title: Interferon-gamma inducible protein 10 as a biomarker for active tuberculosis and latent tuberculosis infection in children: a case-control study.
abstract: BACKGROUND
  Interferon-gamma (IFN-γ) release assays (IGRAs) are suboptimally sensitive to diagnose tuberculosis (TB) and latent TB infection (LTBI) in young children. In this study we compared Mycobacterium tuberculosis antigen-stimulated IFN-γ inducible protein 10 (IP-10) responses in children with active TB and LTBI to responses from children with non-tuberculous mycobacterial (NTM) lymphadenopathy and respiratory tract infection (RTI). We also assessed test agreement between IP-10 and the QuantiFERON(®)-TB Gold In-Tube (QFT-IT) test results, and investigated whether IP-10 release upon mitogen stimulation is associated with age.
  
  
  METHODS
  We recruited 48 children (median age 54 months) diagnosed in Germany with either active TB (n = 11), LTBI (n = 14), NTM lymphadenopathy (n = 8), or common RTI (n = 15). IFN-γ levels were measured using the QFT-IT. These plasma supernatants were used to determine IP-10 concentrations using an in-house enzyme-linked immunosorbent assay (ELISA).
  
  
  RESULTS
  The median antigen-stimulated IP-10 levels in children with active TB, LTBI, NTM lymphadenopathy, and RTI were 12,702 pg/ml, 9109 pg/ml, 97 pg/ml, and 84 pg/ml, respectively. We observed a strong correlation between IP-10 and IFN-γ plasma concentration in children with active TB and LTBI (r(2) = 0.69). Overall agreement between IP-10 and QFT-IT assays was high (kappa = 0.95). IP-10 levels after mitogen stimulation showed no association with age.
  
  
  CONCLUSIONS
  IP-10 and IFN-γ were both induced with antigen stimulation in blood from children in the TB and LTBI groups, in contrast to the NTM and RTI groups. Compared to IFN-γ the IP-10 levels were higher and IP-10 was released independently of age. IP-10 therefore may represent an additional biomarker in the paediatric population.
authors: Department of Paediatric Pneumology and Immunology, Charité Universitätsmedizin Berlin, Berlin, Germany. neele_alsleben@gmx.de
authors: Neele
authors: N
authors: Alsleben
authors: Morten
authors: M
authors: Ruhwald
authors: Holger
authors: H
authors: Rüssmann
authors: Florian M
authors: FM
authors: Marx
authors: Ulrich
authors: U
authors: Wahn
authors: Klaus
authors: K
authors: Magdorf
mesh_terms: D000942:Antigens, Bacterial / Q000276:immunology; D015415:Biomarkers / Q000032:analysis / Q000097:blood / Q000378:metabolism; D016022:Case-Control Studies; D054357:Chemokine CXCL10 / Q000032:analysis / Q000097:blood / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D007159:Immunologic Tests / Q000379:methods*; D007223:Infant; D007371:Interferon-gamma / Q000032:analysis / Q000097:blood / Q000378:metabolism; D059425:Interferon-gamma Release Tests; D055985:Latent Tuberculosis / Q000097:blood / Q000175:diagnosis / Q000276:immunology / Q000378:metabolism*; D008206:Lymphatic Diseases; D008297:Male; D011933:Reagent Kits, Diagnostic; D012141:Respiratory Tract Infections; D018709:Statistics, Nonparametric; D014376:Tuberculosis / Q000097:blood / Q000175:diagnosis / Q000276:immunology / Q000378:metabolism*
chemical_list: D000942:Antigens, Bacterial; D015415:Biomarkers; D054357:Chemokine CXCL10; D011933:Reagent Kits, Diagnostic; D007371:Interferon-gamma