Altered cytokine profiles in children with indeterminate quantiferon results and common infections - 01/07/15

Doi : 10.1016/j.jinf.2015.03.014

Mohamed Jeljeli ^a, Valérie Guérin-El Khourouj ^a, Agathe de Lauzanne ^b, Marine Armand ^a, Vibol Chhor ^c, Béatrice Pédron ^a, Stéphane Dauger ^d, Jérôme Viala ^e, Pierre Gressens ^f, Albert Faye ^b, Ghislaine Sterkers ^a,^⁎
^a Laboratory of Immunology, Robert-Debré Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Univ. Paris Diderot, Sorbonne Paris Cité, 75019 Paris, France
^b Department of Pediatric Infectious Disease, Robert-Debré Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Univ. Paris Diderot, Sorbonne Paris Cité, 75019 Paris, France
^c Department of Anesthesiology and Intensive Care Unit, European Georges Pompidou Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Univ. Paris Descartes, Sorbonne Paris Cité, 75015 Paris, France
^d Department of Pediatric Intensive Care Unit, Robert-Debré Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Univ. Paris Diderot, Sorbonne Paris Cité, 75019 Paris, France
^e Department of Pediatric Gastroenterology, Robert Debré Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Univ. Paris Diderot, Sorbonne Paris Cité, 75019 Paris, France
^f INSERM U1141, Robert-Debré Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Univ. Paris Diderot, Sorbonne Paris Cité, 75019 Paris, France

^∗Corresponding author. Hôpital Robert Debré – Laboratoire d'Immunologie, 48, Boulevard Sérurier, 75019 Paris, France. Tel.: +33 1 40 03 53 05; fax: +33 1 40 03 47 76.

Summary

Objectives

An increased rate of indeterminate quantiferon results (low IFN-γ release in the phytohemagglutinin-stimulated tube) has been reported in children with clinical signs compatible with tuberculosis but with the final diagnosis of infectious diseases different from tuberculosis. Here, we addressed the mechanisms involved and assessed potential alternative biomarkers to overcome indeterminate quantiferon results under these conditions.

Methods

Cytokine concentrations were measured in residual plasma from quantiferon assays performed in immunocompetent children (cases, median age: 3 years 9 months) with indeterminate results and community acquired pneumonia (n = 7) or meningoencephalitis (n = 1). Controls were age-matched immunocompetent children with determinate quantiferon results (infected with mycobacterium tuberculosis, n = 7 or not, n = 8).

Results

Lower IFN-γ expression in phytohemagglutinin-stimulated cultures from cases was accompanied by lower Th1 (IL-2, TNF-α, IP-10) and Th2 (IL-5, IL-13), but similar IL-10 secretion capacities as the controls.

Conclusions

A state of hyporesponsiveness that resembles the concept of immunoparalysis in severe infection was observed in children with milder infections. Though IP-10, IL-2, IL-5 and IL-13 were confirmed as promising alternative biomarkers for discriminating controls with and without tuberculosis in this study, defective induction of these biomarkers by phytohemagglutinin in cases precluded their usefulness in overcoming quantiferon indeterminate results in the above-mentioned clinical conditions.

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Keywords : Pediatrics, Quantiferon indeterminate results, Cytokines, IL-10, Common infections

Plan

Introduction

Materials and methods

Cases and controls

Immunological investigations

Statistical analysis

Results

Characteristics of the study population

Comparison of cytokine values in controls that are or not infected with M.tb confirmed IP-10, IL-2, IL-5 and IL-13 as promising alternative biomarkers for diagnosing TB

Low IFN-γ response to PHA in QFTB assay from immunocompetent children with on-going infectious diseases different from TB is accompanied by impaired Th1, Th2, Th17 cytokine and IP-10 chemokine secretion capacity, but a relatively more preserved IL-10 release

Discussion

Conflict of interest

Funding source

Authors contributions

☆	Data were previously presented at 32nd Annual ESPID meeting, Dublin–Ireland May 2014 (oral presentation) under the title: “Altered cytokine/chemokine responses to mitogen responsible for quantiferon indeterminate results in immunocompetent children ongoing acute infection”.

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Vol 71 - N° 2

P. 250-257 - août 2015 Retour au numéro

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Altered cytokine profiles in children with indeterminate quantiferon results and common infections - 01/07/15

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