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表达 HLA-DQβ1*0202 等位基因的急性肾移植排斥反应受者体液抗体发作减少。

Decreased humoral antibody episodes of acute renal allograft rejection in recipients expressing the HLA-DQβ1*0202 allele.

机构信息

Department of Pathology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA.

出版信息

Exp Mol Pathol. 2012 Oct;93(2):190-2. doi: 10.1016/j.yexmp.2012.05.005. Epub 2012 May 17.

Abstract

The present investigation was designed to show the effect of human leukocyte antigen (HLA) class II molecular allelic specificities in the recipient on the induction of humoral antibody rejection, identified by C4d peritubular capillary staining, as well as specific antibody identified by Luminex technology. Major histocompatibility complex (MHC) class II molecules are expressed on dendritic cells, macrophages, and B lymphocytes and they present antigenic peptides to CD4 positive T lymphocytes. Human renal peritubular and glomerular capillaries express class II MHC molecules upon activation. Expression of class II molecules on renal microvascular endothelial cells exposes them to possible interaction with specific circulating antibodies. We hypothesize that HLA-DQβ10202 expression in recipients decreases the likelihood of antibody-mediated renal allograft rejection. We found that 80% (=25) of DQ2 positive haplotype recipients failed to induce humoral antibody renal allograft rejection and 20% (n=25) of DQ2 positive haplotype recipients induced humoral antibody renal allograft rejection (p=0.008). By contrast, 48% (n=46) of DQ2 negative haplotype recipients failed to induce a humoral antibody component of renal allograft rejection and 52% (n=46) of DQ2 negative haplotype recipients induced humoral antibody-mediated renal allograft rejection. Our results suggest that recipients who express the DQβ10202 allele are less likely to induce a humoral antibody component of acute renal allograft rejection than are those expressing DQ1, DQ3, or DQ4 alleles. DQβ1*0202 allele expression in recipients could possibly be protective against acute humoral allograft rejection and might serve as a future criterion in recipient selection and in appropriate therapy for acute renal rejection episodes.

摘要

本研究旨在探讨受者人类白细胞抗原(HLA)II 类分子等位基因特异性对体液抗体排斥反应的诱导作用,通过 C4d 管周毛细血管染色和 Luminex 技术鉴定的特异性抗体进行鉴定。主要组织相容性复合体(MHC)II 类分子在树突状细胞、巨噬细胞和 B 淋巴细胞上表达,并将抗原肽呈递给 CD4 阳性 T 淋巴细胞。人类肾小管周和肾小球毛细血管在激活后表达 II 类 MHC 分子。II 类分子在肾微血管内皮细胞上的表达使它们有可能与特异性循环抗体相互作用。我们假设受者 HLA-DQβ10202 表达降低了抗体介导的肾移植排斥反应的可能性。我们发现,80%(25 例)DQ2 阳性单倍型受者未能诱导体液抗体肾移植排斥反应,而 20%(25 例)DQ2 阳性单倍型受者诱导了体液抗体肾移植排斥反应(p=0.008)。相比之下,48%(46 例)DQ2 阴性单倍型受者未能诱导肾移植排斥反应的体液抗体成分,而 52%(46 例)DQ2 阴性单倍型受者诱导了体液抗体介导的肾移植排斥反应。我们的结果表明,表达 DQβ10202 等位基因的受者比表达 DQ1、DQ3 或 DQ4 等位基因的受者更不容易诱导急性肾移植排斥反应的体液抗体成分。受者表达 DQβ1*0202 等位基因可能对急性体液性同种异体移植排斥反应具有保护作用,并可能作为受者选择和急性肾排斥反应发作的适当治疗的未来标准。

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