title: In vitro QuantiFERON-TB gold antigen specific interleukin-1beta to diagnose TB among HIV-positive subjects.
abstract: BACKGROUND
  The recently introduced IFN-γ release assay (IGRA) has been reported to improve the diagnosis of TB. However, IGRA has suboptimal sensitivity to diagnose TB among HIV co-infected subjects. Apart from IFN-γ, the pro inflammatory cytokines such as Interleukin-1beta (IL-1β), Tumor necrosis factor-alpha (TNF-α), IL-2, IL-6, IL-8 and IL-12 are also play a major role in mycobacterial infections. This study aimed to analyze these cytokines for detecting active TB among HIV sero positive subjects.
  
  
  METHODS
  We had prospectively enrolled 53 HIV positive subjects and 55 HIV-TB co-infected patients from India. IGRA was performed by using QuantiFERON TB-Gold In tube (QFT-GIT) method. TB antigen specific IL-1β, TNF-α, IL-2, IL-6, IL-8 and IL-12 levels were evaluated by ELISA in plasma harvested from QFT-GIT tubes.
  
  
  CONCLUSIONS
  The TB antigen specific IL-1β levels were significantly elevated in HIV-TB co-infected patients compared to HIV positive subjects (p = 0.0004). The specificity of both IL-1β (50.94%) and QFT-GIT (52.83%) remained similar in HIV positive subjects (p = 0.24). However, IL-1β had shown higher sensitivity (72.73%) than QFT-GIT (54.55%) to diagnose TB among HIV co-infected patients. Moreover, in culture test positive HIV-TB patients, antigen specific IL-1β exhibited sensitivity of 84.21%; whereas QFT-GIT exhibited only 57.89% sensitivity. Unlike IFN-γ (the read out marker of QFT-GIT), antigen specific IL-1β levels were not influenced by low CD4 counts. The other cytokine levels were not significantly differ between the 2 groups.From this study we concluded that TB antigen specific IL-1β may be an additional biomarker for active TB diagnosis among HIV positive subjects.
authors.affiliation: Department of Immunology, National Institute for Research in Tuberculosis (ICMR), No. 1, Mayor Sathyamoorthy Road, Chetpet, Chennai, 600 031, Tamil Nadu, India. Electronic address: prabha.biochem1@gmail.com.
authors.forename: Maddineni
authors.initials: M
authors.lastname: Prabhavathi
authors.affiliation: Cardiovascular Division, Sidra Medical and Research Center, Doha, Qatar. Electronic address: bkabeer@sidra.org.
authors.forename: Basirudeen Syed
authors.initials: BS
authors.lastname: Ahamed Kabeer
authors.affiliation: Department of Immunology, National Institute for Research in Tuberculosis (ICMR), No. 1, Mayor Sathyamoorthy Road, Chetpet, Chennai, 600 031, Tamil Nadu, India. Electronic address: harianbu1@gmail.com.
authors.forename: Anbarasu
authors.initials: A
authors.lastname: Deenadayalan
authors.affiliation: Department of Immunology, National Institute for Research in Tuberculosis (ICMR), No. 1, Mayor Sathyamoorthy Road, Chetpet, Chennai, 600 031, Tamil Nadu, India. Electronic address: alameluraja@gmail.com.
authors.forename: Alamelu
authors.initials: A
authors.lastname: Raja
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D018791:CD4 Lymphocyte Count; D060085:Coinfection; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000150:complications* / Q000175:diagnosis / Q000276:immunology; D006801:Humans; D007194:India; D007371:Interferon-gamma / Q000097:blood / Q000276:immunology; D059425:Interferon-gamma Release Tests; D053583:Interleukin-1beta / Q000097:blood* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D015203:Reproducibility of Results; D014376:Tuberculosis / Q000097:blood / Q000150:complications / Q000175:diagnosis* / Q000276:immunology / Q000382:microbiology; D055815:Young Adult
chemical_list: D015415:Biomarkers; C573415:IFNG protein, human; C508585:IL1B protein, human; D053583:Interleukin-1beta; D007371:Interferon-gamma