title: Thymus activity measured by T-cell receptor excision circles in patients with different severities of respiratory syncytial virus infection.
abstract: Respiratory syncytial virus (RSV) infection is an important cause of hospitalization in previously healthy infants. Immunological mechanisms predisposing infants to severe disease are poorly understood. Early biomarkers for disease severity may assist clinical decisions. We investigated T-cell receptor excision circles (TREC), episomal DNA made during thymic T-cell receptor rearrangement, and a marker for thymus activity, both during disease and in neonatal screening cards as a risk factor for RSV disease severity.
  
  
  
  One hundred thirteen patients hospitalized with RSV infection <12 months of age, grouped by disease severity, were available for this investigation, in which we conducted both a prospective and a case-control study. The prospective study included 47 RSV positive infants (mild n = 13, moderate n = 10, severe n = 24). TREC counts were determined by PCR of DNA extracted from EDTA-blood collected on hospitalization, and corrected for lymphocytes using ANCOVA. The case-control study included 85 newborns who later in infancy became RSV positive (mild n = 32, moderate n = 24, severe n = 29) and 47 newborns who never developed RSV disease as healthy controls included from health centres in the same catchment area. TRECs were measured using DNA extracted from dry blood spots from stored neonatal screening cards, followed by PCR. Student's T-test compared patients with controls, ANOVA compared disease severity groups.
  
  
  
  During RSV infection patients in the severe disease group had significantly lower (p = 0.017) TREC/200 μL blood compared to the other two disease groups, after correction for lymphocyte count. Newborn TREC levels, were significantly higher in RSV patients compared to controls (p < 0.0001). No significant differences in TREC copies at birth were found between disease severities.
  
  
  
  During acute RSV infection a lower number of TREC is found in the severe disease group. TREC has potential as an immunological marker for severe RSV infection. Higher neonatal TREC counts indicate that infants later presenting with severe RSV do not have reduced thymic activity at birth and probably no congenital T-cell defect.
authors.affiliation: Department of Pediatric Research, Women and Children's Division, Oslo University Hospital Rikshospitalet, Oslo, Norway. Kiran.aftab.gul@rr-research.no.|Department of National Newborn Screening, Women and Children's Division, Oslo University Hospital Rikshospitalet, Oslo, Norway. Kiran.aftab.gul@rr-research.no.|Clinic of Pediatric and Adolescent Medicine, Women and Children's Division, Oslo University Hospital Rikshospitalet, Oslo, Norway. Kiran.aftab.gul@rr-research.no.
authors.forename: Kiran Aftab
authors.initials: KA
authors.lastname: Gul
authors.affiliation: Department of Pediatric and Adolescent Medicine, Akershus University Hospital, Lørenskog, Norway.|Department of Clinical Molecular Biology and Laboratory Sciences (EpiGen), University of Oslo, Akershus University Hospital, Lørenskog, Norway.
authors.forename: Tonje
authors.initials: T
authors.lastname: Sonerud
authors.affiliation: Department of Pediatric and Adolescent Medicine, Akershus University Hospital, Lørenskog, Norway.
authors.forename: Hans O
authors.initials: HO
authors.lastname: Fjærli
authors.affiliation: Department of Pediatric and Adolescent Medicine, Akershus University Hospital, Lørenskog, Norway.|Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Britt
authors.initials: B
authors.lastname: Nakstad
authors.affiliation: Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|Clinic of Pediatric and Adolescent Medicine, Women and Children's Division, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors.forename: Tore Gunnar
authors.initials: TG
authors.lastname: Abrahamsen
authors.affiliation: Department of Pediatric and Adolescent Medicine, Akershus University Hospital, Lørenskog, Norway.|Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Inchley
mesh_terms: D016022:Case-Control Studies; D004247:DNA / Q000097:blood*; D059788:Dried Blood Spot Testing; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018655:Lymphocyte Count; D008297:Male; D011446:Prospective Studies; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D018357:Respiratory Syncytial Virus Infections / Q000209:etiology / Q000235:genetics* / Q000276:immunology; D013950:Thymus Gland / Q000821:virology*
chemical_list: D011948:Receptors, Antigen, T-Cell; D004247:DNA
keywords: Bronchiolitis; Children; Respiratory syncytial virus; T-cell receptor excision circles; Thymus