原位肝移植后，急性细胞排斥反应与基质金属蛋白酶-2基因型嵌合现象有关。

Acute cellular rejection is associated with matrix metalloproteinase-2 genotype chimerism after orthotopic liver transplantation.

作者信息

Korkmaz K S, Ten Hove W R, de Rooij B-J F, van Hoek B, van der Reijden J J, Coenraad M J, Dubbeld J, Verspaget H W

机构信息

Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, The Netherlands.

出版信息

Transplant Proc. 2013 Mar;45(2):558-63. doi: 10.1016/j.transproceed.2012.12.002.

DOI:10.1016/j.transproceed.2012.12.002

PMID:23498792

Abstract

PURPOSE

Chimerism in transplantation medicine refers to the coexistence of cells of donor and recipient origin. Their existence in relation to possible pathological mechanisms remains largely unknown. We used donor-recipient mismatches for matrix metalloproteinases (MMP) gene polymorphisms in liver biopsies and in blood as a marker for chimerism after orthotopic liver transplantation (OLT). The second aim of this study was to evaluate these polymorphisms in relation to clinical outcome such as ischemia-reperfusion injury (IRI) and acute cellular rejection (ACR).

METHODS

MMP-2 and MMP-9 promoter polymorphism donor-recipient mismatches were determined in 147 OLT patients. The relationship between these MMP polymorphism mismatches in donor and recipient DNA with the development of IRI and ACR after OLT was evaluated. Liver biopsy specimens and peripheral blood samples were subsequently evaluated for the presence of chimerism, also in relation to these complications.

RESULTS

MMP polymorphism donor-recipient mismatches were found in 53.7% (MMP-2) and 35.5% (MMP-9) of the OLT patients but no relation was observed with IRI or ACR. Chimerism in liver biopsy specimens was found to be present in 28.8% (MMP-2) and 16.2% (MMP-9) of the cases. Liver chimerism in MMP-2 was found to be significantly associated with ACR after OLT (χ(2) 6.4, P = .01). Multivariate analysis revealed MMP-2 chimerism to be an independent risk factor for ACR after OLT even adjusted for Model for End-stage Liver Disease score (hazard ratio = 3.83, P = .03). In addition, evidence of donor chimerism was found in peripheral blood samples of the recipients in some cases.

CONCLUSION

Chimerism after OLT can be found in liver biopsy specimens and in peripheral blood. MMP donor-recipient polymorphism mismatches are good markers for assessing chimerism after OLT. In the multivariate analysis, liver chimerism in MMP-2 was found to be significantly associated with the development of ACR after OLT.

摘要

目的

移植医学中的嵌合体是指供体来源细胞和受体来源细胞的共存。其与可能的病理机制之间的关系在很大程度上仍不清楚。我们将肝活检组织和血液中基质金属蛋白酶（MMP）基因多态性的供受体错配作为原位肝移植（OLT）后嵌合体的一个标志物。本研究的第二个目的是评估这些多态性与诸如缺血再灌注损伤（IRI）和急性细胞排斥反应（ACR）等临床结局之间的关系。

方法

测定了147例OLT患者的MMP-2和MMP-9启动子多态性供受体错配情况。评估了供体和受体DNA中这些MMP多态性错配与OLT后IRI和ACR发生之间的关系。随后还评估了肝活检标本和外周血样本中嵌合体的存在情况，以及其与这些并发症的关系。

结果

在53.7%（MMP-2）和35.5%（MMP-9）的OLT患者中发现了MMP多态性供受体错配，但未观察到其与IRI或ACR有关。在28.8%（MMP-2）和16.2%（MMP-9）的病例中发现肝活检标本中存在嵌合体。发现MMP-2的肝嵌合体与OLT后的ACR显著相关（χ(2)=6.4，P = 0.01）。多变量分析显示，即使在校正终末期肝病模型评分后，MMP-2嵌合体仍是OLT后ACR的一个独立危险因素（风险比 = 3.83，P = 0.03）。此外，在某些病例的受体外周血样本中发现了供体嵌合体的证据。