title: Human cytomegalovirus-specific T-cell immune reconstitution in preemptively treated heart transplant recipients identifies subjects at critical risk for infection.
abstract: Human cytomegalovirus (CMV) infection represents a major threat for heart transplant recipients (HTXs). CMV-specific T cells effectively control virus infection, and thus, assessment of antiviral immune recovery may have clinical utility in identifying HTXs at risk of infection. In this study, 10 CMV-seropositive (R(+)) pretransplant patients and 48 preemptively treated R(+) HTXs were examined before and after 100 days posttransplant. Preemptive treatment is supposed to favor the immune recovery. CMV DNAemia and gamma interferon enzyme-linked immunosorbent spot (ELISPOT) assay were employed to assess the viremia and immune reconstitution. HTXs could be categorized into three groups characterized by high (>100), medium (50 to 100), and low (<50) spot levels. Early-identified high responders efficiently controlled the infection and also maintained high immunity levels after 100 days after transplant. No episodes of grade ≥2R rejection occurred in the high responders. Midresponders were identified as a group with heterogeneous trends of immune reconstitution. Low responders were 41% and 21% of HTXs before and after 100 days posttransplant, respectively. Low responders were associated with a higher incidence of infection. The effect of viremia on immune recovery was investigated: a statistically significant inverse correlation between magnitude of viremia and immune recovery emerged; in particular, each 10-fold increase in viremia (>4 log(10) DNAemia/ml) was associated with a 36% decrease of the ELISPOT assay spot levels. All episodes of high viremia (>4 log(10) DNAemia/ml) occurred from 1 to 60 days after transplant. Thus, the concomitant evaluation of viremia and CMV immune reconstitution has clinical utility in identifying HTXs at risk of infection and may represent a helpful guide in making therapeutic choices.
authors.affiliation: Department of Molecular Medicine, Padua General Hospital, University of Padua School of Medicine, Padua, Italy. davide.abate@unipd.it
authors.forename: Davide
authors.initials: D
authors.lastname: Abate
authors.forename: Marta
authors.initials: M
authors.lastname: Fiscon
authors.forename: Alda
authors.initials: A
authors.lastname: Saldan
authors.forename: Simona
authors.initials: S
authors.lastname: Cofano
authors.forename: Carlo
authors.initials: C
authors.lastname: Mengoli
authors.forename: Dino
authors.initials: D
authors.lastname: Sgarabotto
authors.forename: Chiara
authors.initials: C
authors.lastname: d'Agostino
authors.forename: Luisa
authors.initials: L
authors.lastname: Barzon
authors.forename: Riccardo
authors.initials: R
authors.lastname: Cusinato
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Toscano
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Feltrin
authors.forename: Antonio
authors.initials: A
authors.lastname: Gambino
authors.forename: Gino
authors.initials: G
authors.lastname: Gerosa
authors.forename: Giorgio
authors.initials: G
authors.lastname: Palù
mesh_terms: D000328:Adult; D000368:Aged; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000453:epidemiology* / Q000276:immunology / Q000517:prevention & control*; D004279:DNA, Viral / Q000097:blood; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D006331:Heart Diseases / Q000601:surgery; D006801:Humans; D016867:Immunocompromised Host; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016377:Organ Transplantation / Q000009:adverse effects; D018570:Risk Assessment; D013601:T-Lymphocytes / Q000276:immunology*; D019562:Viral Load; D014766:Viremia / Q000175:diagnosis
chemical_list: D004279:DNA, Viral; D007371:Interferon-gamma