CAJ | 학술논문

目的：探讨肝移植术后患者外周血辅助性T （Th）17细胞（CD4＋IL-17＋T淋巴细胞）与急性排斥反应的关系。方法本文研究对象为2008年6月至2012年12月在首都医科大学附属北京朝阳医院肝胆胰脾外科因良性终末期肝病行原位肝移植术的76例患者。根据患者术后有否发生急性排斥反应，分为排斥组（17例）和非排斥组（59例）。所有患者均按常规定期随访。记录患者排斥反应发生情况及治疗经过。排斥组患者发生急性排斥反应时给予肝穿刺活组织检查确定排斥反应严重程度。所有患者分别于肝移植术前、出院后1年内定期（间隔3～6个月）、或急性排斥反应治疗前和缓解后（3～6个月），检测外周血CD4＋IL-17＋T淋巴细胞占CD4＋T淋巴细胞百分比（CD4＋IL-17＋T％）。比较两组患者各时间点的 CD4＋IL-17＋T％。分析 CD4＋IL-17＋T％与排斥活动指数（RAI）、免疫抑制剂血药浓度的相关性。结果急性排斥反应发生在术后0.7～12.0个月，中位数2.5个月。肝移植术后，与非排斥组比较，排斥组患者CD4＋IL-17＋T％明显升高[（1.79±0.44）％比（2.56±0.43）％，P＜0.001]。排斥组患者发生急性排斥反应时，CD4＋IL-17＋T％均较未发生急性排斥反应时明显升高[（2.56±0.43）％比（1.50±0.25）％，P＜0.001）]。非排斥组患者不同时间点的CD4＋IL-17＋T％变化不明显（P＞0.05）。排斥组患者发生急性排斥反应时的CD4＋IL-17＋T％与RAI呈正相关（r＝0.72，P＝0.001）。排斥组和非排斥组患者他克莫司、环孢素血药浓度与CD4＋IL-17＋T％无明显相关性（r＝0.21，-0.13；均为P＞0.05）。结论外周血CD4＋IL-17＋T％可作为诊断和评估肝移植术后急性排斥反应严重程度的监测指标，外周血CD4＋IL-17＋T％升高提示急性排斥反应严重。
목적：탐토간이식술후환자외주혈보조성T （Th）17세포（CD4＋IL-17＋T림파세포）여급성배척반응적관계。방법본문연구대상위2008년6월지2012년12월재수도의과대학부속북경조양의원간담이비외과인량성종말기간병행원위간이식술적76례환자。근거환자술후유부발생급성배척반응，분위배척조（17례）화비배척조（59례）。소유환자균안상규정기수방。기록환자배척반응발생정황급치료경과。배척조환자발생급성배척반응시급여간천자활조직검사학정배척반응엄중정도。소유환자분별우간이식술전、출원후1년내정기（간격3～6개월）、혹급성배척반응치료전화완해후（3～6개월），검측외주혈CD4＋IL-17＋T림파세포점CD4＋T림파세포백분비（CD4＋IL-17＋T％）。비교량조환자각시간점적 CD4＋IL-17＋T％。분석 CD4＋IL-17＋T％여배척활동지수（RAI）、면역억제제혈약농도적상관성。결과급성배척반응발생재술후0.7～12.0개월，중위수2.5개월。간이식술후，여비배척조비교，배척조환자CD4＋IL-17＋T％명현승고[（1.79±0.44）％비（2.56±0.43）％，P＜0.001]。배척조환자발생급성배척반응시，CD4＋IL-17＋T％균교미발생급성배척반응시명현승고[（2.56±0.43）％비（1.50±0.25）％，P＜0.001）]。비배척조환자불동시간점적CD4＋IL-17＋T％변화불명현（P＞0.05）。배척조환자발생급성배척반응시적CD4＋IL-17＋T％여RAI정정상관（r＝0.72，P＝0.001）。배척조화비배척조환자타극막사、배포소혈약농도여CD4＋IL-17＋T％무명현상관성（r＝0.21，-0.13；균위P＞0.05）。결론외주혈CD4＋IL-17＋T％가작위진단화평고간이식술후급성배척반응엄중정도적감측지표，외주혈CD4＋IL-17＋T％승고제시급성배척반응엄중。
To study the relationship between T helper (Th) 17 cell [CD4 +interleukin (IL)-17 +T lymphocytes]in peripheral blood and acute rejection in patients after liver transplantation.Methods A total of 76 patients receiving orthotopic liver transplantation (OLT)for benign end-stage liver diseases in Department of Hepatobiliary and Pancreas-Spleen Surgery,Affiliated Beijing Chaoyang Hospital of Capital Medical University from June 2008 to December 2012 were included in this study. According to whether the acute rejection occurred after operation,the patients were divided into rejection group (n=17)and non-rejection group (n=59). All the patients were followed up regularly by routine. The incidence of rejection and the treatment of patients were recorded. Patients in the rejection group received liver biopsy when suffered acute rejection to decide the severity. The percentage of CD4 +IL-17 +T lymphocytes to CD4 +T lymphocytes (CD4 +IL-17 +T%)in peripheral blood in all patients was measured at different time points:pre-OLT,at regular intervals (3-6 months)within 1 year after hospital discharge or before the treatment of acute rejection and after the remission (3-6 months). The CD4 +IL-17 +T% of every time point were compared between two groups.The correlations of CD4 +IL-17 +T% with the rejection activity index (RAI ), blood concentration of immunosuppressor were analyzed.Results The acute rejection occurred in 0.7-12.0 (median:2.5 ) months after OLT. The CD4 +IL-17 +T% in the rejection group increased significantly compared with that in the non-rejection group after OLT [(2.56 ±0.43)%vs. (1.79 ±0.44)%,P<0.001]. In the rejection group,the CD4 +IL-17 +T% increased significantly when acute rejection occurred compared with that when acute rejection had not occurred [(2.56 ±0.43)%vs. (1.50 ±0.25)%,P<0.001)]. The variation of CD4 +IL-17 +T%was not obvious at different time points in non-rejection group (P >0.05 ). The CD4 +IL-17 +T% was positively correlated with RAI when acute rejection occurred in the rejection group (r=0.72,P=0.001 ).The blood concentration of tacrolimus,cyclosporin in rejection and non-rejection group were not correlated with CD4 +IL-17 +T% (r=0.21,-0.13;both in P>0.05). Conclusions CD4 +IL-17 +T%in peripheral blood can be used as a monitoring index for deciding and assessing severity of acute rejection after OLT. The increase of CD4 +IL-17 +T% in peripheral blood indicates a severe acute rejection.