔尼菲篮状菌感染临床诊断组[根据临床症状、体征、血常规及(1-3)-β-D葡聚糖、PCT、CD4^(+)T淋巴细胞多指标诊断],简称B组(58例)。检测患者(1-3)-β-D葡聚糖、PCT、CD4^(+)T淋巴细胞的表达水平,采用受试者工作特征(receiver-operating characteristic,ROC)曲线下面积(area under the curve,AUC)评估上述指标联合检测对艾滋病患者感染马尔尼菲篮状菌的诊断效能。结果A组的(1-3)-β-D葡聚糖和PCT水平均高于B组,CD4^(+)T淋巴细胞个数低于B组(P<0.05);(1-3)-β-D葡聚糖、PCT、CD4^(+)T淋巴细胞联合检测的AUC为0.933,(1-3)-β-D葡聚糖单独检测的AUC是0.812,PCT单独检测的AUC为0.883,CD4^(+)T淋巴细胞单独检测的AUC是0.810,(1-3)-β-D葡聚糖、PCT和CD4^(+)T淋巴细胞联合检测的AUC皆优于三项单独检测,表明(1-3)-β-D葡聚糖、PCT和CD4^(+)T淋巴细胞联合检测的诊断价值皆优于单一指标诊断,且联合检测的特异度、约登指数分别为92.43%和0.580,均高于三项单独检测。结论(1-3)-β-D葡聚糖联合PCT和CD4^(+)T淋巴细胞多指标对艾滋病马尔尼菲篮状菌感染具有非常高的临床诊断价值,能够帮助医生分析出高危风险患者,及时制定治疗方案,同时也承担预后效果的判断依据,对治疗艾滋病马尔尼菲篮状菌感染具有非常重要的研究价值。
文摘目的:以往研究表明4-1BB和GITR均可表达于CD4+CD25+调节T细胞(regulatory T cell,Tr),在由该细胞群维持的自身耐受中起着重要作用。另有研究报道人外周血CD4+CD25highT细胞与该Tr的功能活性更为接近,且在多发性硬化(multiple sclerosis,MS)患者中的效应功能明显降低,但目前对其是否与上述两类分子的表达有关尚不清楚,因此我们检测了MS患者外周血CD4+CD25highT细胞上4-1BB、GITR的表达,旨在发现该调节T细胞群是否有上述分子的异常表达。方法:用流式细胞仪检测了未治疗MS、其他神经系统疾病患者、正常对照组外周血CD4+CD25highT细胞表面4-1BB、GITR的表达。结果:与正常对照比较,MS患者CD4+CD25highT细胞4-1BB的表达明显减少(P<0.05),而在CD4+CD25-T细胞的表达则与正常对照无明显差别(P>0.05)。三组间CD4+CD25highT细胞及其GITR的表达亦无显著差别(P>0.05)。结论:本研究发现MS患者CD4+CD25highT细胞上4-1BB的表达减少,而GITR的表达则较正常对照组则无显著差别,我们的结果提示该细胞群免疫活性的降低可能与其4-1BB的表达下调有关,而GITR则在CD4+CD25highT细胞的免疫调节过程中可能发挥着次要或精细调节的作用。
基金supported by the Beijing Natural Science Foundation (No. 7202026)Capital’s Funds for Health Improvement and Research (No. 2020-2Z-2157)
文摘Objective:Previous studies reported that 4-1BB-based CD19 chimeric antigen receptor(CAR)-T cells were more beneficial for the clinical outcomes than CD28-based CAR-T cells,especially the lower incidence rate of severe adverse events.However,the median progression-free survival(mPFS)of 4-1BB-based product Kymriah was shorter than that of CD28-based Yescarta(2.9 months vs.5.9 months),suggesting that Kymriah was limited in the long-term efficacy.Thus,a safe and durable 4-1BB-based CD19 CAR-T needs to be developed.Methods:We designed a CD19-targeted CAR-T(named as IM19)which consisted of an FMC63 scFv,4-1BB and CD3ζintracellular domain and was manufactured into a memory T-enriched formulation.A phase I/II clinical trial was launched to evaluate the clinical outcomes of IM19 in relapsed or refractory(r/r)B cell non-Hodgkin lymphoma(B-NHL).Dose-escalation investigation(at a dose of 5×10^(5)/kg,1×10^(6)/kg and 3×106/kg)was performed in 22 r/r B-NHL patients.All patients received a single infusion of IM19 after 3-day conditional regimen.Results:At month 3,the overall response rate(ORR)was 59.1%,the complete response rate(CRR)was 50.0%.The mPFS was 6 months and the 1-year overall survival rate was 77.8%.Cytokine release syndrome(CRS)occurred in 13 patients(59.1%),with 54.5%of grade 1−2 CRS.Only one patient(4.5%)experienced grade 3 CRS and grade 3 neurotoxicity.Conclusions:These results demonstrated the safety and durable efficacy of a 4-1BB-based CD19 CAR-T,IM19,which is promising for further development and clinical investigation.
