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Acquisition of cytomegalovirus specific immune response during pre-emptive therapy protects high-risk solid organ transplant patients from infection

Abstract number: O243

BenMarzouk-Hidalgo O., Cisneros J., Cordero E., Martin-Peña A., Sanchez B., Gomez-Bravo M., Gentil A., Lage E., Perez-Romero P.

Objectives: The objective of this study is to determine whether the activation of a cytomegalovirus (CMV)-specific T cell-mediated response during pre-emptive therapy controls further replication episodes without valganciclovir administration in solid organ transplant (SOT) patients at high risk for CMV infection.

Methods: SOT recipients at high risk for CMV infection, those that are seronegative and receive a seropositive graft, were followed for 18 months after transplantation. CMV viral loads (VL) were determined by real-time PCR, and the CMV-specific immune response was characterized by flow cytometry by the detection of CD4+, CD8+ and CD3+ T cells expressing CD69 and secreting IFN-g and IL-2. Preemptive treatment was administered when VL reached 1,000 copies/ml. Once a CMV-specific immune response was detected no treatment was administered and patients were closely monitored.

Results: Eleven patients with a median age of 53 years were included. Between 2 and 7 weeks after transplantation, all patients experienced CMV replication episodes that ranged from 787 to 1,432,217 copies/ml. All of them were resolved after administration of valganciclovir. Between weeks 10 and 20 post-transplantation a CMV-specific immune response was detected in all patients. After this, 33 replication episodes were detected, 32 of which (97%) were controled by the host immune system without the administration of treatment (VL ranging from 10 to 31,317 copies/ml). Furthermore, although the number of positive PCR results was similar before and after the acquisition of immunity, VL levels were significantly lower (p = 0.017) after immunity than before with median values of 1,696 copies/ml and 20,110 copies/ml, respectively. From week 39 to week 51 all replication episodes were 1,000 copies/ml and no new replication episodes were detected after week 51.

Analysis of the immune response demonstrated that IL-2 was secreted from CD4+ T cells significantly earlier than IFN-g (6 vs 8.5 weeks post-transplant; p = 0.001). Aditionally, IFN-g was secreted from CD4+ T cells significantly earlier than from CD8+ T cells (9 vs 12 weeks post-transplant; p = 0.005).

Conclusion: Pre-emptive therapy promotes the acquisition of an early immune response after transplantation in SOT patients at high risk for CMV infection. We demonstrate that the immune response elicited during pre-emptive therapy confers immunity to later CMV replication events.

Session Details

Date: 10/04/2010
Time: 00:00-00:00
Session name: Abstracts 20th European Congress of Clinical Microbiology and Infectious Diseases
Subject:
Location: Vienna, Austria, 10 - 13 April 2010
Presentation type:
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