HLA-DRB1等位基因和抗HLA-DRB1抗体在尿毒症患者中的分布特征

Distribution Characteristics of the HLA-DRB1 Allele and Anti-HLADRB1Antibodies in Uremia Patients

为了研究华南地区尿毒症患者的HLA-DRB1等位基因频率分布及抗HLA-DRB1抗体类型,收集尿毒症患者和健康对照者的外周血,通过聚合酶链反应-序列特异性寡核苷酸探针(PCR-SSO)方法对HLA-DRB1等位基因进行基因分型。经Luminex系统检测因尿毒症进行肾移植的患者中抗HLA-DRB1抗体的类型和频率,用HLAMatchmaker数据库比较和分析HLA-DRB1的表位及其氨基酸序列,通过统计软件分析患者中HLA等位基因和抗HLA抗体的类型和频率。结果发现:与健康对照者相比,尿毒症患者HLA-DRB1*13等位基因的频率显著低于健康对照者(4.33%vs.13.37%,P<0.001);HLA-DRB1*14等位基因的频率显著高于健康对照者(12.01%vs.4.12%,P<0.001)。在所有类型的抗HLA-DRB1抗体中,抗HLA-DRB1*01/*13/*14抗体的频率显著低于其他抗HLA-DRB1抗体的频率(P<0.05)。经HLAMatchmaker数据库分析发现,HLA-DRB1*01/*13/*14等位基因中的常见表位为77T。这表明:在基因频率上,HLA-DRB1*13与尿毒症患病率呈负相关,可能对个体具有保护作用;HLADRB1*14与尿毒症患病率呈正相关,可能是尿毒症的易感因素。尿毒症患者中抗HLA-DRB1*01/*13/*14抗体的水平显著低于其他抗HLA-DRB1抗体,这可能是由存在的共同表位77T所致。研究结果将为深入了解HLA-DRB1基因与尿毒症的关系奠定基础,对阐明HLA-DRB1基因在尿毒症及肾移植中的作用提供试验依据。

In order to study the frequency distribution of HLA-DRB1 alleles and anti-HLA-DRB1 antibody types in patients with uremia in southern China,the peripheral blood of uremia patients and healthy controls(HCs)was collected,and HLADRB1 allele was genotyped via polymerase chain reaction-sequence specific oligonucleotide probes(PCR-SSO).A Luminex system was used to detect the types and frequencies of anti-HLA-DRB1 antibodies in patients undergoing renal transplantation due to uremia.HLAMatchmaker database was used to compare and analyze the epitopes of HLA-DRB1 and their amino-acid sequences.The types and frequencies of HLA alleles and anti-HLA antibodies in patients were analyzed by statistical software.It was found that the frequency of the HLA-DRB1*13 allele in uremia patients was significantly lower than that of HCs(4.33%vs. 13.37%, P<0.001), the frequency of the HLA-DRB1*14 allele was significantly higher than that of HCs (12.01% vs. 4.12%,P<0.001). Among all types of anti-HLA-DRB1 antibodies, the frequency of anti-HLA-DRB1*01/*13/*14 antibodies was significantlylower than that of other anti-HLA-DRB1 antibodies (P<0.05). A common epitope 77T in HLA-DRB1*01/*13/*14alleles was discovered using HLAMatchmaker database. These indicate that in terms of gene frequency, HLA-DRB1*13 is correlatednegatively with uremia prevalence and may have protective effects on individuals. HLA-DRB1*14 is correlated positivelywith uremia prevalence, and may be a susceptible factor of uremia. Levels of anti-HLA-DRB1*01/ *13/*14 antibodies in uremiapatients were significantly lower than those of other anti-HLA-DRB1 antibodies, probably due to the presence of a commonepitope 77T. This study will lay the foundation for an in-depth understanding of the relationship between HLA-DRB1 gene anduremia, and provide experimental evidence for elucidating the role of HLA-DRB1 gene in uremia and kidney transplantation.