Background:In patients with autoimmune hemolytic anemia(AIHA),the risk of relapse is high owing to persistent autoreactive B-cell activity.Multirefractory AIHA is a more advanced stage of disease that is defined by a ...Background:In patients with autoimmune hemolytic anemia(AIHA),the risk of relapse is high owing to persistent autoreactive B-cell activity.Multirefractory AIHA is a more advanced stage of disease that is defined by a lack of response to at least three lines of therapy.CD19-directed chimeric antigen receptor(CAR)T-cell therapy results in profound B-cell depletion and may be a useful approach to achieving drug-free remission in multirefractory AIHA.展开更多
The occurrence of severe thalassemia,an inherited blood disorder that is either blood-transfusiondependent or fatal,can be mitigated through carrier screening.Here,we aim to evaluate the effectiveness and outcomes of ...The occurrence of severe thalassemia,an inherited blood disorder that is either blood-transfusiondependent or fatal,can be mitigated through carrier screening.Here,we aim to evaluate the effectiveness and outcomes of pre-conceptional and early pregnancy screening initiatives for severe thalassemia prevention in a diverse population of 28,043 women.Using next-generation sequencing(NGS),we identify 4,226(15.07%)thalassemia carriers across 29 ethnic groups and categorize them into high-(0.75%),low-(25.86%),and unknown-risk(69.19%)groups based on their spouses'screening results.Post-screening follow-up reveals 59 fetuses with severe thalassemia exclusively in high-risk couples,underscoring the efficacy of risk classification.Among 25,053 live births over 6 months of age,two severe thalassemia infants were born to unknown-risk couples,which was attributed to incomplete screening and late NGS-based testing for a rare variant.Notably,64 rare variants are identified in 287 individuals,highlighting the genetic heterogeneity of thalassemia.We also observe that migrant flow significantly impacts carrier rates,with 93.90%of migrants to Chenzhou originating from high-prevalence regions in southern China.Our study demonstrates that NGS-based screening during pre-conception and early pregnancy is effective for severe thalassemia prevention,emphasizing the need for continuous screening efforts in areas with high and underestimated prevalence.展开更多
目的探讨血常规红细胞参数在地中海贫血(地贫)初步筛查中的应用价值,建立基于红细胞参数的筛查模型。方法选取2023年1月—2024年6月本院地贫疑似患者200例(地贫组120例,非地贫组80例),采集静脉血行血常规检测[获取平均红细胞体积(mean c...目的探讨血常规红细胞参数在地中海贫血(地贫)初步筛查中的应用价值,建立基于红细胞参数的筛查模型。方法选取2023年1月—2024年6月本院地贫疑似患者200例(地贫组120例,非地贫组80例),采集静脉血行血常规检测[获取平均红细胞体积(mean corpuscular volume,MCV)、平均红细胞血红蛋白含量(mean corpuscular hemoglobin,MCH)、红细胞分布宽度变异系数(red cell distribution width-coefficient of variation,RDW-CV)等参数]及地贫基因检测(金标准)。比较两组红细胞参数差异,通过受试者工作特征(receiver operating characteristic,ROC)曲线分析参数筛查效能,构建联合筛查模型。结果地贫组MCV[(72.3±5.8)fL vs(89.5±4.2)fL]、MCH[(24.1±3.5)pg vs(30.2±2.8)pg]显著低于非地贫组(P<0.001);RDW-CV两组无统计学差异(P=0.12>0.05)。MCV筛查地贫的曲线下面积(area under the curve,AUC)为0.91[95%置信区间(confidence interval,CI):0.87~0.95],截断值≤76 fL时敏感性93.3%、特异性88.8%;MCV联合MCH筛查的AUC提升,敏感性95.0%、特异性92.5%。结论血常规红细胞参数可作为地贫高效、经济的初步筛查指标,联合检测可进一步提高筛查效能,适用于基层医疗机构推广。展开更多
文摘Background:In patients with autoimmune hemolytic anemia(AIHA),the risk of relapse is high owing to persistent autoreactive B-cell activity.Multirefractory AIHA is a more advanced stage of disease that is defined by a lack of response to at least three lines of therapy.CD19-directed chimeric antigen receptor(CAR)T-cell therapy results in profound B-cell depletion and may be a useful approach to achieving drug-free remission in multirefractory AIHA.
