Division of Cardiovascular Medicine, Stanford University, Stanford, CA, USA; Department of Internal Medicine, Chosun University School of Medicine, Gwangju, Republic of Korea.
Division of Cardiovascular Medicine, Stanford University, Stanford, CA, USA.
Int J Cardiol. 2018 Jan 15;251:58-64. doi: 10.1016/j.ijcard.2017.10.060. Epub 2017 Oct 22.
Most immunosuppressive drugs provide targeted immunosuppression by selective inhibition of lymphocyte activation and proliferation. This study evaluated whether a change in the lymphocyte to neutrophil ratio (LNR) is related to acute rejection.
In 74 cardiac transplant recipients peripheral blood lymphocyte and neutrophil counts were measured soon after (baseline) and three, six, and 12months after heart transplantation. The primary endpoint was the incidence of acute rejection.
Significant acute rejection after heart transplantation occurred in 20 patients (27%) during a median follow-up of 49.4 [IQR 37.4-61.1] months. LNR significantly increased over time (0.1149±0.1354 at baseline, 0.2330±0.2266 at 3months, 0.2961±0.2849 at 6months, and 0.3521±0.2383 at 12months; P<0.001), especially during the first 3months in the group without acute rejection. The area under the curve of the change in LNR during the first three months (ΔLNR) for acute rejection was 0.565 (95% CI 0.420 to 0.710, P=0.380) on ROC curve analysis. The best cutoff value of Δ LNR to differentiate those with and without acute rejection was ≤0.046 by ROC curve analysis. Kaplan-Meier analysis revealed that the low ΔLNR group (≤0.046) had a significantly higher rate of acute rejection than the high ΔLNR group (>0.046) (37.5% vs. 19.0%, log-rank: P=0.0358). The low ΔLNR for the first 3months was an independent predictor of clinically significant acute rejection after adjusting for cytomegalovirus donor seropositive and recipient seronegative.
The results of this study suggest that ΔLNR over the first 3months after heart transplantation is a strong and independent predictor of acute rejection after heart transplantation. ΔLNR can be used as an early biomarker for predicting of acute rejection after heart transplantation.
大多数免疫抑制剂通过选择性抑制淋巴细胞激活和增殖来提供靶向免疫抑制。本研究评估了淋巴细胞与中性粒细胞比值(LNR)的变化是否与急性排斥反应有关。
在 74 例心脏移植受者中,在心脏移植后不久(基线)以及 3、6 和 12 个月时测量外周血淋巴细胞和中性粒细胞计数。主要终点是急性排斥反应的发生率。
中位随访 49.4 [IQR 37.4-61.1] 个月期间,20 例(27%)患者发生显著的心脏移植后急性排斥反应。LNR 随时间显著增加(基线时为 0.1149±0.1354,3 个月时为 0.2330±0.2266,6 个月时为 0.2961±0.2849,12 个月时为 0.3521±0.2383;P<0.001),尤其是在无急性排斥反应组的前 3 个月。在第 1 至 3 个月期间 LNR 变化(ΔLNR)的曲线下面积(AUC)在 ROC 曲线分析中为 0.565(95%CI 0.420 至 0.710,P=0.380)。通过 ROC 曲线分析,ΔLNR 区分有和无急性排斥反应的最佳截断值为≤0.046。Kaplan-Meier 分析显示,低ΔLNR 组(≤0.046)的急性排斥反应发生率明显高于高ΔLNR 组(>0.046)(37.5%比 19.0%,对数秩检验:P=0.0358)。在调整巨细胞病毒供者血清阳性和受者血清阴性后,前 3 个月的低ΔLNR 是心脏移植后临床显著急性排斥反应的独立预测因子。
本研究结果表明,心脏移植后前 3 个月的ΔLNR 是心脏移植后急性排斥反应的强且独立的预测因子。ΔLNR 可作为心脏移植后急性排斥反应的早期生物标志物。