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韩国活体肝移植中人类白细胞抗原-C基因型与杀伤细胞免疫球蛋白样受体-配体匹配情况

Human Leukocyte Antigen-C Genotype and Killer Immunoglobulin-like Receptor-Ligand Matching in Korean Living Donor Liver Transplantation.

作者信息

Lee Hyeyoung, Park Ki Hyun, Park Hye Sun, Ryu Ji Hyeong, Lim Jihyang, Kim Yonggoo, Na Gun Hyung, Kim Dong Goo, Oh Eun Jee

机构信息

Department of Laboratory Medicine, Seoul St. Mary's Hospital, College of Medicine, the Catholic University of Korea, Seoul, Korea.

Department of Biomedical Science, Graduate School, the Catholic University of Korea, Seoul, Korea.

出版信息

Ann Lab Med. 2017 Jan;37(1):45-52. doi: 10.3343/alm.2017.37.1.45.

Abstract

BACKGROUND

The interaction between killer immunoglobulin-like receptors (KIRs) and HLA class I regulates natural killer (NK) cell cytotoxicity and function. The impact of NK cell alloreactivity through KIR in liver transplantation remains unelucidated. Since the frequency of HLA-C and KIR genotypes show ethnic differences, we assessed the impact of HLA-C, KIR genotype, or KIR-ligand mismatch on the allograft outcome of Korean liver allografts.

METHODS

One hundred eighty-two living donor liver transplant patients were studied. Thirty-five patients (19.2%) had biopsy-confirmed acute rejection (AR), and eighteen (9.9%) had graft failure. The HLA-C compatibility, KIR genotypes, ligand-ligand, and KIR-ligand matching was retrospectively investigated for association with allograft outcomes.

RESULTS

Homozygous C1 ligands were predominant in both patients and donors, and frequency of the HLA-C2 allele in Koreans was lower than that in other ethnic groups. Despite the significantly lower frequency of the HLA-C2 genotype in Koreans, donors with at least one HLA-C2 allele showed higher rates of AR than donors with no HLA-C2 alleles (29.2% vs 15.7%, P=0.0423). Although KIR genotypes also showed ethnic differences, KIR genotypes and the number of activating KIR/inhibitory KIR were not associated with the allograft outcome. KIR-ligand mismatch was expected in 31.6% of Korean liver transplants and had no impact on AR or graft survival.

CONCLUSIONS

This study could not confirm the clinical impact of KIR genotypes and KIR-ligand mismatch. However, we demonstrated that the presence of HLA-C2 allele in the donor influenced AR of Korean liver allografts.

摘要

背景

杀伤细胞免疫球蛋白样受体(KIR)与I类人类白细胞抗原(HLA)之间的相互作用调节自然杀伤(NK)细胞的细胞毒性和功能。KIR介导的NK细胞同种异体反应性在肝移植中的影响仍不明确。由于HLA - C和KIR基因型的频率存在种族差异,我们评估了HLA - C、KIR基因型或KIR配体错配对韩国肝移植同种异体移植物结局的影响。

方法

对182例活体肝移植患者进行研究。35例患者(19.2%)经活检证实发生急性排斥反应(AR),18例(9.9%)发生移植物功能衰竭。回顾性研究HLA - C相容性、KIR基因型、配体 - 配体以及KIR - 配体匹配情况与同种异体移植物结局的相关性。

结果

纯合C1配体在患者和供体中均占主导地位,韩国人中HLA - C2等位基因的频率低于其他种族。尽管韩国人中HLA - C2基因型的频率显著较低,但至少有一个HLA - C2等位基因的供体发生AR的比例高于无HLA - C2等位基因的供体(29.2%对15.7%,P = 0.0423)。虽然KIR基因型也存在种族差异,但KIR基因型以及激活型KIR/抑制型KIR的数量与同种异体移植物结局无关。预计31.6%的韩国肝移植存在KIR配体错配,且对AR或移植物存活无影响。

结论

本研究未能证实KIR基因型和KIR配体错配的临床影响。然而,我们证明了供体中HLA - C2等位基因的存在会影响韩国肝移植同种异体移植物的AR。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a617/5107617/8e1aa90b3aa4/alm-37-45-g001.jpg

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