title: High titers of pre-existing adenovirus serotype-specific neutralizing antibodies in the host predict viral reactivation after allogeneic stem cell transplantation in children.
abstract: BACKGROUND
  Human adenovirus (HAdV) infections are frequent in children after allogeneic stem cell transplantation (SCT) and may become fatal. Whether these infections occur through reactivation of endogenous virus or transmission via the graft remains a matter of debate.
  
  
  METHODS
  In a cohort of 24 pediatric patients who received SCT, infections with 1 or more of 5 serotypes of HAdV (1, 2, 5, 6, and 31) were detected by culture. Neutralizing antibody (NAb) titers were measured in vitro by means of a virus neutralization assay.
  
  
  RESULTS
  In 11 patients the infection was restricted to 1 site as demonstrated by culture only, and in 13 patients the HAdV infection was disseminated because plasma samples contained HAdV DNA. The 5 most commonly encountered HAdV serotypes caused 35 infectious episodes after SCT. Serum titers of NAb against these 5 serotypes of HAdV were measured before and after transplantation. High titers of NAb against a certain serotype in the recipient prior to SCT, reflecting previous infection, appeared to predispose for infection with the same serotype after SCT. In only 1 case of 41 independent samples of graft material, a very low level of HAdV DNA was detected. Antibody responses after SCT were detected in 21 of 35 infectious episodes.
  
  
  CONCLUSIONS
  Together, these data suggest that adenoviral complications after SCT are caused by reactivation of endogenous persistent HAdV rather than by de novo infection from the donor or environment. This finding may offer a strategy of prophylactic treatment of high-risk patients before SCT to prevent infectious complications after allogeneic SCT.
authors.affiliation: Department of Pediatrics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Louise A
authors.initials: LA
authors.lastname: Veltrop-Duits
authors.forename: Tamara
authors.initials: T
authors.lastname: van Vreeswijk
authors.forename: Bianca
authors.initials: B
authors.lastname: Heemskerk
authors.forename: Joyphi C P
authors.initials: JC
authors.lastname: Thijssen
authors.forename: Ragad
authors.initials: R
authors.lastname: El Seady
authors.forename: Els M
authors.initials: EM
authors.lastname: Jol-van der Zijde
authors.forename: Eric C J
authors.initials: EC
authors.lastname: Claas
authors.forename: Arjan C
authors.initials: AC
authors.lastname: Lankester
authors.forename: Maarten J D
authors.initials: MJ
authors.lastname: van Tol
authors.forename: Marco W
authors.initials: MW
authors.lastname: Schilham
mesh_terms: D000256:Adenoviridae / Q000276:immunology*; D000257:Adenoviridae Infections / Q000453:epidemiology* / Q000209:etiology* / Q000276:immunology / Q000821:virology; D000293:Adolescent; D057134:Antibodies, Neutralizing / Q000097:blood*; D000914:Antibodies, Viral / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D016867:Immunocompromised Host; D007223:Infant; D008297:Male; D011379:Prognosis; D033581:Stem Cell Transplantation / Q000009:adverse effects*; D014775:Virus Activation
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral