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Pre-transplant assessment of pp65-specific CD4 T cell responses identifies CMV-seropositive patients treated with rATG at risk of late onset infection.
Clinical Immunology ( IF 8.6 ) Pub Date : 2019-12-28 , DOI: 10.1016/j.clim.2019.108329
Maria O López-Oliva 1 , Virginia Martínez 2 , Aranzazu Rodríguez-Sanz 2 , Laura Álvarez 1 , M José Santana 1 , Rafael Selgas 3 , Carlos Jiménez 1 , Teresa Bellón 2
Affiliation  

Assessment of CMV-specific T cell immunity might be a useful tool in predicting CMV infection after solid organ transplantation. We have investigated CD4 and CD8 T-cell responses to CMV pp65 and IE-1 antigens in a prospective study of 28 CMV-seropositive kidney transplant recipients who were administered lymphocyte-depleting antibodies (Thymoglobulin®) as induction treatment and with universal prophylaxis for CMV infection. The response was analyzed by intracellular flow cytometry analysis of IFN-γ production in pretransplant samples and at 1, 6, 12 and 24 months post-transplant. Overall, only pretransplant CD4 T-cell responses to pp65 were significantly lower (p = .004) in patients with CMV replication post-transplant. ROC curve analysis showed that pre-transplant frequencies of pp65-specific CD4 + T cells below 0.10% could predict CMV infection with 75% sensitivity and 83.33% specificity (AUC: 0.847; 95% CI: 0.693-1.001; p = .0054) and seem to be mandatory for efficient control of CMV viral replication by the host immune system. In conclusion, the functional assessment of CMV-specific CD4 T-cell immunity pretransplant in seropositive patients may allow the identification of Thymoglobulin®-treated kidney transplant recipients at risk of developing CMV infection post-transplantation.

中文翻译:

pp65特异性CD4 T细胞应答的移植前评估确定了接受rATG治疗的CMV血清反应阳性的患者有迟发感染的风险。

评估CMV特异性T细胞免疫可能是预测实体器官移植后CMV感染的有用工具。在一项对28名CMV血清阳性肾移植受者的前瞻性研究中,我们研究了对CMV pp65和IE-1抗原的CD4和CD8 T细胞应答,这些受试者接受了消耗淋巴细胞的抗体(Thymoglobulin®)的诱导治疗并普遍预防CMV感染。通过细胞内流式细胞术分析移植前样品以及移植后1、6、12和24个月产生的IFN-γ来分析反应。总体而言,只有CMV复制的患者在移植后,对pp65的移植前CD4 T细胞应答显着降低(p = .004)。ROC曲线分析表明,pp65特异性CD4 + T细胞的移植前频率低于0。10%可以以75%的敏感性和83.33%的特异性(AUC:0.847; 95%CI:0.693-1.001; p = .0054)预测CMV感染,并且似乎对于宿主免疫系统有效控制CMV病毒复制是必不可少的。总之,血清反应阳性患者在移植前对CMV特异性CD4 T细胞免疫的功能评估可以鉴定经Thymoglobulin®治疗的肾移植受者,其在移植后有发生CMV感染的风险。
更新日期:2019-12-29
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