Mees Soeren Torge, Kebschull Linus, Mardin Wolf Arif, Senninger Norbert, Suwelack Barbara, Wolters Heiner, Haier Joerg
1 Department of General and Visceral Surgery, University Hospital Muenster , Muenster, Germany .
Surg Infect (Larchmt). 2014 Jun;15(3):274-82. doi: 10.1089/sur.2013.083. Epub 2014 May 6.
The early diagnosis of viral reactivation after kidney transplantation (KTX) is an unsolved problem. Survey of virus-specific T-cell responses may identify patients at risk for viral reactivation. We therefore quantified virus-specific CD8+ T-cells to evaluate their potential predictive value for viral reactivation and infection in KTX patients.
We quantified the virus-specific responses of CD8+ T-cells for CMV, EBV, HPV and HHV in 23 patients undergoing KTX for 6 mo after transplantation. We enumerated T-cells for 36 virus-specific binding peptides and five different human leukocyte antigen (HLA) alleles through the binding of Class I iTAg major histocompatibility complex (MHC) tetramers. The patients' pre-operative serologic status for CMV and CMV-specific CD8+ T-cell numbers were correlated with one another (p=0.0046).
Three patients had clinical CMV disease and all three remained or became CMV-tetramer-positive for at least one HLA allele during follow-up. Three of the four patients with viral infections caused by or reactivations of viruses other than CMV were initially negative for CMV-specific CD8+ T-cells but became CMV-positive. Most of the patients who were initially CMV-tetramer positive also had tetramer-positive T-cells specific for Epstein-Barr virus (EBV); human papillomavirus (HPV)-6b, -11, -16, or -18; or human herpesvirus (HHV)-8. All of the patients who developed viral disease other than that caused by CMV remained or became positive for at least one binding peptide that was specific for a virus not directly related to the clinical features of a viral disease.
Patients who were positive for any virus had a significantly greater risk of developing complications of viral disease during the 6-mo follow-up period in the study (p=0.026), suggesting a general susceptibility to viral reactivation. The evaluation of virus-specific CD8+ T-cells may prospectively help to identify patients at risk for viral reactivation after KTX.
肾移植（KTX）后病毒再激活的早期诊断是一个尚未解决的问题。对病毒特异性T细胞反应的检测可能会识别出有病毒再激活风险的患者。因此，我们对病毒特异性CD8 + T细胞进行定量，以评估其对KTX患者病毒再激活和感染的潜在预测价值。
我们对23例接受KTX的患者在移植后6个月内针对巨细胞病毒（CMV）、EB病毒（EBV）、人乳头瘤病毒（HPV）和人疱疹病毒（HHV）的CD8 + T细胞的病毒特异性反应进行了定量。我们通过I类iTAg主要组织相容性复合体（MHC）四聚体的结合，对36种病毒特异性结合肽和5种不同的人类白细胞抗原（HLA）等位基因的T细胞进行了计数。患者术前CMV血清学状态与CMV特异性CD8 + T细胞数量相互关联（p = 0.0046）。
3例患者出现临床CMV疾病，且在随访期间，所有3例患者至少对一种HLA等位基因保持CMV四聚体阳性或变为阳性。4例由CMV以外的病毒引起病毒感染或病毒再激活的患者中，有3例最初CMV特异性CD8 + T细胞呈阴性，但后来变为阳性。大多数最初CMV四聚体阳性的患者也有针对EB病毒（EBV）、人乳头瘤病毒（HPV）-6b、-11、-16或-18、或人疱疹病毒（HHV）-8的四聚体阳性T细胞。所有发生CMV以外病毒疾病的患者对至少一种与病毒疾病临床特征无直接关系的病毒特异性结合肽保持阳性或变为阳性。
在本研究的6个月随访期内，任何病毒呈阳性的患者发生病毒疾病并发症的风险显著更高（p = 0.026），这表明对病毒再激活普遍易感。对病毒特异性CD8 + T细胞的评估可能有助于前瞻性地识别KTX后有病毒再激活风险的患者。
