Background

Human Cytomegalovirus (HCMV) may cause severe infections in lung-transplant recipients (LTRs). The impact of the host antibody (AB) -dependent cytotoxicity (ADCC) on HCMV is still unclear. We therefore analysed the AB-response against HCMV glycoprotein B (gB) and the pentameric complex (PC) and the ADCC response in HCMV-seropositive (R+) LTRs and in seronegative recipients of positive organs (D+/R-).

Methods

Plasma samples were collected from 35 R+ and 28 D+/R- LTRs for one (R+) or two (D+/R-) years post-transplantation, and from 114 healthy control persons. PC- and gB-specific ABs were assessed by ELISA. ADCC was analysed by focal expansion (FEA) and CD107 cytotoxicity assays.

Results

In R+ LTRs significantly higher gB-specific AB levels developed within one year post-transplantation than in controls (IgG1:p<0.001, IgG3:p<0.001). Also, higher levels of ADCC were observed by FEA and CD107 assay in R+ patients compared to controls (p<0.001). In 23 D+R- patients HCMV-specific ABs developed. ADCC became detectable 3 months post-transplantation in these, with higher ADCC observed in viremic patients. Depletion of gB and PC- specific ABs revealed, that especially gB- specific Abs were associated with the ADCC response.

Conclusions

We show that a strong ADCC is elicited after transplantation and is especially based on gB-specific ABs.

中文翻译：

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人巨细胞病毒（HCMV）特异性抗体应答和针对肺移植后针对HCMV的抗体依赖性细胞毒性的发展。

背景

人巨细胞病毒（HCMV）可能会导致肺移植受者（LTR）受到严重感染。宿主抗体（AB）依赖性细胞毒性（ADCC）对HCMV的影响仍不清楚。因此，我们分析了针对HCMV糖蛋白B（gB）和五聚体复合物（PC）的AB反应以及HCMV血清阳性（R +）LTR和阳性器官的血清阴性受体（D + / R-）中的ADCC反应。

方法

在移植后一年（R +）或两年（D + / R-）中，从114名健康对照者的35个R +和28个D + / R- LTR中收集血浆样品。通过ELISA评估PC和gB特异性的AB。ADCC通过病灶扩展（FEA）和CD107细胞毒性分析进行了分析。

结果

在R + LTR中，移植后一年内出现的gB特异性AB水平明显高于对照组（IgG1：p <0.001，IgG3：p <0.001）。此外，与对照组相比，RFE患者通过FEA和CD107分析观察到了更高水平的ADCC（p <0.001）。在23名D + R-患者中，产生了HCMV特异性AB。这些患者在移植后3个月可检测到ADCC，而病毒血症患者的ADCC更高。显示出gB和PC特异性AB的耗竭，尤其是gB特异性Ab与ADCC反应有关。

结论

我们显示出强大的ADCC移植后引发，尤其是基于gB特异性AB。