title: Lack of prompt expansion of cytomegalovirus pp65 and IE-1-specific IFNgamma 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=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.
authors.affiliation: Microbiology Service, Hospital Clínico Universitario, Valencia, Spain.
authors.forename: N
authors.initials: N
authors.lastname: Tormo
authors.forename: C
authors.initials: C
authors.lastname: Solano
authors.forename: I
authors.initials: I
authors.lastname: Benet
authors.forename: M A
authors.initials: MA
authors.lastname: Clari
authors.forename: J
authors.initials: J
authors.lastname: Nieto
authors.forename: R
authors.initials: R
authors.lastname: de la Cámara
authors.forename: J
authors.initials: J
authors.lastname: López
authors.forename: N
authors.initials: N
authors.lastname: López-Aldeguer
authors.forename: J C
authors.initials: JC
authors.lastname: Hernández-Boluda
authors.forename: M J
authors.initials: MJ
authors.lastname: Remigia
authors.forename: A
authors.initials: A
authors.lastname: Garcia-Noblejas
authors.forename: C
authors.initials: C
authors.lastname: Gimeno
authors.forename: D
authors.initials: D
authors.lastname: Navarro
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000956:Antigens, Viral / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003587:Cytomegalovirus / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D003586:Cytomegalovirus Infections / Q000209:etiology* / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D004279:DNA, Viral / Q000097:blood; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D015774:Ganciclovir / Q000494:pharmacology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D017874:Immediate-Early Proteins / Q000097:blood; D007371:Interferon-gamma / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009894:Opportunistic Infections / Q000209:etiology / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D010750:Phosphoproteins / Q000097:blood; D014184:Transplantation, Homologous; D014763:Viral Matrix Proteins / Q000097:blood; D055815:Young Adult
chemical_list: D000956:Antigens, Viral; D004279:DNA, Viral; C088645:IE1 protein, cytomegalovirus; D017874:Immediate-Early Proteins; D010750:Phosphoproteins; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa; D007371:Interferon-gamma; D015774:Ganciclovir