Immunology Department, Hospital Universitario Central de Asturias (HUCA), Oviedo, Spain.
Department of Microbiology, HUCA, Oviedo, Spain.
PLoS One. 2018 Apr 11;13(4):e0194789. doi: 10.1371/journal.pone.0194789. eCollection 2018.
Anti-CMV (cytomegalovirus) antibody titers are related to immune alterations and increased risk of mortality. To test whether they represent a marker of infection history, we analyzed the effect of viral reactivations on the production of specific antibodies in kidney transplant patients. We quantified CMV-DNAemia and antibody titers in 58 kidney transplant patients before transplantation and during a follow-up of 315 days (standard deviation, SD: 134.5 days). In order to calculate the intensity of the infection, we plotted the follow-up time of the infection on the x-axis and the number of DNA-CMV copies on the y-axis and calculated the area under the curve (CMV-AUC). The degree of T-lymphocyte differentiation was analyzed with flow cytometry, the cells were labelled with different monoclonal antibodies in order to distinguish their differentiation state, from naive T-cells to senescent T-cells. Peak viremia was significantly higher in patients experiencing a primary infection (VI) compared to patients experiencing viral reactivation (VR). Our data indicate that the overall CMV viral load over the course of a primary infection is significantly higher than in a reactivation of a previously established infection. Whereas patients who experienced an episode of CMV reactivation during the course of our observation showed increased levels of CMV-specific antibodies, patients who did not experience CMV reactivation (WVR) showed a drop in CMV antibody levels that corresponds to an overall drop in antibody levels, probably due to the continuing immunosuppression after the renal transplant. We found a positive correlation between the CMV viremia over the course of the infection or reactivation and the CMV-specific antibody titers in the examined patients. We also observed a positive correlation between anti-CMV titers and T-cell differentiation. In conclusion, our data show that anti-CMV antibody titers are related to the course of CMV infection in kidney transplant patients.
抗 CMV（巨细胞病毒）抗体滴度与免疫改变和死亡率增加有关。为了测试它们是否代表感染史的标志物，我们分析了病毒再激活对肾移植患者特异性抗体产生的影响。我们在移植前和 315 天的随访中（标准差，SD：134.5 天）对 58 名肾移植患者进行了 CMV-DNAemia 和抗体滴度的定量检测。为了计算感染的强度，我们将感染的随访时间绘制在 x 轴上，将 DNA-CMV 拷贝数绘制在 y 轴上，并计算曲线下面积（CMV-AUC）。通过流式细胞术分析 T 淋巴细胞的分化程度，用不同的单克隆抗体对细胞进行标记，以区分其分化状态，从幼稚 T 细胞到衰老 T 细胞。初次感染（VI）患者的病毒血症峰值明显高于病毒再激活（VR）患者。我们的数据表明，原发性感染过程中的总体 CMV 病毒载量明显高于先前建立的感染再激活。而在我们的观察过程中经历 CMV 再激活的患者表现出 CMV 特异性抗体水平升高，而未经历 CMV 再激活（WVR）的患者则表现出 CMV 抗体水平下降，这与抗体水平的整体下降相对应，可能是由于肾移植后持续的免疫抑制所致。我们发现感染或再激活过程中 CMV 病毒血症与受检患者的 CMV 特异性抗体滴度之间存在正相关。我们还观察到抗 CMV 滴度与 T 细胞分化之间存在正相关。总之，我们的数据表明，肾移植患者的抗 CMV 抗体滴度与 CMV 感染的过程有关。
