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妊娠同种免疫中的母体 HLA Ib 多态性。

Maternal HLA Ib Polymorphisms in Pregnancy Allo-Immunization.

机构信息

Centre for Immune Regulation and Reproductive Immunology (CIRRI), Department of Clinical Biochemistry, The ReproHealth Research Consortium ZUH, Zealand University Hospital, Roskilde, Denmark.

Aix Marseille Univ, CNRS, EFS, ADES, "Biologie des Groupes Sanguins", Marseille, France.

出版信息

Front Immunol. 2021 Mar 30;12:657217. doi: 10.3389/fimmu.2021.657217. eCollection 2021.

Abstract

During pregnancy the formation of alloreactive anti-human leukocyte antigen (HLA) antibodies are a major cause of acute rejection in organ transplantation and of adverse effects in blood transfusion. The purpose of the study was to identify maternal HLA class Ib genetic factors associated with anti-HLA allo-immunization in pregnancy and the degree of tolerance estimated by IgG4 expression. In total, 86 primiparous women with singleton pregnancies were included in the study. Maternal blood samples and umbilical cord samples were collected at delivery. Clinical data were obtained. Maternal blood serum was screened for HLA class I and II antibodies, identification of Donor Specific Antibody (DSA), activation of complement measured by C1q and IgG4 concentrations. Mothers were genotyped for HLA class Ib ( and ). Anti-HLA class I and II antibodies were identified in 24% of the women. The maternal allele was significantly associated with a higher fraction of anti-HLA I immunization (20.0% 4.8%, p = 0.048). The maternal HLA-G 3'-untranslated region haplotype and the allele were significantly associated with a low anti-HLA I C1q activation (16.7% . 57.1%, p = 0.028; 16.7% 50.0%, p = 0.046; respectively). Both and - showed significantly higher levels of IgG4 compared with the other haplotypes. The results support an association of certain alleles with allo-immunization during pregnancy. Further studies are needed to elucidate the roles of and in reducing the risk for allo-immunization.

摘要

在怀孕期间,同种异体抗人类白细胞抗原 (HLA) 抗体的形成是器官移植中急性排斥反应和输血不良反应的主要原因。本研究旨在鉴定与妊娠期间 HLA 同种免疫相关的母体 HLA Ib 遗传因素,以及通过 IgG4 表达估计的耐受程度。共纳入 86 例初产妇单胎妊娠。分娩时采集母血和脐血样本。获得临床数据。母血清筛查 HLA I 和 II 类抗体,鉴定供体特异性抗体 (DSA),通过 C1q 和 IgG4 浓度测量补体激活。对母亲 HLA Ib(和)进行基因分型。24%的女性识别出抗 HLA I 和 II 抗体。母性等位基因与较高比例的抗 HLA I 免疫(20.0% 4.8%,p = 0.048)显著相关。母体 HLA-G 3'-非翻译区单倍型和等位基因与低抗 HLA I C1q 激活显著相关(16.7%. 57.1%,p = 0.028;16.7% 50.0%,p = 0.046;分别)。与其他单倍型相比,和-显示出显著更高水平的 IgG4。研究结果支持某些等位基因与妊娠期间同种免疫相关。需要进一步研究阐明和在降低同种免疫风险中的作用。

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