Diagnostic utility of human cytomegalovirus-specific T-cell response monitoring in predicting viremia in pediatric allogeneic stem-cell transplant patients.
BACKGROUND
Several studies proved that virus-specific T-cells play a pivotal role in controlling cytomegalovirus (CMV) infection in adult allogeneic hematopoietic stem-cell transplant (HSCT) patients. Fewer data are available in pediatric HSCT settings, when immature and inexperienced immune system may affect antiviral immune reconstitution.


METHODS
We analyzed prospectively the CMV-specific T-cell reconstitution in a cohort of 31 pediatric allogeneic HSCT recipients at 30, 60, 90, 120, 180, and 360 days after HSCT.


RESULTS
Depending on donor-recipient CMV serostatus, we observed distinct patterns and kinetics of CMV-specific T-cell immune reconstitution: during the early time-points, patients displayed a severe reduction in CMV-specific T-cell recovery in both CMV seropositive donor (D+) group and CMV seronegative donor (D-) on CMV seropositive recipients (R+). From day 90 onward, statistical significant differences in the profile of T-cell immune reconstitution emerged between D+ and D-. The pattern of immune reconstitution was characterized by heterogeneous kinetics and efficiencies: we report cases of: (1) spontaneous antiviral T-cell recovery with no previous viremia, (2) immune T-cell recovery anticipated by CMV viremia, and (3) no T-cell immune reconstitution despite previous viremia episodes.


CONCLUSIONS
Given the heterogeneous scenarios of antiviral T-cell immune recovery in pediatric allogeneic HSCT, we conclude that the evaluation of the antiviral immune reconstitution is a promising and appealing system for identifying patients at higher risk of CMV infection. The use of interferon-γ ELISPOT test is a valid tool for immunological monitoring and predicting CMV viremia in pediatric HSCT.
Department of Histology, Microbiology and Medical Biotechnology, University of Padua, Padova, Italy. davide.abate@unipd.it
Davide
D
Abate
Simone
S
Cesaro
Simona
S
Cofano
Marta
M
Fiscon
Alda
A
Saldan
Stefania
S
Varotto
Carlo
C
Mengoli
Marta
M
Pillon
Elisabetta
E
Calore
Maria Angela
MA
Biasolo
Riccardo
R
Cusinato
Luisa
L
Barzon
Chiara
C
Messina
Modesto
M
Carli
Giorgio
G
Palù
D000293:Adolescent; D000367:Age Factors; D002648:Child; D002675:Child, Preschool; D003587:Cytomegalovirus / Q000276:immunology* / Q000472:pathogenicity; D003586:Cytomegalovirus Infections / Q000175:diagnosis* / Q000276:immunology / Q000401:mortality / Q000821:virology; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000401:mortality; D006801:Humans; D007111:Immunity, Cellular; D007223:Infant; D007558:Italy; D053208:Kaplan-Meier Estimate; D008297:Male; D015166:Monitoring, Immunologic / Q000379:methods*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D013997:Time Factors; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014766:Viremia / Q000276:immunology