Preformed Frequencies of Cytomegalovirus (CMV)-Specific Memory T and B Cells Identify Protected CMV-Sensitized Individuals Among Seronegative Kidney Transplant Recipients
Preformed Frequencies of Cytomegalovirus (CMV)-Specific Memory T and B Cells Identify Protected CMV-Sensitized Individuals Among Seronegative Kidney Transplant Recipients
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DOI：
10.1093/cid/ciu589
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发表时间：
2014-12-01
影响因子：
11.8
通讯作者：
Bestard, Oriol
中科院分区：
文献类型：
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作者：
Lucia, Marc;Crespo, Elena;Bestard, Oriol
背景资料。巨细胞病毒(CMV)感染仍是肾移植术后的主要并发症。基线CMV风险通常由预先形成的CMV特异性免疫球蛋白(Ig)G抗体的血清学存在来确定，即使T细胞对主要病毒抗原的反应在控制病毒复制时是至关重要的。一些接受免疫球蛋白抗体阳性的同种异体移植的免疫球蛋白抗体阴性的患者，即使没有接受预防，也不会发展成巨细胞病毒感染。我们假设，使用B细胞和T细胞酶联免疫斑点试验对移植前CMV特异性免疫致敏作用进行更准确的评估可能会更准确地识别CMV致敏个体，而不考虑CMV特异性抗体滴度的血清学证据。我们比较了43例CMV血清抗体阴性(sr(-))和86例CMV抗体阳性(sr(+))肾移植受者体内预先形成的CMV特异性记忆B细胞和T细胞的存在情况。对两组的临床结果进行评估。所有sr+患者都表现出广泛的CMV特异性记忆T细胞和B细胞反应。30%的sr患者也明显检测到高记忆性T和B细胞频率，而那些具有高CMV特异性T细胞频率的患者在预防性治疗后晚期CMV感染的发生率显著降低。受试者工作特征曲线对CMV病毒血症和疾病的预测分析显示受试者工作特征曲线下方有较高的区域(>；0.8)，具有较高的灵敏度和阴性预测值。肾移植前在sr受体中评估CMV特异性记忆T和B细胞反应可能有助于更准确地识别免疫个体，最终处于较低的CMV感染风险。
Background. Cytomegalovirus (CMV) infection remains a major complication after kidney transplantation. Baseline CMV risk is typically determined by the serological presence of preformed CMV-specific immunoglobulin (Ig) G antibodies, even though T-cell responses to major viral antigens are crucial when controlling viral replication. Some IgG-seronegative patients who receive an IgG-seropositive allograft do not develop CMV infection despite not receiving prophylaxis. We hypothesized that a more precise evaluation of pretransplant CMV-specific immune-sensitization using the B and T-cell enzyme-linked immunospot assays may identify CMV-sensitized individuals more accurately, regardless of serological evidence of CMV-specific IgG titers.Methods. We compared the presence of preformed CMV-specific memory B and T cells in kidney transplant recipients between 43 CMV IgG-seronegative (sR(-)) and 86 CMV IgG-seropositive (sR(+)) patients. Clinical outcome was evaluated in both groups.Results. All sR+ patients showed a wide range of CMV-specific memory T-and B-cell responses. High memory T-and B-cell frequencies were also clearly detected in 30% of sR-patients, and those with high CMV-specific T-cell frequencies had a significantly lower incidence of late CMV infection after prophylactic therapy. Receiver operating characteristic curve analysis for predicting CMV viremia and disease showed a high area under the receiver operating characteristic curve (>0.8), which translated into a high sensitivity and negative predictive value of the test.Conclusions. Assessment of CMV-specific memory T-and B-cell responses before kidney transplantation among sR-recipients may help identify immunized individuals more precisely, being ultimately at lower risk for CMV infection.