Altered cytokine profiles in children with indeterminate quantiferon results and common infections.
OBJECTIVE
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.
Laboratory of Immunology, Robert-Debré Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Univ. Paris Diderot, Sorbonne Paris Cité, 75019 Paris, France.
Mohamed
M
Jeljeli
Laboratory of Immunology, Robert-Debré Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Univ. Paris Diderot, Sorbonne Paris Cité, 75019 Paris, France.
Valérie
V
Guérin-El Khourouj
Department of Pediatric Infectious Disease, Robert-Debré Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Univ. Paris Diderot, Sorbonne Paris Cité, 75019 Paris, France.
Agathe
A
de Lauzanne
Laboratory of Immunology, Robert-Debré Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Univ. Paris Diderot, Sorbonne Paris Cité, 75019 Paris, France.
Marine
M
Armand
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.
Vibol
V
Chhor
Laboratory of Immunology, Robert-Debré Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Univ. Paris Diderot, Sorbonne Paris Cité, 75019 Paris, France.
Béatrice
B
Pédron
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.
Stéphane
S
Dauger
Department of Pediatric Gastroenterology, Robert Debré Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Univ. Paris Diderot, Sorbonne Paris Cité, 75019 Paris, France.
Jérôme
J
Viala
INSERM U1141, Robert-Debré Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Univ. Paris Diderot, Sorbonne Paris Cité, 75019 Paris, France.
Pierre
P
Gressens
Department of Pediatric Infectious Disease, Robert-Debré Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Univ. Paris Diderot, Sorbonne Paris Cité, 75019 Paris, France.
Albert
A
Faye
Laboratory of Immunology, Robert-Debré Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Univ. Paris Diderot, Sorbonne Paris Cité, 75019 Paris, France. Electronic address: ghislaine.sterkers@rdb.aphp.fr.
Ghislaine
G
Sterkers
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000097:blood*; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007223:Infant; D059425:Interferon-gamma Release Tests; D008297:Male; D008590:Meningoencephalitis / Q000175:diagnosis* / Q000276:immunology*; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D011014:Pneumonia / Q000175:diagnosis* / Q000276:immunology*; D012680:Sensitivity and Specificity
D016207:Cytokines
Common infections; Cytokines; IL-10; Pediatrics; Quantiferon indeterminate results