Lack of prompt expansion of cytomegalovirus pp65 and IE-1-specific IFNγ CD8+ and CD4+ T cells is associated with rising levels of pp65 antigenemia and DNAemia during pre-emptive therapy in allogeneic hematopoietic stem cell transplant recipients

Abstract

Rising levels of cytomegalovirus (CMV) DNAemia and/or pp65 antigenemia have been observed during pre-emptive ganciclovir therapy in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-SCT). We assessed the incidence of this event in our series, and investigated whether its occurrence was associated with an impairment in the CMV-specific T-cell response. A total of 36 allo-SCT recipients experienced one or more episodes of active CMV infection (n ¼ 68) that were preemptively treated with val(ganciclovir). Rising levels of antigenemia and DNAemia, and an isolated increase in antigenemia, were observed in 39.7 and 2.9% of all episodes, respectively. Receipt of corticosteroids was associated with rising levels of antigenemia and DNAemia. Median increases of 12-and 6.8-fold of IFNc CD8 þ T and IFNc CD4 þ T cells, respectively, were observed at a median of 16.5 days after initiation of therapy in episodes with decreasing levels in antigenemia and DNAemia. In contrast, the numbers of both T-cell subsets at a median of 13.5 days after initiation of therapy did not differ significantly from those of pre-treatment samples in episodes with rising levels of antigenemia and DNAemia. Lack of prompt expansion of CMV pp65 and IE-1-specific IFNc CD8 þ and CD4 þ T cells is associated with rising levels in antigenemia and DNAemia during pre-emptive therapy.

Role of cytomegalovirus (CMV)-specific polyfunctional CD8+ T-cells and antibodies neutralizing virus epithelial infection in the control of CMV infection in an allogeneic stem-cell transplantation setting

“…In contrast, the levels of CMV (AD169)-specific IgGs measured by CLIA were not predictive of the occurrence of CMV DNAemia. In our opinion, if AbNEIs displayed a relevant role in conferring protection against CMV viraemia, the opposite phenomenon would be expected to occur, as has been shown for CMV-specific functional T-cells Tormo et al, 2010aTormo et al, , b, 2011. Several non-mutually exclusive explanations may account for this finding.…”

“…Monitoring of plasma CMV DNAemia was performed once a week using a real-time PCR assay (CMV real-time PCR or Abbott RealTime CMV; Abbott Molecular) (Clari et al, 2013;Giménez et al, 2014;Gimeno et al, 2008). Patients were treated pre-emptively with antivirals as described previously Tormo et al, 2010aTormo et al, , b, 2011. CMV DNAemia (active CMV infection) was defined as the detection of any level of CMV DNA in plasma.…”

Pre-emptive antiviral therapy for active CMV infection in adult allo-SCT patients guided by plasma CMV DNAemia quantitation using a real-time PCR assay: clinical experience at a single center

“…Type B episodes were those in which rising levels of CMV DNAemia (increases Xfive-fold) were demonstrated after the implementation of antiviral therapy. 8 As shown in Table 1, the demographic and clinical characteristics of patients in both groups were not significantly different. As shown in Table 2, the incidence rate of episodes of active CMV infection and that of recurrent episodes occurred more frequently in patients in group I than in those in group II, though statistical significance was not reached.…”

Immunotherapy for opportunistic infections: Current status and future perspectives

“…[34][35][36] Lack of T cell immunity against CMV is associated with an increased risk of late onset/recurrent CMV antigenemia and CMV disease. 21,[23][24][25][26][27][28][29] In EBV and ADV infections, importance of T cell immunity against was also reported. [37][38][39] Therefore, if T cell immunity is found to be insufficient in patients with viral reactivation, adoptive immunotherapy to enhance T cell reconstitution could be an option to consider in order to treat or prevent the development of endorgan disease (Fig.…”

“…In terms of viral infections, it is well established that T cells play an important role. [21][22][23][24][25][26][27][28][29][30] In terms of mold infections, innate immunity alone was considered important historically in the control of mold infections. However, recent studies found that adaptive immunity, in particular Th1 cells, was relevant in the control of aspergillus infections.…”