Immune reconstitution and clearance of human adenovirus viremia in pediatric stem-cell recipients.
BACKGROUND
Human adenovirus (HAdV) infections are increasingly frequent complications of allogeneic stem-cell transplantation (SCT), especially in children. Only a few data on the correlation between immune recovery and the course of HAdV infection are available, and data on HAdV-specific responses are lacking.


METHODS
In a prospective study, we determined the correlation between the HAdV DNA load in plasma and lymphocyte reconstitution in 48 children after allogeneic SCT. Additionally, HAdV-specific humoral and cellular immune responses were investigated.


RESULTS
HAdV infection occurred in 21 patients (44%), and, in 6 of these patients, the infection progressed to viremia, as demonstrated by the presence of HAdV DNA in plasma. Low lymphocyte counts at the onset of infection were predictive of HAdV viremia. Survival of patients with HAdV viremia was associated with an increase in lymphocyte counts during the first weeks after infection. In these patients, HAdV-specific CD4+ T cell responses, as well as increases in titers of neutralizing antibody, were detected after clearance of HAdV DNA from plasma.


CONCLUSIONS
Lymphocyte reconstitution appears to play a crucial role in clearance of HAdV viremia and survival of the host, warranting further development of therapeutic interventions aimed at improving immune recovery.
Heemskerk
Bianca
B
Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands.
Lankester
Arjan C
AC
van Vreeswijk
Tamara
T
Beersma
Matthias F C
MF
Claas
Eric C J
EC
Veltrop-Duits
Louise A
LA
Kroes
Aloys C M
AC
Vossen
Jaak M J J
JM
Schilham
Marco W
MW
van Tol
Maarten J D
MJ
D000258:Adenovirus Infections, Human / Q000276:immunology* / Q000821:virology*; D000260:Adenoviruses, Human / Q000276:immunology* / Q000302:isolation & purification*; D000293:Adolescent; D000914:Antibodies, Viral / Q000097:blood*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D004279:DNA, Viral / Q000097:blood; D005260:Female; D006801:Humans; D007223:Infant; D018655:Lymphocyte Count; D008214:Lymphocytes / Q000276:immunology*; D008297:Male; D009500:Neutralization Tests; D012189:Retrospective Studies; D033581:Stem Cell Transplantation; D013534:Survival; D019562:Viral Load; D014766:Viremia
D000914:Antibodies, Viral; D004279:DNA, Viral