Latent Tuberculosis Infection Treatment and T-Cell Responses to Mycobacterium tuberculosis-specific Antigens

• Published in: American journal of respiratory and critical care medicine Vol. 175; no. 3; pp. 282 - 287
• Main Authors: Chee, Cynthia B. E, KhinMar, Kyi W, Gan, Suay H, Barkham, Timothy M. S, Pushparani, Mariappan, Wang, Yee T
• Format: Journal Article
• Language: English
• Published: New York, NY Am Thoracic Soc 01.02.2007; American Lung Association; American Thoracic Society
• Subjects: Adolescent; Adult; Aged; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Antigens; Antigens, Bacterial - drug effects; Antigens, Bacterial - immunology; Antigens, Bacterial - pharmacology; Bacterial Proteins - immunology; Bacterial Proteins - pharmacology; Biological and medical sciences; Blood. Blood and plasma substitutes. Blood products. Blood cells. Blood typing. Plasmapheresis. Apheresis; Bone marrow, stem cells transplantation. Graft versus host reaction; Cohort Studies; Female; Humans; Immunoassay; Infections; Intensive care medicine; Interferon; Interferon-gamma - analysis; Interferon-gamma - metabolism; Lymphocytes; Male; Medical sciences; Middle Aged; Mycobacterium; Mycobacterium tuberculosis; Peptides; Peptides - immunology; Peptides - pharmacology; Proteins; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Treatment Outcome; Tuberculosis; Tuberculosis, Pulmonary - drug therapy; Tuberculosis, Pulmonary - immunology; Singapore; Intensive care; Cytokine; culture filtrate protein 10; early secretory antigenic target 6-kD protein; Infection; Treatment; T-SPOT.TB; Mycobacterium tuberculosis; Mycobacteriales; T-Lymphocyte; Mycobacteriaceae; Bacteria; Actinomycetes; Antituberculous agent; Interferon; Antibacterial agent; Isoniazid; interferon-γ responses; Resuscitation
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/rccm.200608-1109OC

There is currently no available test for monitoring the effect of treatment of latent tuberculosis infection (LTBI) to indicate cure or predict risk of subsequent progression to disease. We used the T-SPOT.TB assay, which measures T-cell interferon-gamma responses to the Mycobacterium tuberculosis-specific peptides early secretory antigenic target 6-kD protein (ESAT-6) and culture filtrate protein 10 (CFP-10), to determine the effect of LTBI treatment on these responses. A total of 226 tuberculosis contacts with positive T-SPOT.TB results underwent repeat testing on LTBI treatment completion. The majority (96%) received 6 months of isoniazid. The pre- and post-treatment T-SPOT.TB results were analyzed according to the combined and separate responses to ESAT-6 and CFP-10 antigens. The T-SPOT.TB reverted to negative in 85 (37.6%) contacts at treatment completion. Treatment had a significant effect on the response to CFP-10 (p < 0.001; reversion rate, 48.6%), but not on the response to ESAT-6 (p = 0.081; reversion rate, 21.6%). The median number of spot-forming cells (SFCs)/2.5 x 10(5) peripheral blood mononuclear cells (PBMCs) pre- and post-treatment was 6 versus 4.5 for ESAT-6 (p = 0.116) and 11 versus 4 for CFP-10 (p < 0.001). There was a significant difference between the change (fall) in the pre- and post-treatment responses to CFP-10 (6 SFCs/2.5 x 10(5) PBMCs) and ESAT-6 (0 SFCs/2.5 x 10(5) PBMCs; p < 0.001). Significantly different age-related T-cell responses to the two antigens were found. LTBI treatment had a differential effect on T-cell responses to ESAT-6 and CFP-10 as measured by the T-SPOT.TB. The quantitative response to CFP-10 may be a useful LTBI treatment-monitoring tool.