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活体供肝移植后急性细胞排斥反应中的细胞因子基因多态性:155对供受者配对分析

Cytokine gene polymorphisms in acute cellular rejection following living donor liver transplantation: analysis of 155 donor-recipient pairs.

作者信息

Kamei Hideya, Masuda Satohiro, Nakamura Taro, Ishigami Masatoshi, Fujimoto Yasuhiro, Ogura Yasuhiro, Oike Fumitaka, Takada Yasutsugu, Hamajima Nobuyuki

机构信息

Department of Transplantation Surgery, Nagoya University, 65 Tsurumai, Showa, Nagoya, 466-8550, Japan.

Department of Pharmacy, Faculty of Medicine, Kyoto University, Kyoto, Japan.

出版信息

Hepatol Int. 2013 Jul;7(3):916-22. doi: 10.1007/s12072-013-9443-2. Epub 2013 Jul 31.

Abstract

PURPOSE

Despite improvements in immunosuppressive therapy, acute cellular rejection (ACR) remains an important cause of graft loss in patients undergoing liver transplantation. Recently, associations between cytokine gene polymorphisms in recipients and the occurrence of ACR have been reported. However, most studies did not investigate gene polymorphisms in donors or were limited by the number of cases investigated.

METHODS

We examined 155 living donor liver transplantation (LDLT) patients treated at Nagoya University or Kyoto University from 2004 to 2009. The following gene polymorphisms in recipients and donors were analyzed: tumor necrosis factor A (TNF-A) T-1031C, interleukin 2 (IL-2) T-330G, IL-10C-819T, IL-13C-1111T, and transforming growth factor B (TGF-B) T29C.

RESULTS

Forty-seven recipients (30.3 %) developed early ACR. Of the investigated gene polymorphisms, the IL-13 -1111C/C genotype in recipients was significantly associated with a higher incidence of ACR relative to the other two genotypes (OR = 2.64, 95 % CI 1.19-5.86, p = 0.017), while we showed the lack of association between investigated gene polymorphisms in donors and ACR incidence.

CONCLUSION

The IL-13 -1111C/C genotype in recipients might be a risk factor for ACR in LDLT, and this might contribute to individualized immunosuppression strategies for recipients. On the other hand, the current study showed no associations of cytokine gene polymorphisms in donors with ACR incidence.

摘要

目的

尽管免疫抑制治疗有所改进,但急性细胞排斥反应(ACR)仍是肝移植患者移植物丢失的重要原因。最近,有报道称受者细胞因子基因多态性与ACR的发生之间存在关联。然而,大多数研究并未调查供者的基因多态性,或者受所研究病例数量的限制。

方法

我们对2004年至2009年在名古屋大学或京都大学接受治疗的155例活体供肝移植(LDLT)患者进行了研究。分析了受者和供者的以下基因多态性:肿瘤坏死因子A(TNF-A)T-1031C、白细胞介素2(IL-2)T-330G、IL-10C-819T、IL-13C-1111T和转化生长因子B(TGF-B)T29C。

结果

47例受者(30.3%)发生早期ACR。在所研究的基因多态性中,与其他两种基因型相比,受者的IL-13 -1111C/C基因型与ACR的较高发生率显著相关(OR = 2.64,95%CI 1.19 - 5.86,p = 0.017),而我们发现供者所研究的基因多态性与ACR发生率之间缺乏关联。

结论

受者的IL-13 -1111C/C基因型可能是LDLT中ACR的一个危险因素,这可能有助于制定受者的个体化免疫抑制策略。另一方面,目前的研究表明供者细胞因子基因多态性与ACR发生率无关。

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