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Thymus activity measured by T-cell receptor excision circles in patients with different severities of respiratory syncytial virus infection

BACKGROUND: 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...

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Autores principales: Gul, Kiran Aftab, Sonerud, Tonje, Fjærli, Hans O., Nakstad, Britt, Abrahamsen, Tore Gunnar, Inchley, Christopher S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5217228/
https://www.ncbi.nlm.nih.gov/pubmed/28056841
http://dx.doi.org/10.1186/s12879-016-2148-0
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author Gul, Kiran Aftab
Sonerud, Tonje
Fjærli, Hans O.
Nakstad, Britt
Abrahamsen, Tore Gunnar
Inchley, Christopher S.
author_facet Gul, Kiran Aftab
Sonerud, Tonje
Fjærli, Hans O.
Nakstad, Britt
Abrahamsen, Tore Gunnar
Inchley, Christopher S.
author_sort Gul, Kiran Aftab
collection PubMed
description BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
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spelling pubmed-52172282017-01-09 Thymus activity measured by T-cell receptor excision circles in patients with different severities of respiratory syncytial virus infection Gul, Kiran Aftab Sonerud, Tonje Fjærli, Hans O. Nakstad, Britt Abrahamsen, Tore Gunnar Inchley, Christopher S. BMC Infect Dis Research Article BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. BioMed Central 2017-01-05 /pmc/articles/PMC5217228/ /pubmed/28056841 http://dx.doi.org/10.1186/s12879-016-2148-0 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Gul, Kiran Aftab
Sonerud, Tonje
Fjærli, Hans O.
Nakstad, Britt
Abrahamsen, Tore Gunnar
Inchley, Christopher S.
Thymus activity measured by T-cell receptor excision circles in patients with different severities of respiratory syncytial virus infection
title Thymus activity measured by T-cell receptor excision circles in patients with different severities of respiratory syncytial virus infection
title_full Thymus activity measured by T-cell receptor excision circles in patients with different severities of respiratory syncytial virus infection
title_fullStr Thymus activity measured by T-cell receptor excision circles in patients with different severities of respiratory syncytial virus infection
title_full_unstemmed Thymus activity measured by T-cell receptor excision circles in patients with different severities of respiratory syncytial virus infection
title_short Thymus activity measured by T-cell receptor excision circles in patients with different severities of respiratory syncytial virus infection
title_sort thymus activity measured by t-cell receptor excision circles in patients with different severities of respiratory syncytial virus infection
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5217228/
https://www.ncbi.nlm.nih.gov/pubmed/28056841
http://dx.doi.org/10.1186/s12879-016-2148-0
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