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应用 HLAMatchmaker 检测多胎妊娠等待心脏移植患者的抗 HLA-A、-B、-DR、-DQB1 和 -DQA1 抗体反应性表位。

Anti-HLA-A, -B, -DR, -DQB1 and -DQA1 antibodies reactive epitope determination with HLAMatchmaker in multipare awaiting list for heart transplant.

机构信息

U.O.C. Immunohematology, Transfusion Medicine and Transplant Immunology (SIMT), Regional Reference Laboratory of Transplant Immunology (LIT), Azienda Universitaria Policlinico (AOU), Second University of Naples, Italy.

出版信息

Hum Immunol. 2013 Aug;74(8):937-41. doi: 10.1016/j.humimm.2013.04.033. Epub 2013 Apr 27.

DOI:10.1016/j.humimm.2013.04.033
PMID:23628396
Abstract

Human leukocyte antigen (HLA) antibodies represent a significant risk factor for transplant failure. It is very important to characterize anti-HLA antibodies as epitopes rather than antigens so that this knowledge can be applied clinically. The aim of the study was to investigate the extra reactivity patterns in sensitized multipare. Here, we have used the HLAMatchmaker program, a theoretical algorithm, to explain these unexpected antibody reactivity patterns in multipare awaiting for heart transplant. The patient was sensitized during pregnancy by alleles HLA-A()24:02, HLA-DRB1()07:01, HLA-DRB4()01:01, DQB1()02:02 and DQA1()02:01 mismatches with development of respective antibodies. However, the patient' sera were shown an unexpected reactivity not directed toward HLA mismatches of daughters: A(∗)23:01, A()24:03 and B()15:12 for class I and DRB4()01:03, DRB1()09:02, DRB1()09:01, DQB1()03:01, DQB1()03:03, DQB1()03:02, DQB1()04:02, DQB1()04:01 and DQB1()02:01 for class II. By HLAMatchmaker analysis we found that these antibodies reacted with eplet shared by antigens in single allele Luminex panels. These eplets were: 62EE, 66GKH, 70KAH, 71HS, 127K, 113YH, 144KR, 150AAH, 151AHV, 163TG and 167DG for class I and 4Q, 74RRAE, 71RRA, 98KN, 120N, and 135G, 25FT, 34HE, 41ER, 47EK2, 48LF for class II. Thus, HLAMatchmaker software together with to solid phase techniques could open new horizons for a more precise characterization of the HLA-antibodies.

摘要

人类白细胞抗原 (HLA) 抗体是移植失败的一个重要危险因素。将抗 HLA 抗体描述为表位而不是抗原非常重要,以便将这些知识应用于临床。本研究的目的是研究致敏多胎妊娠中的额外反应模式。在这里,我们使用了 HLAMatchmaker 程序,这是一种理论算法,来解释多胎妊娠中等待心脏移植的患者中这些意外的抗体反应模式。该患者在怀孕期间因 HLA-A()24:02、HLA-DRB1()07:01、HLA-DRB4()01:01、DQB1()02:02 和 DQA1()02:01 等位基因不匹配而致敏,并发展出相应的抗体。然而,患者的血清显示出针对女儿 HLA 不匹配的意外反应:A(∗)23:01、A()24:03 和 B()15:12 为 I 类,DRB4()01:03、DRB1()09:02、DRB1()09:01、DQB1()03:01、DQB1()03:03、DQB1()03:02、DQB1()04:02、DQB1()04:01 和 DQB1()02:01 为 II 类。通过 HLAMatchmaker 分析,我们发现这些抗体与单等位基因 Luminex 面板中抗原的共享 eplet 反应。这些 eplet 是:I 类的 62EE、66GKH、70KAH、71HS、127K、113YH、144KR、150AAH、151AHV、163TG 和 167DG,以及 II 类的 4Q、74RRAE、71RRA、98KN、120N 和 135G、25FT、34HE、41ER、47EK2、48LF。因此,HLAMatchmaker 软件与固相技术相结合,可以为更精确地描述 HLA 抗体开辟新的视野。

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