title: IP-10 differentiates between active and latent tuberculosis irrespective of HIV status and declines during therapy.
abstract: OBJECTIVE
  Biomarkers for diagnosis and therapy efficacy in tuberculosis (TB) are requested. We have studied biomarkers that may differentiate between active and latent TB infection (LTBI), the influence of HIV infection and changes during anti-TB chemotherapy.
  
  
  METHODS
  Thirty-eight plasma cytokines, assessed by multiplex and enzyme immunoassays, were analyzed in patients with active TB before and during 24 weeks of anti-TB chemotherapy (n = 65), from individuals with LTBI (n = 34) and from QuantiFERON-TB (QFT) negative controls (n = 65). The study participants were grouped according to HIV status.
  
  
  RESULTS
  Plasma levels of the CXC chemokine IP-10 and soluble TNF receptor type 2 (sTNFr2) significantly differentiated active TB from the LTBI group, irrespective of HIV status. In the HIV-infected group the sensitivity and specificity was 100% for IP-10 with a cut-off of 2547 pg/mL. Plasma IP-10 declined gradually during anti-TB chemotherapy (12-24 weeks, p = 0.002) to a level comparable to LTBI and QFT negative control groups. sTNFr2 fluctuated throughout therapy, but was decreased after 12-24 weeks (p = 0.006).
  
  
  CONCLUSIONS
  IP-10 distinguished with high accuracy active TB from LTBI irrespective of HIV infection and declined during anti-TB chemotherapy. Plasma IP-10 may serve as a diagnostic biomarker to differentiate between the stages of TB infection and for monitoring therapy efficacy.
authors.affiliation: Department of Clinical Science, University of Bergen, N-5021 Bergen, Norway.
authors.forename: I
authors.initials: I
authors.lastname: Wergeland
authors.affiliation: Department of Internal Medicine, Section for Infectious Diseases, University Hospital of Northern Norway, N-9038 Tromsø, Norway; Department of Clinical Medicine, University of Tromsø, N-9037 Tromsø, Norway.
authors.forename: N
authors.initials: N
authors.lastname: Pullar
authors.affiliation: Center for Clinical Research, Haukeland University Hospital, N-5020 Bergen, Norway.
authors.forename: J
authors.initials: J
authors.lastname: Assmus
authors.affiliation: Institute of Clinical Medicine and K.G. Jebsen IRC, University of Oslo, N-0424 Oslo, Norway; Research Institute of Internal Medicine, Oslo University Hospital, N-0424 Oslo, Norway.
authors.forename: T
authors.initials: T
authors.lastname: Ueland
authors.affiliation: Institute of Clinical Medicine and K.G. Jebsen IRC, University of Oslo, N-0424 Oslo, Norway.
authors.forename: K
authors.initials: K
authors.lastname: Tonby
authors.affiliation: Institute of Clinical Medicine and K.G. Jebsen IRC, University of Oslo, N-0424 Oslo, Norway.
authors.forename: S
authors.initials: S
authors.lastname: Feruglio
authors.affiliation: Institute of Clinical Medicine and K.G. Jebsen IRC, University of Oslo, N-0424 Oslo, Norway; Department of Infectious Diseases, Oslo University Hospital, N-0424 Oslo, Norway.
authors.forename: D
authors.initials: D
authors.lastname: Kvale
authors.affiliation: Centre of Molecular Inflammation Research, Norwegian University of Science and Technology, Trondheim, Norway; Department of Infectious Diseases, St Olav's Hospital, Trondheim, Norway.
authors.forename: J K
authors.initials: JK
authors.lastname: Damås
authors.affiliation: Institute of Clinical Medicine and K.G. Jebsen IRC, University of Oslo, N-0424 Oslo, Norway; Research Institute of Internal Medicine, Oslo University Hospital, N-0424 Oslo, Norway; Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital, N-0424 Oslo, Norway.
authors.forename: P
authors.initials: P
authors.lastname: Aukrust
authors.affiliation: Institute of Clinical Medicine and K.G. Jebsen IRC, University of Oslo, N-0424 Oslo, Norway; Centre of Molecular Inflammation Research, Norwegian University of Science and Technology, Trondheim, Norway; Research Laboratory, Nordland Hospital, Bodø, and Faculty of Health Sciences, K.G. Jebsen TREC, University of Tromsø, Tromsø, Norway.
authors.forename: T E
authors.initials: TE
authors.lastname: Mollnes
authors.affiliation: Department of Clinical Science, University of Bergen, N-5021 Bergen, Norway; Institute of Clinical Medicine and K.G. Jebsen IRC, University of Oslo, N-0424 Oslo, Norway; Department of Infectious Diseases, Oslo University Hospital, N-0424 Oslo, Norway. Electronic address: a.m.d.riise@medisin.uio.no.
authors.forename: A M
authors.initials: AM
authors.lastname: Dyrhol-Riise
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D054357:Chemokine CXCL10 / Q000097:blood*; D060085:Coinfection; D016207:Cytokines / Q000097:blood; D005260:Female; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D007118:Immunoassay; D007371:Interferon-gamma / Q000097:blood; D055985:Latent Tuberculosis / Q000150:complications / Q000175:diagnosis* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D012680:Sensitivity and Specificity; D014376:Tuberculosis / Q000150:complications / Q000175:diagnosis* / Q000628:therapy; D055815:Young Adult
chemical_list: D015415:Biomarkers; D054357:Chemokine CXCL10; D016207:Cytokines; D007371:Interferon-gamma
keywords: Biomarker; Cytokines; HIV; IP-10; Therapy; Tuberculosis; sTNFr2