摘要
目的探讨1例红细胞抗高频抗原抗体并阐明其血型遗传机制。方法选取2016年8月由衢州市中医院送检至浙江省血液中心的1例Lan-个体作为研究对象。采用回顾性研究方法,收集该个体的临床资料,用试管盐水法和微柱凝集抗人球法鉴定其红细胞抗原及血清意外抗体,用7种酶处理和2种化学还原剂处理红细胞,鉴定其血清抗体的特异性。提取该个体的基因组DNA,进行全基因组测序(WGS)、红细胞血型基因分析,并用Sanger测序法进行验证。应用多种生物信息学软件对变异位点的有害性进行分析,并根据血型血清学和血型基因的检测结果,综合判断该个体的稀有血型及其意外抗体的特异性。本研究通过了浙江省血液中心医学伦理委员会的审查(批准号:20190201)。结果该个体为男性,91岁,汉族,患有前列腺及膀胱炎,营养不良、消瘦。曾接受多次红细胞输血,均无明显的反应。最近1次输血前交叉配血出现主侧凝集,送本实验室进行抗体鉴定。先证者血清中检出抗高频抗原抗体,酶法和还原剂法排除MNS、LU、KEL等17种血型系统的抗体特异性。WGS分析得到红细胞血型基因4525个SNP和1046个INDEL变异,进一步筛选分析发现先证者为rs755723161纯合变异导致的稀有血型。该变异为ATP结合转运蛋白B超家族成员6(ABCB6)基因c.459delC变异导致多肽链p.Trp154GlyfsTer96改变,形成红细胞高频抗原缺失的Lan-稀有血型,并在血清中产生IgG抗Lan。结论该研究发现了Lan-患者产生的抗Lan同种抗体,并首次阐明了中国人ABCB6基因变异所致Lan-稀有血型。
Objective To investigate a case of antibodies against high-frequency erythrocyte antigens and elucidate the genetic mechanism underlying the blood group.Methods A Lan-negative patient referred to the Zhejiang Blood Center by Quzhou Hospital of Traditional Chinese Medicine in August 2016 was selected as the study subject.A retrospective study was conducted to collect the proband's clinical data.The proband's erythrocyte antigens and unexpected serum antibodies were identified using tube saline and microcolumn agglutination anti-human globulin methods.Antibody specificity was determined by treating erythrocytes with 7 enzymes and 2 chemical reducing agents.Genomic DNA was extracted from the proband's blood sample for whole genome sequencing(WGS)and erythrocyte blood group gene analysis,with validation by Sanger sequencing.Multiple bioinformatics tools were used to analyze the pathogenicity of the variant.The rare blood group and unexpected antibody specificity were comprehensively determined based on the results of serological and genetic testing.This study has been approved by the Zhejiang Provincial Blood Center Medical Ethics Committee(Ethics No.20190201).Results The proband was a 91-year-old Han Chinese male with prostatitis,cystitis,and malnutrition in conjunct with emaciation.He had a history of multiple erythrocyte transfusions without observable adverse reactions.Prior to the most recent transfusion,major crossmatch agglutination was observed,which prompted antibody identification.Antibodies against high-frequency antigens were detected in the proband's serum,with enzyme and reducing agent treatments ruling out antibody specificities associated with 17 blood group systems,e.g.,MNS,LU,KEL.WGS analysis identified 4525 SNPs and 1046 INDEL variants among erythrocyte blood group genes.Further screening revealed that the proband had a rare blood group due to a homozygous rs755723161 variant.This variant in the ABCB6 gene(c.459delC)has led to a frameshifting mutation(p.Trpl54GlyfsTer96),resulting in the Lan-negative rare blood group with a high-frequency antigen deficiency and the production of IgG anti-Lan antibodies in the serum.Conclusion This study has identified anti-Lan alloantibodies in a Lan-negative patient and,for the first time,elucidated the ABCB6 gene variant underlying the Lan-negative rare blood group in the Chinese population.
作者
许先国
马开荣
刘瑛
洪小珍
应燕玲
朱发明
Xu Xianguo;Ma Kairong;Liu Ying;Hong Xiaozhen;Ying Yanling;Zhu Faming(Blood Center of Zhejiang Province,Hangzhou,Zhejiang 310052,China)
出处
《中华医学遗传学杂志》
2025年第3期286-291,共6页
Chinese Journal of Medical Genetics
基金
中国输血协会威高科研基金重点项目(CSBT-MWG-2023-01)。
