Type I Interferon in Children with Viral or Bacterial Infections.


Journal

Clinical chemistry
ISSN: 1530-8561
Titre abrégé: Clin Chem
Pays: England
ID NLM: 9421549

Informations de publication

Date de publication:
01 06 2020
Historique:
received: 07 02 2020
accepted: 18 03 2020
pubmed: 3 5 2020
medline: 31 3 2021
entrez: 3 5 2020
Statut: ppublish

Résumé

Fever is one of the leading causes of consultation in the pediatric emergency department for patients under the age of 3 years. Distinguishing between bacterial and viral infections etiologies in febrile patients remains challenging. We hypothesized that specific host biomarkers for viral infections, such as type I-interferon (IFN), could help clinicians' decisions and limit antibiotic overuse. Paxgene tubes and serum were collected from febrile children (n = 101), age from 7 days to 36 months, with proven viral or bacterial infections, being treated at pediatric emergency departments in France. We assessed the performance of an IFN signature, which was based on quantification of expression of IFN-stimulated genes using the Nanostring® technology and plasma IFN-α quantified by digital ELISA technology. Serum concentrations of IFN-α were below the quantification threshold (30 fg/mL) for 2% (1/46) of children with proven viral infections and for 71% (39/55) of children with bacterial infections (P < 0.001). IFN-α concentrations and IFN score were significantly higher in viral compared to bacterial infection (P < 0.001). There was a strong correlation between serum IFN-α concentrations and IFN score (p-pearson = 0.83). Both serum IFN-α concentration and IFN score robustly discriminated (Area Under the Curve >0.91 for both) between viral and bacterial infection in febrile children, compared to C-reactive protein (0.83). IFN-α is increased in blood of febrile infants with viral infections. The discriminative performance of IFN-α femtomolar concentrations as well as blood transcriptional signatures could show a diagnostic benefit and potentially limit antibiotic overuse. clinicaltrials.gov (NCT03163628).

Sections du résumé

BACKGROUND
Fever is one of the leading causes of consultation in the pediatric emergency department for patients under the age of 3 years. Distinguishing between bacterial and viral infections etiologies in febrile patients remains challenging. We hypothesized that specific host biomarkers for viral infections, such as type I-interferon (IFN), could help clinicians' decisions and limit antibiotic overuse.
METHODS
Paxgene tubes and serum were collected from febrile children (n = 101), age from 7 days to 36 months, with proven viral or bacterial infections, being treated at pediatric emergency departments in France. We assessed the performance of an IFN signature, which was based on quantification of expression of IFN-stimulated genes using the Nanostring® technology and plasma IFN-α quantified by digital ELISA technology.
RESULTS
Serum concentrations of IFN-α were below the quantification threshold (30 fg/mL) for 2% (1/46) of children with proven viral infections and for 71% (39/55) of children with bacterial infections (P < 0.001). IFN-α concentrations and IFN score were significantly higher in viral compared to bacterial infection (P < 0.001). There was a strong correlation between serum IFN-α concentrations and IFN score (p-pearson = 0.83). Both serum IFN-α concentration and IFN score robustly discriminated (Area Under the Curve >0.91 for both) between viral and bacterial infection in febrile children, compared to C-reactive protein (0.83).
CONCLUSIONS
IFN-α is increased in blood of febrile infants with viral infections. The discriminative performance of IFN-α femtomolar concentrations as well as blood transcriptional signatures could show a diagnostic benefit and potentially limit antibiotic overuse.
CLINICAL TRIALS REGISTRATION
clinicaltrials.gov (NCT03163628).

Identifiants

pubmed: 32359149
pii: 5828219
doi: 10.1093/clinchem/hvaa089
doi:

Substances chimiques

Biomarkers 0
Interferon Type I 0

Banques de données

ClinicalTrials.gov
['NCT03163628']

Types de publication

Journal Article Multicenter Study Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

802-808

Investigateurs

Marine Mommert (M)
Audrey Guichard (A)
François Bartolo (F)
Laurence Generenaz (L)
Alexandre Pachot (A)
Claire Capella (C)
Laure Hees (L)
Ellia Mezgueldi (E)
Chadia Toumi (C)
Coralie Bouchiat-Sarabi (C)
Jean-Sebastien Casalegno (JS)
Aurelie Portefaix (A)
Romain Deshayes de Cambronne (RD)
Magali Perret (M)

Informations de copyright

© American Association for Clinical Chemistry 2020.

Auteurs

Sophie Trouillet-Assant (S)

Joint Research Unit Hospices Civils de Lyon-bioMérieux, Hospices Civils de Lyon, Lyon Sud Hospital, Pierre-Bénite, France.
Virologie et Pathologie Humaine - Virpath Team, Centre International de Recherche en Infectiologie (CIRI), INSERM U1111, CNRS UMR5308, ENS Lyon, Claude Bernard Lyon University, Lyon, France.

Sébastien Viel (S)

Immunoly Laboratory, Hospices Civils de Lyon, Lyon Sud Hospital, Pierre-Bénite, France.
Immunité innée dans les maladies infectieuses et autoimmunes team, Centre International de Recherche en Infectiologie (CIRI), INSERM U1111, CNRS UMR5308, ENS Lyon, Claude Bernard Lyon University, Lyon, France.
National Referee Centre for Rheumatic and AutoImmune and Systemic diseases in childrEn (RAISE), Lyon, France.

Antoine Ouziel (A)

Pediatric Emergency Unit, Hôpital Femme Mère Enfants, Hospices Civils of Lyon, Lyon, France.

Lucille Boisselier (L)

Joint Research Unit Hospices Civils de Lyon-bioMérieux, Hospices Civils de Lyon, Lyon Sud Hospital, Pierre-Bénite, France.

Philippe Rebaud (P)

Pediatric Emergency Unit, Hôpital Nord-Ouest, CH de Villefranche-sur-Saône, Gleizé, France.

Romain Basmaci (R)

Pediatric Emergency Unit, AP-HP, Louis-Mourier Hospital, Colombes, France.
Paris University, INSERM, Infection, Antimicrobiens, Modélisation, Evolution (IAME), Paris, France.

Nina Droz (N)

Pediatric Emergency Unit, AP-HP, Louis-Mourier Hospital, Colombes, France.

Alexandre Belot (A)

Immunité innée dans les maladies infectieuses et autoimmunes team, Centre International de Recherche en Infectiologie (CIRI), INSERM U1111, CNRS UMR5308, ENS Lyon, Claude Bernard Lyon University, Lyon, France.
National Referee Centre for Rheumatic and AutoImmune and Systemic diseases in childrEn (RAISE), Lyon, France.
Pediatric Nephrology, Rheumatology, Dermatology Unit, Hospices Civils de Lyon, Lyon, France.

Sylvie Pons (S)

Joint Research Unit Hospices Civils de Lyon-bioMérieux, Hospices Civils de Lyon, Lyon Sud Hospital, Pierre-Bénite, France.

Karen Brengel-Pesce (K)

Joint Research Unit Hospices Civils de Lyon-bioMérieux, Hospices Civils de Lyon, Lyon Sud Hospital, Pierre-Bénite, France.

Yves Gillet (Y)

Pediatric Emergency Unit, Hôpital Femme Mère Enfants, Hospices Civils of Lyon, Lyon, France.

Etienne Javouhey (E)

Pediatric Emergency Unit, Hôpital Femme Mère Enfants, Hospices Civils of Lyon, Lyon, France.
EA7426: Pathophysiology of Injury-Induced Immunosuppression, University of Lyon, Lyon, France.

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