title: Improving T-cell assays for the diagnosis of latent TB infection: potential of a diagnostic test based on IP-10.
abstract: BACKGROUND
  There is a need for simple tools such as the M.tuberculosis specific IFN-gamma release assays (IGRA) to improve diagnosis of M.tuberculosis-infection in children. The aim of the study was to evaluate the performance of an IP-10 and IL-2 based tests for the diagnosis of M.tuberculosis-infection in recently exposed children from Nigeria.
  
  
  RESULTS
  Samples were obtained from 59 children at high risk of infection with M.tuberculosis (contacts of adults with smear and culture-positive tuberculosis) and 61 at low risk (contacts of smear-negative/culture-positive tuberculosis or community controls). IP-10 and IL-2 was measured in plasma after stimulation of whole-blood with M.tuberculosis specific antigens and mitogen. Previously developed criteria for positive IP-10 and IL-2 tests were used and the diagnostic performances of the IP-10 and IL-2 tests were compared with the Quantiferon In-Tube (QFT-IT) and the Tuberculin Skin Tests (TST). In response to M.tuberculosis specific antigens, the high-risk children expressed significantly higher levels of IP-10 (1358 pg/ml[IQR 278-2535 pg/ml]) and IL-2 (164 pg/ml[11-590 pg/ml]) than low risk groups 149 pg/ml(25-497 pg/ml), and 0 pg/ml(0-3 pg/ml), respectively. There was excellent agreement (>89%,k>0.80) between IP-10, IL-2 tests and QFT-IT, better than with TST (>74%,k>0.49). The IP-10 and IL-2 responses were strongly associated with M.tuberculosis exposure and with grade of infectiousness of the index cases (p<0.0001). IP-10, IL-2, and TST but not QFT-IT was associated with age of the child in the low risk groups (p<0.02).
  
  
  CONCLUSIONS
  IP-10 is expressed in high levels and results of the IP-10 test were comparable to the QFT-IT. IL-2 was released in low amounts in response to the antigens and not in response to the mitogen therefore IL-2 seems a less useful marker. We have demonstrated that IP-10 and possibly IL-2 could be alternative or adjunct markers to IFN-gamma in the diagnosis infection with M.tuberculosis.
authors.affiliation: Department of Infectious Diseases 144, Copenhagen University, Hvidovre Hospital, Hvidovre, Denmark. mruhwald@mail.dk
authors.forename: Morten
authors.initials: M
authors.lastname: Ruhwald
authors.forename: Janne
authors.initials: J
authors.lastname: Petersen
authors.forename: Kristian
authors.initials: K
authors.lastname: Kofoed
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakaoka
authors.forename: Luis Eduardo
authors.initials: LE
authors.lastname: Cuevas
authors.forename: Lovett
authors.initials: L
authors.lastname: Lawson
authors.forename: Stephen Bertil
authors.initials: SB
authors.lastname: Squire
authors.forename: Jesper
authors.initials: J
authors.lastname: Eugen-Olsen
authors.forename: Pernille
authors.initials: P
authors.lastname: Ravn
mesh_terms: D000293:Adolescent; D054357:Chemokine CXCL10 / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D007376:Interleukin-2 / Q000097:blood; D008297:Male; D009549:Nigeria; D012680:Sensitivity and Specificity; D013601:T-Lymphocytes / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D014376:Tuberculosis / Q000175:diagnosis* / Q000276:immunology
chemical_list: C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D007376:Interleukin-2; D007371:Interferon-gamma