对血清阳性心脏移植受者的巨细胞病毒特异性抗体和 T 细胞水平进行同步监测。

Simultaneous monitoring of cytomegalovirus-specific antibody and T-cell levels in seropositive heart transplant recipients.

机构信息

Transplant Immunology Group, Clinical Immunology Department, Gregorio Marañón Hospital, Dr Esquerdo 46, 28007, Madrid, Spain.

出版信息

J Clin Immunol. 2012 Aug;32(4):809-19. doi: 10.1007/s10875-012-9670-7. Epub 2012 Feb 29.

DOI:10.1007/s10875-012-9670-7

PMID:22371292

Abstract

PURPOSE

Human cytomegalovirus (CMV) active infection (CMV infection) poses serious risks to CMV-seropositive heart transplant recipients. We evaluated the usefulness of simultaneous assessment of CMV-specific values for parameters of the humoral (antibodies) and cellular (CD4+ and CD8+ T-cells) immune responses in the identification of heart recipients at risk of developing CMV infection after transplantation.

METHODS

We prospectively studied 38 CMV-seropositive heart recipients. Anti-CMV antibody titers were assessed using enzyme-linked immunosorbent assays. CD4+ and CD8+ T-cell responses to overlapping peptide pools of the CMV proteins pp65 and immediate early protein-1 (IE1) were evaluated by flow cytometry. Immunological studies were performed before transplantation and at 30 days after transplantation. Patients with CMV infection were compared with heart recipients without CMV infection.

RESULTS

During the 6-month follow-up period, 13 (34.2%) patients developed CMV infection. At baseline, the mean anti-CMV-IgG antibody titer was lower in patients who developed CMV infection. This difference remained at 30 days after transplantation. One month after transplantation, the mean percentage of IE1-specific CD8+ T cells that are IFNg-positive (CD8/IFNg + IE1) was lower in CMV-infected patients. The predictive value of these variables at 30 days was increased when they were combined. Cox regression analysis revealed an association between the risk of developing CMV infection and the combination marker (low anti-CMV titer [<16,100] and low CD8/IFNg + IE1 percentages [<0.40%], relative hazard, 6.07; p = 0.019). The combination marker remained significant after adjustment for clinical variables.

CONCLUSIONS

This novel approach of a simultaneous assessment of specific anti-CMV antibody titers and CD8/IFNg + IE1 percentages might help identify heart transplant recipients with an increased risk of developing CMV infection.

摘要

目的

人巨细胞病毒（CMV）活性感染（CMV 感染）对 CMV 血清阳性心脏移植受者构成严重威胁。我们评估了同时评估 CMV 特异性参数对体液（抗体）和细胞（CD4+和 CD8+T 细胞）免疫反应的价值，以确定移植后发生 CMV 感染风险的心脏受者。

方法

我们前瞻性研究了 38 例 CMV 血清阳性心脏受者。使用酶联免疫吸附试验评估抗 CMV 抗体滴度。通过流式细胞术评估 CMV 蛋白 pp65 和即刻早期蛋白-1（IE1）的重叠肽池对 CD4+和 CD8+T 细胞的反应。免疫研究在移植前和移植后 30 天进行。将发生 CMV 感染的患者与无 CMV 感染的心脏受者进行比较。

结果

在 6 个月的随访期间，13 例（34.2%）患者发生 CMV 感染。在基线时，发生 CMV 感染的患者的平均抗 CMV-IgG 抗体滴度较低。这种差异在移植后 30 天仍然存在。移植后 1 个月，CMV 感染患者的 IE1 特异性 CD8+T 细胞中 IFNg 阳性（CD8/IFNg+IE1）的平均百分比较低。这些变量在 30 天时的预测值增加时结合在一起。Cox 回归分析显示，发生 CMV 感染的风险与组合标志物（低抗 CMV 滴度 [<16,100]和低 CD8/IFNg+IE1 百分比 [<0.40%]）之间存在关联，相对危险度为 6.07；p=0.019）。在调整临床变量后，组合标志物仍然具有统计学意义。