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肝移植受者中与排斥反应相关的HLA-DRB1和-DQB1错配导致供体特异性微嵌合体的发展。

Development of donor-specific microchimerism in liver transplant recipient with HLA-DRB1 and -DQB1 mismatch related to rejection episodes.

作者信息

Araújo M B, Leonardi L S, Boin I F S F, Leonardi M I, Magna L A, Donadi E A, Kraemer M H S

机构信息

Immunogenetics Transplant Laboratory, Clinical Pathology Department, School of Medical Sciences, Campinas, SP, Brazil.

出版信息

Transplant Proc. 2004 May;36(4):953-5. doi: 10.1016/j.transproceed.2004.03.097.

DOI:10.1016/j.transproceed.2004.03.097
PMID:15194331
Abstract

Migration of donor-derived cells to recipient tissues after liver transplantation has been suggested as a mechanism to induce and maintain allograft tolerance, although important issues remain including acute rejection posttransplantation mortality, and complications related to immunosuppressive therapy. We therefore examined the relation of rejection to chimerism based upon recipient and donor mismatch of HLA-DRB1 and -DQB1 alleles. Laboratory analysis of peripheral blood was performed before and 10 days to 16 months after liver transplantation in 32 recipients, using ganglion or spleen cell samples of respective donors. DNA was extracted for HLA-DRB1 and DQB1 allele typing using polymerase chain reactions with sequence-specific primers (PCR-SSP). Microchimerism was analyzed through nested PCR. Our results confirmed that patients with one or two mismatched HLA-DRB1 and-DQB1 alleles showed microchimerism and no rejection (P <.05). Microchimerism was present in 71.88% of the patients, and a significant association of rejection P <.05 was found when microchimerism was correlated to graft rejection. These results suggest that the presence of microchimerism may be associated with acceptance, tolerance and survival of the allograft.

摘要

肝移植后供体来源细胞向受体组织的迁移被认为是诱导和维持同种异体移植耐受的一种机制,尽管仍存在一些重要问题,包括移植后急性排斥反应、死亡率以及与免疫抑制治疗相关的并发症。因此,我们基于受体和供体HLA - DRB1和 - DQB1等位基因的错配情况,研究了排斥反应与嵌合体的关系。在32例受体肝移植前以及移植后10天至16个月,使用各自供体的神经节或脾细胞样本进行外周血实验室分析。采用序列特异性引物聚合酶链反应(PCR - SSP)提取DNA进行HLA - DRB1和DQB1等位基因分型。通过巢式PCR分析微嵌合体。我们的结果证实,具有一个或两个HLA - DRB1和 - DQB1等位基因错配的患者表现出微嵌合体且无排斥反应(P <.05)。71.88%的患者存在微嵌合体,当微嵌合体与移植排斥反应相关联时,发现排斥反应有显著相关性(P <.05)。这些结果表明,微嵌合体的存在可能与同种异体移植物的接受、耐受和存活相关。

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