Mizuno Shugo, Nakatani Kaname, Muraki Yuichi, Tanemura Akihiro, Azumi Yoshinori, Kuriyama Naohisa, Ohsawa Ichiro, Kishiwada Masashi, Usui Masanobu, Sakurai Hiroyuki, Tabata Masami, Okuda Masahiro, Nobori Tsutomu, Isaji Shuji
mizunos @clin.medic.mie-u.ac.jpDepartment of Hepatobiliary Pancreatic and Transplant Surgery, Mie University School of Medicine, Tsu, Mie, Japan.
Ann Transplant. 2013 Jul 11;18:349-57. doi: 10.12659/AOT.883974.
The aim of this study is to evaluate whether the combination of the ImmuKnow assay (IMK) and cytochrome P450 3A5 (CYP3A5) genotype assay is useful for identifying the risk of morbidity and mortality in living donor liver transplantation (LDLT) patients, and also to investigate the optimal cutoff value of IMK level of immune status.
Sixty six LDLT patients, who were randomly screened by using IMK between March 2002 and June 2011, were divided into 2 groups: patients in whom at least 1 IMK value was <175 ng/mL (Group A, n=16) and patients in whom all IMK values were >175 ng/mL (Group B, n=50). Both donors and recipients were evaluated for the CYP3A5 genotype.
The frequencies of cytomegalovirus and bacterial infection in Group A were significantly higher than those in Group B (P<0.001). The short term mortality was 4 (25.0%) in Group A and none in Group B, and the IMK level in all four cases became <100 ng/mL at least one time before death. The rate of CYP3A5*1 allele (expressors) among recipients was significantly higher in Group A than in Group B (63.6% vs. 22.2%, P=0.0147). The rates of CMV infection and bacterial infection, and the IMK levels was significantly higher in recipients with expressors (p=0.0216, p=0.0332, and p=0.0433, respectively).
The combination of the IMK and CYP3A5 genotype assay is useful for monitoring immune status after LDLT, and the IMK level <100 ng/ml might be the critical level to make a recovery from the severe immunesupressive condition.
本研究旨在评估免疫状态检测(ImmuKnow检测,IMK)与细胞色素P450 3A5(CYP3A5)基因分型检测相结合是否有助于识别活体肝移植(LDLT)受者的发病和死亡风险,并探讨免疫状态IMK水平的最佳临界值。
对2002年3月至2011年6月间通过IMK随机筛选的66例LDLT受者进行分组:至少1次IMK值<175 ng/mL的受者为A组(n = 16),所有IMK值均>175 ng/mL的受者为B组(n = 50)。对供者和受者均进行CYP3A5基因分型评估。
A组巨细胞病毒和细菌感染的发生率显著高于B组(P<0.001)。A组短期死亡率为4例(25.0%),B组无死亡病例,且4例死亡病例在死亡前至少有1次IMK水平降至<100 ng/mL。A组受者中CYP3A5*1等位基因(表达者)的比例显著高于B组(63.6%对22.2%,P = 0.0147)。表达者受者的巨细胞病毒感染率、细菌感染率及IMK水平均显著更高(分别为P = 0.0216、P = 0.0332和P = 0.0433)。
IMK与CYP3A5基因分型检测相结合有助于监测LDLT后的免疫状态,IMK水平<100 ng/ml可能是从严重免疫抑制状态恢复的临界水平。