title: The effect of HIV coinfection, HAART and TB treatment on cytokine/chemokine responses to Mycobacterium tuberculosis (Mtb) antigens in active TB patients and latently Mtb infected individuals.
abstract: Identification of Mtb specific induced cytokine/chemokine host biomarkers could assist in developing novel diagnostic, prognostic and therapeutic tools for TB. Levels of IFN-γ, IL-2, IL-17, IL-10, IP-10 and MIP-1α were measured in supernatants of whole blood stimulated with Mtb specific fusion protein ESAT-6/CFP-10 using xMAP technology. The study groups were HIV positive TB patients (HIV(+)TB(+)), HIV negative TB patients (HIV(-)TB(+)), HIV positive tuberculin skin test positive (TST+) (HIV(+)TST(+)), HIV negative TST+ (HIV(-)TST(+)), and HIV(-)TST(-) individuals. Compared to HIV(-)TST(-), latent TB infection led to increased levels of IP-10, IFN-γ and IL-17, while levels of IL-2 and IP-10 were increased with active TB. Levels of IFN-γ, IL-17, MIP-1α, and IL-10 were increased in HIV(-)TST(+) individuals compared to HIV(-)TB(+) patients. HIV coinfection decreased the level of IFN-γ, IL-17, IP-10 and IL-2. After six months (M6) of anti-TB treatment (ATT) in HIV(-)TB(+) patients, IFN-γ, IL-10, and MIP-1α levels normalized. After M6 and M18 of ATT plus HAART in HIV(+)TB(+) patients, levels of MIP-1α and IL-10 normalized, while this was not the case for IFN-γ, IL-2, IL-17, and IP-10 levels. In HIV(+)TST(+) patients on HAART, levels of IFN-γ, IL-17, IL-10 and MIP-1α normalized, while no change in the levels of IL-2 and IP-10 were observed. In conclusion, the simultaneous measurement of IFN-γ, IL-17 and IP-10 may assist in diagnosing LTBI; IL-2 and IP-10 may assist in diagnosing active TB; while IFN-γ, IL-17, MIP-1α, and IL-10 levels could help to discriminate LTBI and active TB. In addition, IL-10 and MIP-1α levels could help to monitor responses to TB treatment and HAART.
authors.affiliation: HIV/AIDS and Tuberculosis Research Directorate, Ethiopian Health and Nutrition Research Institute (EHNRI), Addis Ababa, Ethiopia; Department of Internal Medicine and Infectious Diseases, Laboratory of Transitional Immunology, Department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands. Electronic address: dkassa2003@gmail.com.
authors.forename: Desta
authors.initials: D
authors.lastname: Kassa
authors.affiliation: Department of Internal Medicine and Infectious Diseases, Department of Pediatric Immunology, Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands. Electronic address: wjager@umcutrecht.nl.
authors.forename: Wilco
authors.initials: W
authors.lastname: de Jager
authors.affiliation: HIV/AIDS and Tuberculosis Research Directorate, Ethiopian Health and Nutrition Research Institute (EHNRI), Addis Ababa, Ethiopia. Electronic address: gereachem@yahoo.com.
authors.forename: Gebremedhin
authors.initials: G
authors.lastname: Gebremichael
authors.affiliation: HIV/AIDS and Tuberculosis Research Directorate, Ethiopian Health and Nutrition Research Institute (EHNRI), Addis Ababa, Ethiopia. Electronic address: yudanet@gmail.com.
authors.forename: Yodit
authors.initials: Y
authors.lastname: Alemayehu
authors.affiliation: Department of Internal Medicine and Infectious Diseases, Laboratory of Transitional Immunology, Department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands. Electronic address: leonie.ran@roche.com.
authors.forename: Leonie
authors.initials: L
authors.lastname: Ran
authors.affiliation: Department of Internal Medicine and Infectious Diseases, Laboratory of Transitional Immunology, Department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands. Electronic address: j.h.fransen@umcutrecht.nl.
authors.forename: Justin
authors.initials: J
authors.lastname: Fransen
authors.affiliation: Medical Biotech Laboratory, Addis Ababa, Ethiopia. Electronic address: dawwol@gmail.com.
authors.forename: Dawit
authors.initials: D
authors.lastname: Wolday
authors.affiliation: HIV/AIDS and Tuberculosis Research Directorate, Ethiopian Health and Nutrition Research Institute (EHNRI), Addis Ababa, Ethiopia. Electronic address: tmessele@aslm.org.
authors.forename: Tsehaynesh
authors.initials: T
authors.lastname: Messele
authors.affiliation: HIV/AIDS and Tuberculosis Research Directorate, Ethiopian Health and Nutrition Research Institute (EHNRI), Addis Ababa, Ethiopia. Electronic address: bt2362@columbia.edu.
authors.forename: Belete
authors.initials: B
authors.lastname: Tegbaru
authors.affiliation: Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: T.H.M.Ottenhoff@lumc.nl.
authors.forename: Tom H M
authors.initials: TH
authors.lastname: Ottenhoff
authors.affiliation: Department of Internal Medicine and Infectious Diseases, Laboratory of Transitional Immunology, Department of Immunology, University Medical Center Utrecht, Utrecht, The Netherlands. Electronic address: debbie.van.baarle@rivm.nl.
authors.forename: Debbie
authors.initials: D
authors.lastname: van Baarle
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D000942:Antigens, Bacterial / Q000097:blood / Q000276:immunology*; D023241:Antiretroviral Therapy, Highly Active; D000995:Antitubercular Agents / Q000627:therapeutic use*; D018925:Chemokines / Q000097:blood / Q000276:immunology*; D016207:Cytokines / Q000097:blood / Q000276:immunology*; D003937:Diagnosis, Differential; D005002:Ethiopia; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D006801:Humans; D055985:Latent Tuberculosis / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D011237:Predictive Value of Tests; D011993:Recombinant Fusion Proteins / Q000276:immunology; D013997:Time Factors; D016896:Treatment Outcome; D014374:Tuberculin Test; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D000942:Antigens, Bacterial; D000995:Antitubercular Agents; D018925:Chemokines; D016207:Cytokines; C505464:ESAT-6-CFP10 fusion protein; D011993:Recombinant Fusion Proteins
keywords: Biomarkers; Cytokines; HIV/AIDS; Tuberculosis