HLA检测技术及其应用的研究进展

Review on research progress of detection techniques in human leukocyte antigen and their applications

人类白细胞抗原(HLA)基因检测技术已应用于造血干细胞移植供受者选择、药物个性化治疗、群体遗传多态性和某些疾病关联的研究等方面。近年来国内外HLA研究取得一系列进展包括:升级了《常见及确认的HLA等位基因表》,新一代测序平台应用于HLA基因分型;发现在HLA错配和单体型造血干细胞移植前宜做供者HLA特异性抗体检测;HLA基因与某些药物引发的严重不良反应密切相关,HLA-C区域上游35 kb的1个SNP位点(rs9264942-35C/T)与HLA-C表达水平和个体HIV感染后的病毒载量水平有关;与Hsa-miR-148a结合的HLA-C 3'端非编码区域内的碱基变异可调节HLA-C mRNA的表达。HLA表达沉默的巨核细胞和血小板,可逃避HLA抗体介导的细胞毒性反应,有助于解决血小板输注无效问题。

Human leukocyte antigen （HLA） detection has been selected as a method of choice in hematopoietic stem cell transplantation （HSCT）, personalized drug therapy, population genetic polymorphism study and disease association re- search. Some research progresses were obtained in the HLA field in recent years： common and well-documented HLA alleles were updated, and the newest sequencing technique has been used for HLA genotyping. It was shown that donor HLA-specif- ic antibodies should be detected before mismatches occurred in HSCT for one or more HLA alleles and full HLA haplotype. There was evidence in the association between polymorphisms at HLA loci and severe adverse drug reactions. A single-nucle- otide polymorphism 35 kb upstream of the HLA-C locus （rs9264942-35C/T） showe.d the most significant association with HLA-C expression level and HIV viral load control. Variation within the 3＇ untranslated region of HLA-C with binding of the microRNA hsa-miR-148 can regulate HLA-C mRNA expression level. HLA-silenced megakaryocytes and platelets can escape the complement-dependent cytotoxic effect using specific anti-HLA antibodies, which will help to resolve platelet transfusion refractoriness.