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
Gilbert综合征(Gilbert syndrome,GS)是因尿苷二磷酸葡萄糖醛酸转移酶1家族成员A1(UDPglucuronosyltransferase family 1 member A1,UGT1A1)基因突变导致尿苷二磷酸葡萄糖醛酸转移酶(uridine diphosphate glucuronosyltransferase,UGT酶...Gilbert综合征(Gilbert syndrome,GS)是因尿苷二磷酸葡萄糖醛酸转移酶1家族成员A1(UDPglucuronosyltransferase family 1 member A1,UGT1A1)基因突变导致尿苷二磷酸葡萄糖醛酸转移酶(uridine diphosphate glucuronosyltransferase,UGT酶)活性降低、以慢性非结合性高胆红素血症为特征的遗传性疾病,患者典型临床表现为间歇性黄疸,转氨酶正常,确诊依赖UGT1A1基因检测[1-2]。遗传性球形红细胞增多症(hereditary spherocytosis,HS)是红细胞膜蛋白基因突变导致红细胞球形化并在脾脏破坏增加,进而引发的溶血性疾病,患者典型表现为贫血、黄疸和脾大,可有外周血球形红细胞增多、渗透脆性增加,基因检测可明确ANK1、SPTA1等突变[3]。两病共患时可因临床表现重叠发生误诊或漏诊。现对我单位收治的1例GS共患HS行腹腔镜下脾切除的患者诊治经过总结报道如下。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Gilbert综合征(Gilbert syndrome,GS)是因尿苷二磷酸葡萄糖醛酸转移酶1家族成员A1(UDPglucuronosyltransferase family 1 member A1,UGT1A1)基因突变导致尿苷二磷酸葡萄糖醛酸转移酶(uridine diphosphate glucuronosyltransferase,UGT酶)活性降低、以慢性非结合性高胆红素血症为特征的遗传性疾病,患者典型临床表现为间歇性黄疸,转氨酶正常,确诊依赖UGT1A1基因检测[1-2]。遗传性球形红细胞增多症(hereditary spherocytosis,HS)是红细胞膜蛋白基因突变导致红细胞球形化并在脾脏破坏增加,进而引发的溶血性疾病,患者典型表现为贫血、黄疸和脾大,可有外周血球形红细胞增多、渗透脆性增加,基因检测可明确ANK1、SPTA1等突变[3]。两病共患时可因临床表现重叠发生误诊或漏诊。现对我单位收治的1例GS共患HS行腹腔镜下脾切除的患者诊治经过总结报道如下。
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。
