title: Multiple cytokines for the detection ofMycobacterium tuberculosisinfection in children with tuberculosis.
abstract: Interferon-gamma (IFN-γ) release assays (IGRAs) play an important role in the diagnosis of Mycobacterium tuberculosis infection. However, in children with tuberculosis (TB), some studies have shown increased frequencies of false-negative or indeterminate IGRA results.
  
  
  
  To analyse the spectrum of different cytokines to improve the diagnostic accuracy of IGRAs in latent tuberculous infection (LTBI) and active TB.
  
  
  
  We performed multiplex cytokine expression analysis of QuantiFERON® Gold In-Tube supernatants in children with active TB (n = 21) and disease-free contacts with (n = 15) and without LTBI (n = 12), to determine the sensitivity and specificity of the modified tests.
  
  
  
  Of 21 initial cytokines analysed, IFN-γ and six other candidates (interleukin [IL] 2, inducible protein 10 [IP-10], IL-13, IL-1α, tumour necrosis factor alpha [TNF-α] and granulocyte-macrophage colony-stimulating factor [GM-CSF]) were significantly more elevated in children with TB and those with LTBI than in the non-infected controls. Sensitivity and specificity were similar for IFN-γ and IL-2, but lower for the remaining candidates. Notably, a subset of candidates, including IP-10, showed M. tuberculosis antigen-induced specific expression in non-infected children. None of the candidates showed differences in expression between children with TB and those with LTBI.
  
  
  
  Our results did not suggest that alternative IGRA cytokines can distinguish between children with active TB and those with LTBI. IFN-γ and IL-2 showed comparable capacity in diagnosing M. tuberculosis infection in our study groups.
authors.affiliation: Paediatric Infectious Diseases Group, Department of General Paediatrics, Neonatology and Paediatric Cardiology, University Children's Hospital, Dusseldorf.
authors.forename: N
authors.initials: N
authors.lastname: Nausch
authors.affiliation: Paediatric Infectious Diseases Group, Department of General Paediatrics, Neonatology and Paediatric Cardiology, University Children's Hospital, Dusseldorf.
authors.forename: C
authors.initials: C
authors.lastname: Lundtoft
authors.affiliation: Department of Paediatric Pneumology and Immunology, Charité-Universitätsmedizin Berlin, Berlin.
authors.forename: G
authors.initials: G
authors.lastname: Schulz
authors.affiliation: Department of Paediatric Pneumology and Immunology, Charité-Universitätsmedizin Berlin, Berlin.
authors.forename: H
authors.initials: H
authors.lastname: Henckel
authors.affiliation: Paediatric Infectious Diseases Group, Department of General Paediatrics, Neonatology and Paediatric Cardiology, University Children's Hospital, Dusseldorf.
authors.forename: E
authors.initials: E
authors.lastname: Mayatepek
authors.affiliation: Department of Immunology, Bernhard-Nocht Institute for Tropical Medicine, Hamburg, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Fleischer
authors.affiliation: Department of Paediatric Pneumology and Immunology, Charité-Universitätsmedizin Berlin, Berlin, Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut, USA.
authors.forename: F M
authors.initials: FM
authors.lastname: Marx
authors.affiliation: Paediatric Infectious Diseases Group, Department of General Paediatrics, Neonatology and Paediatric Cardiology, University Children's Hospital, Dusseldorf, Department of Immunology, Bernhard-Nocht Institute for Tropical Medicine, Hamburg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Jacobsen
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000378:metabolism*; D005189:False Positive Reactions; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000378:metabolism; D059425:Interferon-gamma Release Tests / Q000379:methods*; D007376:Interleukin-2 / Q000378:metabolism; D055985:Latent Tuberculosis / Q000175:diagnosis*; D009169:Mycobacterium tuberculosis / Q000302:isolation & purification; D012680:Sensitivity and Specificity; D014376:Tuberculosis / Q000175:diagnosis*
chemical_list: D016207:Cytokines; D007376:Interleukin-2; D007371:Interferon-gamma