title: Granzyme A as a potential biomarker of Mycobacterium tuberculosis infection and disease.
abstract: Cytotoxic molecules such as granulysin, perforin and granzymes produced by cytolytic T cells directly contribute to immune defense against tuberculosis (TB). In search for novel TB biomarkers, we have evaluated the levels of granzyme A in plasma obtained from QuantiFERON-TB Gold In tube (QFT-IT) assays from patients with active TB disease and subjects with latent TB infection (LTBI). Granzyme A serum levels in TB patients were significantly lower than values found in LTBI subjects even after subtraction of the unstimulated levels from the antigen-stimulated responses. The receiver operator characteristics (ROC) curve analysis comparing TB patients and LTBI groups, showed that at a cut-off value of granzyme A of <3.425pg/ml, the sensitivity and the specificity of the assay were 29.41% and 94.74%, respectively. Our results suggest that granzyme A could be considered another biomarker of TB, that can be used, other than IFN-γ, to discriminate between patients with active TB and LTBI subjects in a well characterized cohort of confirmed Mycobacterium tuberculosis-infected individuals.
authors.affiliation: Central Laboratory of Advanced Diagnosis and Biomedical Research (CLADIBIOR), Università di Palermo, Palermo, Italy; Dipartimento di Biopatologia e Biotecnologie Mediche, Università di Palermo, Palermo, Italy.
authors.forename: Giuliana
authors.initials: G
authors.lastname: Guggino
authors.affiliation: Central Laboratory of Advanced Diagnosis and Biomedical Research (CLADIBIOR), Università di Palermo, Palermo, Italy; Dipartimento di Biopatologia e Biotecnologie Mediche, Università di Palermo, Palermo, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Orlando
authors.affiliation: Central Laboratory of Advanced Diagnosis and Biomedical Research (CLADIBIOR), Università di Palermo, Palermo, Italy; Dipartimento di Biopatologia e Biotecnologie Mediche, Università di Palermo, Palermo, Italy.
authors.forename: Stella
authors.initials: S
authors.lastname: Cutrera
authors.affiliation: Central Laboratory of Advanced Diagnosis and Biomedical Research (CLADIBIOR), Università di Palermo, Palermo, Italy; Dipartimento di Biopatologia e Biotecnologie Mediche, Università di Palermo, Palermo, Italy.
authors.forename: Marco P
authors.initials: MP
authors.lastname: La Manna
authors.affiliation: Central Laboratory of Advanced Diagnosis and Biomedical Research (CLADIBIOR), Università di Palermo, Palermo, Italy; Dipartimento di Biopatologia e Biotecnologie Mediche, Università di Palermo, Palermo, Italy.
authors.forename: Diana
authors.initials: D
authors.lastname: Di Liberto
authors.affiliation: Institute for Infectious Diseases L. Spallanzani, Rome, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Vanini
authors.affiliation: Institute for Infectious Diseases L. Spallanzani, Rome, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Petruccioli
authors.affiliation: Central Laboratory of Advanced Diagnosis and Biomedical Research (CLADIBIOR), Università di Palermo, Palermo, Italy; Dipartimento di Biopatologia e Biotecnologie Mediche, Università di Palermo, Palermo, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Dieli
authors.affiliation: Institute for Infectious Diseases L. Spallanzani, Rome, Italy.
authors.forename: Delia
authors.initials: D
authors.lastname: Goletti
authors.affiliation: Central Laboratory of Advanced Diagnosis and Biomedical Research (CLADIBIOR), Università di Palermo, Palermo, Italy; Dipartimento di Biopatologia e Biotecnologie Mediche, Università di Palermo, Palermo, Italy. Electronic address: nadia.caccamo@unipa.it.
authors.forename: Nadia
authors.initials: N
authors.lastname: Caccamo
mesh_terms: D000328:Adult; D000942:Antigens, Bacterial / Q000276:immunology; D015415:Biomarkers; D016022:Case-Control Studies; D005260:Female; D053804:Granzymes / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000097:blood / Q000378:metabolism; D055985:Latent Tuberculosis / Q000175:diagnosis / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D012372:ROC Curve; D014376:Tuberculosis / Q000175:diagnosis / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology / Q000517:prevention & control; D055815:Young Adult
chemical_list: D000942:Antigens, Bacterial; D015415:Biomarkers; D007371:Interferon-gamma; D053804:Granzymes
keywords: Disease; Granzyme A; IFN-γ; IGRA tests; Infection; Tuberculosis