Background: CMV-specific T-cell responses are crucial to protection of transplant patients against CMV viremia and disease. While studies have centered on CMV cytotoxic T-cells, using interferon-Γ (IFN) as a surrogate, little is known about the relevance of other cytokines and chemokines for CMV cell-mediated immunity (CMI) and outcomes in solid organ transplant recipients.
Methods: We evaluated cytokine and chemokine expression in two independent cohorts of patients tested with a commercially available CMV-CMI assay. Resulting plasma from CMV peptide-stimulated/non-stimulated blood was subjected to ELISA and Luminex quantitation of cytokines/chemokines.
Results: In a cohort of CMV-viremic transplant patients (n=37) enrolled at the onset of CMV-viremia, the responses of 65 cytokines/chemokines to CMV peptide stimulation were characterized. Aside from the IFN response, the response of the chemokines CCL8 (based on ROC curve analysis, AUC 0.85 95% CI 0.72 0.98; p=0.003) and CXCL10 (AUC 0.84 95% CI 0.71 0.97; p=0.004) was also highly predictive of spontaneous clearance of viremia. A classifier built including all 65 cytokines/chemokines corroborated the relevance of IFN/CCL8/CXCL10 to the correct classification of patients according to their viremia outcomes with an average cross-validation accuracy of 80%. In a second cohort comprising only CMV D+/R- patients (n=55) tested at time of discontinuation of antiviral prophylaxis after transplant (i.e. not viremic at the time of the testing), CCL8/CXCL10 responses were significantly higher in patients who developed CMV-CMI IFN responses during antiviral prophylaxis (p=0.003 and p<0.001, respectively) in comparison to those who did not. Moreover, irrespective of the presence of viremia, the magnitude of CCL8/CXCL10 responses was also similar between patients with a positive IFN CMV-CMI from the two different cohorts.
Conclusions: In addition to interferon-Γ production by CMV-specific T-cells, chemokines produced by other cell types appear to be relevant to the antiviral response against CMV and may serve as surrogates of virus-specific cellular immune responses. In CMV-viremic transplant patients, robust responses of CCL8 and CXCL10 to CMV peptide stimulation of whole blood were predictive of spontaneous clearance of viremia.
Kumar, D.: Grant/Research Support, Roche. Humar, A.: Grant/Research Support, Roche.
To cite this abstract in AMA style:Lisboa L, Egli A, O'Shea D, Prabhakaran S, Roth V, Husain S, Kumar D, Humar A. Chemokine Responses as Surrogates of CMV Cell-Mediated Immunity and Predictors of Outcomes in Transplant Recipients [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/chemokine-responses-as-surrogates-of-cmv-cell-mediated-immunity-and-predictors-of-outcomes-in-transplant-recipients/. Accessed May 7, 2021.
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