Peripheral T cell cytokine responses for diagnosis of active tuberculosis

• Published in: PloS one 2012-04, Vol.7 (4), p.e35290-e35290
• Main Authors: Nemeth, Johannes, Winkler, Heide-Maria, Zwick, Ralph H, Müller, Catharina, Rumetshofer, Rudolf, Boeck, Lucas, Burghuber, Otto C, Winkler, Stefan
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Antigens; Antigens, Bacterial; Bacterial Proteins; Biological response modifiers; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Critical care; Cytokines; Cytokines - immunology; Diagnostic software; Diagnostic systems; Drug therapy; Enzymes; Epidemiology; Female; Fever; Health aspects; Hospitals; Humans; Immunization; Infections; Infectious diseases; Interferon; Interferon-gamma; Interleukin-2; Interleukins; Internal medicine; Lymphocytes; Lymphocytes T; Male; Medical diagnosis; Medicine; Middle Aged; Mycobacterium tuberculosis; Mycobacterium tuberculosis - immunology; Patients; Peripheral blood; T cell receptors; T cells; T-Lymphocytes - immunology; Tropical diseases; Tuberculin Test; Tuberculosis; Tuberculosis - diagnosis; Tumor necrosis factor-TNF; γ-Interferon
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0035290

A test for diagnosis of active Tuberculosis (TB) from peripheral blood could tremendously improve clinical management of patients. Of 178 prospectively enrolled patients with possible TB, 60 patients were diagnosed with pulmonary and 27 patients with extrapulmonary TB. The frequencies of Mycobacterium tuberculosis (MTB) specific CD4(+) T cells and CD8(+) T cells producing cytokines were assessed using overnight stimulation with purified protein derivate (PPD) or early secretory antigenic target (ESAT)-6, respectively. Among patients with active TB, an increased type 1 cytokine profile consisting of mainly CD4(+) T cell derived interferon (IFN)-γ was detectable. Despite contributing to the cytokine profile as a whole, the independent diagnostic performance of one cytokine producing T cells as well as polyfunctional T cells was poor. IFN-γ/Interleukin(IL)-2 cytokine ratios discriminated best between active TB and other diseases. T cells producing one cytokine and polyfunctional T cells have a limited role in diagnosis of active TB. The significant shift from a "memory type" to an "effector type" cytokine profile may be useful for further development of a rapid immune-diagnostic tool for active TB.