IP-10 differentiates between active and latent tuberculosis irrespective of HIV status and declines during therapy

I Wergeland; N Pullar; J Assmus; T Ueland; K Tonby; S Feruglio; D Kvale; J K Damås; P Aukrust; T E Mollnes; A M Dyrhol-Riise

doi:10.1016/j.jinf.2014.12.019

IP-10 differentiates between active and latent tuberculosis irrespective of HIV status and declines during therapy

J Infect. 2015 Apr;70(4):381-91. doi: 10.1016/j.jinf.2014.12.019. Epub 2015 Jan 15.

Authors

I Wergeland¹, N Pullar², J Assmus³, T Ueland⁴, K Tonby⁵, S Feruglio⁵, D Kvale⁶, J K Damås⁷, P Aukrust⁸, T E Mollnes⁹, A M Dyrhol-Riise¹⁰

Affiliations

¹ Department of Clinical Science, University of Bergen, N-5021 Bergen, Norway.
² 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.
³ Center for Clinical Research, Haukeland University Hospital, N-5020 Bergen, Norway.
⁴ 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.
⁵ Institute of Clinical Medicine and K.G. Jebsen IRC, University of Oslo, N-0424 Oslo, Norway.
⁶ 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.
⁷ Centre of Molecular Inflammation Research, Norwegian University of Science and Technology, Trondheim, Norway; Department of Infectious Diseases, St Olav's Hospital, Trondheim, Norway.
⁸ 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.
⁹ 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.
¹⁰ 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.

PMID: 25597826
DOI: 10.1016/j.jinf.2014.12.019

Abstract

Objectives: 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.

Keywords: Biomarker; Cytokines; HIV; IP-10; Therapy; Tuberculosis; sTNFr2.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Aged
Aged, 80 and over
Biomarkers / blood
Chemokine CXCL10 / blood*
Coinfection
Cytokines / blood
Female
HIV Infections / complications*
Humans
Immunoassay
Interferon-gamma / blood
Latent Tuberculosis / complications
Latent Tuberculosis / diagnosis*
Latent Tuberculosis / therapy
Male
Middle Aged
Sensitivity and Specificity
Tuberculosis / complications
Tuberculosis / diagnosis*
Tuberculosis / therapy
Young Adult

Substances

Biomarkers
Chemokine CXCL10
Cytokines
Interferon-gamma