细胞免疫预测肾移植中巨细胞病毒感染的风险：一项前瞻性、干预性、多中心临床试验。
Cellular Immunity to Predict the Risk of Cytomegalovirus Infection in Kidney Transplantation: A Prospective, Interventional, Multicenter Clinical Trial.
机构信息
Experimental Nephrology Laboratory, Bellvitge Biomedical Research Institute, IDIBELL, Hospitalet de Llobregat, Spain.
Kidney Transplant Unit, Nephrology Department, Bellvitge University Hospital, Barcelona, Spain.
出版信息
Clin Infect Dis. 2020 Dec 3;71(9):2375-2385. doi: 10.1093/cid/ciz1209.
BACKGROUND
Improving cytomegalovirus (CMV) immune-risk stratification in kidney transplantation is highly needed to establish guided preventive strategies.
METHODS
This prospective, interventional, multicenter clinical trial assessed the value of monitoring pretransplant CMV-specific cell-mediated immunity (CMI) using an interferon-γ release assay to predict CMV infection in kidney transplantation. One hundred sixty donor/recipient CMV-seropositive (D+/R+) patients, stratified by their baseline CMV (immediate-early protein 1)-specific CMI risk, were randomized to receive either preemptive or 3-month antiviral prophylaxis. Also, 15-day posttransplant CMI risk stratification and CMI specific to the 65 kDa phosphoprotein (pp65) CMV antigen were investigated. Immunosuppression consisted of basiliximab, tacrolimus, mycophenolate mofetil, and corticosteroids in 80% of patients, whereas 20% received thymoglobulin induction therapy.
RESULTS
Patients at high risk for CMV based on pretransplant CMI developed significantly higher CMV infection rates than those deemed to be at low risk with both preemptive (73.3% vs 44.4%; odds ratio [OR], 3.44 [95% confidence interval {CI}, 1.30-9.08]) and prophylaxis (33.3% vs 4.1%; OR, 11.75 [95% CI, 2.31-59.71]) approaches. The predictive capacity for CMV-specific CMI was only found in basiliximab-treated patients for both preemptive and prophylaxis therapy. Fifteen-day CMI risk stratification better predicted CMV infection (81.3% vs 9.1%; OR, 43.33 [95% CI, 7.89-237.96]).
CONCLUSIONS
Pretransplant CMV-specific CMI identifies D+/R+ kidney recipients at high risk of developing CMV infection if not receiving T-cell-depleting antibodies. Monitoring CMV-specific CMI soon after transplantation further defines the CMV infection prediction risk. Monitoring CMV-specific CMI may guide decision making regarding the type of CMV preventive strategy in kidney transplantation.
CLINICAL TRIALS REGISTRATION
NCT02550639.
背景
在肾移植中，提高巨细胞病毒（CMV）免疫风险分层对于建立有针对性的预防策略非常重要。
方法
这项前瞻性、干预性、多中心临床试验评估了使用干扰素-γ释放试验监测移植前 CMV 特异性细胞介导免疫（CMI）以预测肾移植中 CMV 感染的价值。160 例供体/受者 CMV 阳性（D+/R+）患者根据其基线 CMV（早期蛋白 1）特异性 CMI 风险进行分层，随机接受抢先或 3 个月抗病毒预防。还研究了移植后 15 天的 CMI 风险分层和针对 65 kDa 磷酸蛋白（pp65）CMV 抗原的 CMI 特异性。免疫抑制方案包括巴利昔单抗、他克莫司、霉酚酸酯和皮质类固醇，80%的患者接受该方案，而 20%的患者接受胸腺球蛋白诱导治疗。
结果
基于移植前 CMI 处于高风险的患者与低风险患者相比，无论是抢先治疗（73.3% vs 44.4%；比值比 [OR]，3.44 [95%置信区间 {CI}，1.30-9.08]）还是预防治疗（33.3% vs 4.1%；OR，11.75 [95% CI，2.31-59.71]），CMV 感染率均显著更高。仅在接受巴利昔单抗治疗的患者中，CMV 特异性 CMI 对抢先和预防治疗均具有预测能力。移植后 15 天的 CMI 风险分层更好地预测了 CMV 感染（81.3% vs 9.1%；OR，43.33 [95% CI，7.89-237.96]）。
结论
在未接受 T 细胞耗竭抗体治疗的情况下，移植前 CMV 特异性 CMI 可识别 D+/R+肾移植受者发生 CMV 感染的高风险。移植后早期监测 CMV 特异性 CMI 可进一步确定 CMV 感染预测风险。监测 CMV 特异性 CMI 可能有助于指导肾移植中 CMV 预防策略的选择。
临床试验注册
NCT02550639。
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