基于免疫反应检测的免疫抑制调整：一项随机对照试验的结果

Immunosuppression Modifications Based on an Immune Response Assay: Results of a Randomized, Controlled Trial.

作者信息

Ravaioli Matteo, Neri Flavia, Lazzarotto Tiziana, Bertuzzo Valentina Rosa, Di Gioia Paolo, Stacchini Giacomo, Morelli Maria Cristina, Ercolani Giorgio, Cescon Matteo, Chiereghin Angela, Del Gaudio Massimo, Cucchetti Alessandro, Pinna Antonio D

机构信息

1 Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy. 2 Department of General Surgery and Transplantation, Sant'Orsola-Malpighi Hospital, Bologna, Italy. 3 Clinical Unit of Microbiology, University of Bologna, Bologna, Italy.

出版信息

Transplantation. 2015 Aug;99(8):1625-32. doi: 10.1097/TP.0000000000000650.

DOI:10.1097/TP.0000000000000650

PMID:25757214

Abstract

BACKGROUND

An immune function assay shows promise for identifying solid organ recipients at risk for infection or rejection. The following randomized prospective study was designed to assess the clinical benefits of adjusting immunosuppressive therapy in liver recipients based on immune function assay results.

METHODS

Adult liver recipients were randomized to standard practice (control group; n = 102) or serial immune function testing (interventional group; n = 100) performed with a commercially available in vitro diagnostic assay (ImmuKnow; Viracor-IBT Laboratories, Lee's Summit, MO) before transplantation, immediately after surgery and at day 1, weeks 1 to 4, 6, and 8, and months 3 to 6, 9, and 12. The assay was repeated within 7 days of suspected/confirmed rejection/infection and within 1 week after event resolution.

RESULTS

Based on immune function values, tacrolimus doses were reduced 25% when values were less than 130 ng/mL adenosine triphosphate (low immune cell response) and increased 25% when values were greater than 450 ng/mL adenosine triphosphate (strong immune cell response). The 1-year patient survival was significantly higher in the interventional arm (95% vs 82%; P < 0.01) and the incidence of infections longer than 14 days after transplantation was significantly lower among patients in the interventional arm (42.0% vs. 54.9%, P < 0.05). The difference in infection rates was because of lower bacterial (32% vs 46%; P < 0.05) and fungal infection (2% vs 11%; P < 0.05). Among recipients without adverse events, the study group had lower tacrolimus dosages and blood levels.

CONCLUSIONS

Immune function testing provided additional data which helped optimize immunosuppression and improve patient outcomes.

摘要

背景

免疫功能检测对于识别有感染或排斥风险的实体器官接受者具有前景。以下随机前瞻性研究旨在评估根据免疫功能检测结果调整肝移植受者免疫抑制治疗的临床益处。

方法

成年肝移植受者被随机分为标准治疗组（对照组；n = 102）或进行系列免疫功能检测的干预组（n = 100），在移植前、术后即刻、第1天、第1至4周、第6周、第8周以及第3至6个月、第9个月和第12个月使用市售体外诊断检测方法（ImmuKnow；Viracor-IBT Laboratories，密苏里州李 Summit）进行检测。在怀疑/确认排斥/感染后7天内以及事件解决后1周内重复进行检测。

结果

根据免疫功能值，当三磷酸腺苷值低于130 ng/mL（低免疫细胞反应）时，他克莫司剂量降低25%；当三磷酸腺苷值高于450 ng/mL（强免疫细胞反应）时，他克莫司剂量增加25%。干预组的1年患者生存率显著更高（95%对82%；P < 0.01），且干预组患者移植后超过14天的感染发生率显著更低（42.0%对54.9%，P < 0.05）。感染率的差异是由于细菌感染率更低（32%对46%；P < 0.05）和真菌感染率更低（2%对11%；P < 0.05）。在无不良事件的受者中，研究组的他克莫司剂量和血药浓度更低。