title: Granzyme B as a diagnostic marker of tuberculosis in patients with and without HIV coinfection.
abstract: Immunodiagnostic tests for tuberculosis (TB) are based on the estimation of interferon γ (IFN-γ) or IFN-γ-secreting CD4(+) T cells following ex vivo stimulation with ESAT6 and CFP-10. Sensitivity of these tests is likely to be compromised in CD4(+) T-cell-depleted situations, like HIV-TB coinfection. CD4(+) and CD8(+) T cells, isolated from 3 groups, viz., HIV-negative patients with active TB, HIV-TB coinfected patients, and healthy household contacts (HHCs) were cocultivated with autologous dendritic cells, and the cytokine response to rESAT6 stimulation was compared between groups in supernatants. While CD4(+) T-cell stimulation yielded significantly elevated levels of IFN-γ and interleukin 4 in HIV-negative TB patients, compared to HHCs, the levels of both these cytokines were nondiscriminatory between HIV-positive TB patients and HHCs. However, CD8(+) T-cell stimulation yielded significantly elevated granzyme B titers in both groups of patients, irrespective of HIV coinfection status. Hence, contrary to IFN-γ, granzyme B might be a useful diagnostic marker for Mycobacterium tuberculosis infection particularly in HIV coinfected patients.
authors.affiliation: Department of Microbiology, Himalayan Institute of Medical Sciences, Swami Ram Nagar, Jolly Grant, Dehradun 248140, India. Electronic address: pronoti7@gmail.com.
authors.forename: Pronoti
authors.initials: P
authors.lastname: Sarkar
authors.affiliation: Department of Microbiology, Himalayan Institute of Medical Sciences, Swami Ram Nagar, Jolly Grant, Dehradun 248140, India. Electronic address: saumik.mitra@gmail.com.
authors.forename: Soumik
authors.initials: S
authors.lastname: Mitra
authors.affiliation: Department of Microbiology, Himalayan Institute of Medical Sciences, Swami Ram Nagar, Jolly Grant, Dehradun 248140, India. Electronic address: priyannk_molecular@rediffmail.com.
authors.forename: Priyannk
authors.initials: P
authors.lastname: Pant
authors.affiliation: Department of Microbiology, Himalayan Institute of Medical Sciences, Swami Ram Nagar, Jolly Grant, Dehradun 248140, India. Electronic address: aartiraghuvanshi@yahoo.co.in.
authors.forename: Aarti
authors.initials: A
authors.lastname: Kotwal
authors.affiliation: Department of Microbiology, Himalayan Institute of Medical Sciences, Swami Ram Nagar, Jolly Grant, Dehradun 248140, India. Electronic address: drbarnali05@rediffmail.com.
authors.forename: Barnali
authors.initials: B
authors.lastname: Kakati
authors.affiliation: Department of Microbiology, Himalayan Institute of Medical Sciences, Swami Ram Nagar, Jolly Grant, Dehradun 248140, India. Electronic address: vmsahota@gmail.com.
authors.forename: Victor
authors.initials: V
authors.lastname: Masih
authors.affiliation: Department of Pulmonary Medicine, Himalayan Institute of Medical Sciences, Swami Ram Nagar, Jolly Grant, Dehradun 248140, India. Electronic address: girish_sindhwani@rediffmail.com.
authors.forename: Girish
authors.initials: G
authors.lastname: Sindhwani
authors.affiliation: Department of Microbiology, Himalayan Institute of Medical Sciences, Swami Ram Nagar, Jolly Grant, Dehradun 248140, India. Electronic address: dbiswas71@rediffmail.com.
authors.forename: Debasis
authors.initials: D
authors.lastname: Biswas
mesh_terms: D000293:Adolescent; D000328:Adult; D000942:Antigens, Bacterial / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology; D060085:Coinfection; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D053804:Granzymes / Q000378:metabolism*; D015658:HIV Infections; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology; D054353:Perforin / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D014376:Tuberculosis / Q000175:diagnosis* / Q000276:immunology / Q000378:metabolism*; D055815:Young Adult
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D016207:Cytokines; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D054353:Perforin; D007371:Interferon-gamma; D053804:Granzymes
keywords: CD8(+) T-cell; Granzyme B; HIV-TB coinfection; Immunodiagnosis; Tuberculosis; rESAT-6