title: Potential Role for Mycobacterium tuberculosis Specific IL-2 and IFN-γ Responses in Discriminating between Latent Infection and Active Disease after Long-Term Stimulation.
abstract: Interferon gamma release assays (IGRAs) could accurately diagnose Mycobacterium tuberculosis (M.tuberculosis) infection. However, these assays do not discriminate between latent tuberculosis infection (LTBI) and active tuberculosis disease (ATB). Here, a total of 177 subjects, including 65 patients with ATB, 43 subjects with LTBI, and 69 TB-uninfected controls (CON group) were enrolled. The concentration of IFN-γ, IP-10, and IL-2 was determined in peripheral blood mononuclear cells (PBMCs) after short-term (24h) or long-term (72h) stimulation with TB antigens including ESAT-6/CFP-10 (EC) and purified protein derivative (PPD).EC-stimulated IL-2 and gamma interferon-inducible protein 10 (IP-10) release (24h and 72h) showed a good diagnostic performance in distinguishing between TB-infected and TB-uninfected individuals, but failed to discriminate between ATB and LTBI. After 72h of incubation, the release of IL-2 was higher in LTBI patients after stimulation with EC and PPD. The PPD-stimulated IL-2/IFN-γ ratio after 72h incubation had the diagnostic potential to discriminate between ATB and LTBI, with a sensitivity of 90.8% and a specificity of 97.7%. In addition, these new biomarkers, combined with T-SPOT test in a two-step strategy, were validated with high levels of accuracy in a prospective clinical-based cohort. Collectively, the PPD-stimulated IL-2/IFN-γ ratio after long-term incubation may be an alternative diagnostic biomarker in distinguishing between active TB patients and subjects with latent infection.
authors.affiliation: Clinic and Research Center of Tuberculosis, Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Sun
authors.affiliation: Clinic and Research Center of Tuberculosis, Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.affiliation: Clinic and Research Center of Tuberculosis, Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Sha
mesh_terms: D000328:Adult; D000368:Aged; D000942:Antigens, Bacterial / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology; D015415:Biomarkers / Q000032:analysis; D003141:Communicable Diseases / Q000175:diagnosis*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D059425:Interferon-gamma Release Tests; D007376:Interleukin-2 / Q000378:metabolism*; D055985:Latent Tuberculosis / Q000175:diagnosis* / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D011446:Prospective Studies; D014374:Tuberculin Test; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology; D055815:Young Adult
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D015415:Biomarkers; C117940:CFP-10 protein, Mycobacterium tuberculosis; C093276:ESAT-6 protein, Mycobacterium tuberculosis; C508594:IL2 protein, human; D007376:Interleukin-2; D007371:Interferon-gamma