基金supported by the National Natural Science Foundation of China(81760037)Yunling Scholar Project of Yunnan Province(YNWR-YLXZ-2019-0005)+1 种基金Hunan Provincial Innovation Platform and Talent Program(2018SK4004)Hunan Provincial Natural Science Foundation(2019JJ80048).
文摘The occurrence of severe thalassemia,an inherited blood disorder that is either blood-transfusiondependent or fatal,can be mitigated through carrier screening.Here,we aim to evaluate the effectiveness and outcomes of pre-conceptional and early pregnancy screening initiatives for severe thalassemia prevention in a diverse population of 28,043 women.Using next-generation sequencing(NGS),we identify 4,226(15.07%)thalassemia carriers across 29 ethnic groups and categorize them into high-(0.75%),low-(25.86%),and unknown-risk(69.19%)groups based on their spouses'screening results.Post-screening follow-up reveals 59 fetuses with severe thalassemia exclusively in high-risk couples,underscoring the efficacy of risk classification.Among 25,053 live births over 6 months of age,two severe thalassemia infants were born to unknown-risk couples,which was attributed to incomplete screening and late NGS-based testing for a rare variant.Notably,64 rare variants are identified in 287 individuals,highlighting the genetic heterogeneity of thalassemia.We also observe that migrant flow significantly impacts carrier rates,with 93.90%of migrants to Chenzhou originating from high-prevalence regions in southern China.Our study demonstrates that NGS-based screening during pre-conception and early pregnancy is effective for severe thalassemia prevention,emphasizing the need for continuous screening efforts in areas with high and underestimated prevalence.
文摘温抗体型自身免疫性溶血性贫血(warm autoimmune hemolytic anemia,wAIHA)是由自身抗体介导的自身免疫性疾病。随着对wAIHA免疫发病机制的深入理解,针对免疫系统不同靶点的药物研发取得了显著进展,为wAIHA患者的治疗提供了更多选择。以新型CD20单抗、Bruton酪氨酸激酶(Bruton tyrosine kinase,BTK)抑制剂、磷脂酰肌醇3激酶(phosphatidylinositol 3-kinases,PI3K)抑制剂和B淋巴细胞活化因子(B-cell activating factor of the TNF family,BAFF)抑制剂等为代表的抗B细胞靶向治疗,以及以蛋白酶体抑制剂和CD38单抗为代表的抗浆细胞靶向治疗均取得了显著成效。此外,补体抑制剂、新生儿Fc受体(neonatal Fc receptor,FcRn)单抗、脾酪氨酸激酶(spleen tyrosine kinase,SYK)抑制剂、哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)抑制剂等也取得了显著进展。本文对近年来wAIHA的免疫靶向治疗进展进行综述,以期为临床实践提供参考。
文摘目的探讨血常规红细胞参数在地中海贫血(地贫)初步筛查中的应用价值,建立基于红细胞参数的筛查模型。方法选取2023年1月—2024年6月本院地贫疑似患者200例(地贫组120例,非地贫组80例),采集静脉血行血常规检测[获取平均红细胞体积(mean corpuscular volume,MCV)、平均红细胞血红蛋白含量(mean corpuscular hemoglobin,MCH)、红细胞分布宽度变异系数(red cell distribution width-coefficient of variation,RDW-CV)等参数]及地贫基因检测(金标准)。比较两组红细胞参数差异,通过受试者工作特征(receiver operating characteristic,ROC)曲线分析参数筛查效能,构建联合筛查模型。结果地贫组MCV[(72.3±5.8)fL vs(89.5±4.2)fL]、MCH[(24.1±3.5)pg vs(30.2±2.8)pg]显著低于非地贫组(P<0.001);RDW-CV两组无统计学差异(P=0.12>0.05)。MCV筛查地贫的曲线下面积(area under the curve,AUC)为0.91[95%置信区间(confidence interval,CI):0.87~0.95],截断值≤76 fL时敏感性93.3%、特异性88.8%;MCV联合MCH筛查的AUC提升,敏感性95.0%、特异性92.5%。结论血常规红细胞参数可作为地贫高效、经济的初步筛查指标,联合检测可进一步提高筛查效能,适用于基层医疗机构推广。
