6533b838fe1ef96bd12a501c

RESEARCH PRODUCT

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

Jose B NietoJuan C. Hernández-boludaR De La CámaraNuria TormoN López-aldeguerI BenetAna García-noblejasCarlos SolanoJavier María García LópezMaría ÁNgeles ClariM J RemigiaDavid NavarroConcepción Gimeno

subject

AdultCD4-Positive T-LymphocytesMaleGanciclovirAdolescentvirusesCongenital cytomegalovirus infectionCytomegalovirusCD8-Positive T-LymphocytesOpportunistic Infectionsmedicine.disease_causeHerpesviridaeImmediate-Early ProteinsViral Matrix ProteinsInterferon-gammaYoung AdultAntigenBetaherpesvirinaeDrug Resistance ViralmedicineHumansTransplantation HomologousAntigens ViralGanciclovirAgedTransplantationbiologybusiness.industryHematopoietic Stem Cell Transplantationvirus diseasesHematologyMiddle AgedPhosphoproteinsbiology.organism_classificationmedicine.diseaseTransplantationsurgical procedures operativeCytomegalovirus InfectionsDNA ViralMutationImmunologyFemaleStem cellbusinessCD8medicine.drug

description

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=68) that were pre-emptively 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 IFNgamma CD8(+) T and IFNgamma CD4(+) 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 IFNgamma CD8(+) and CD4(+) T cells is associated with rising levels in antigenemia and DNAemia during pre-emptive therapy.

https://doi.org/10.1038/bmt.2009.172