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Specific Immunity to Cytomegalovirus in Pediatric Cardiac Transplantation

Jacobsen, MC; Manunta, MDI; Pincott, ES; Fenton, M; Simpson, GL; Klein, NJ; Burch, M; (2018) Specific Immunity to Cytomegalovirus in Pediatric Cardiac Transplantation. Transplantation , 102 (9) pp. 1569-1575. 10.1097/TP.0000000000002157. Green open access

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Abstract

BACKGROUND: Cytomegalovirus (CMV) infection is implicated in endothelial dysfunction and graft damage after pediatric heart transplantation. CMV specific immune responses are thought to be necessary for CMV viral control but there is little data in pediatric heart transplantation. METHODS: We studied 28 consecutive pediatric heart transplant recipients for 1-year posttransplant. CMV-specific T cells expressing IFN-γ, TNF-α and IL-2 in response to ex-vivo stimulation with CMV lysates or peptides were measured. Circulating cytokines were measured in plasma. Generalised Additive Models were applied to the data to model changes of cell population dynamics over time. RESULTS: CMV-specific T cell mediated responses were impaired in the first 8 weeks posttransplant. During this period, 25% of patients had CMV viremia, of which those with viral loads ≥10,000 CMV DNA copies/mL were given ganciclovir. In this group, the frequency of CD4+ and CD8+ T cells producing IFN-γ and the CD8+CD57+GB+ T cell population increased at 12-24 weeks and remained elevated for the duration of the study. CONCLUSIONS: We have shown that CMV viremia is associated with CMV specific immune responses and increased CD8+CD57+GB+ cells at 1-year posttransplant, however early responses were not predictive of impending CMV viremia. It remains to be seen if the early CMV immune response detected is associated with endothelial and allograft damage, in light of previous studies demonstrating increased vasculopathy in pediatric patients with CMV viremia.

Type: Article
Title: Specific Immunity to Cytomegalovirus in Pediatric Cardiac Transplantation
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1097/TP.0000000000002157
Publisher version: http://dx.doi.org/10.1097/TP.0000000000002157
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Cytomegalovirus, inflammation, cytokines, endothelial dysfunction, coronary artery vasculopathy
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10052055
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