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Published ahead of print on November 2, 2006, doi:10.1164/rccm.200608-1109OC
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American Journal of Respiratory and Critical Care Medicine Vol 175. pp. 282-287, (2007)
© 2007 American Thoracic Society
doi: 10.1164/rccm.200608-1109OC

Original Article

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

Cynthia B. E. Chee, Kyi W. KhinMar, Suay H. Gan, Timothy M. S. Barkham, Mariappan Pushparani and Yee T. Wang

Singapore Tuberculosis Control Unit, Department of Clinical Epidemiology, and Department of Pathology and Laboratory Medicine, Tan Tock Seng Hospital, Singapore, Singapore

Correspondence and requests for reprints should be addressed to Cynthia Bin-Eng Chee, M.B. B.S., F.R.C.P., TB Control Unit, Department of Respiratory Medicine, Tan Tock Seng Hospital, 11 Jalan Tan Tock Seng, Singapore 308433, Singapore. E-mail: cynthia_chee{at}ttsh.com.sg

Rationale: 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.

Objective: 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.

Methods: 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.

Results: 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 105 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 105 PBMCs) and ESAT-6 (0 SFCs/2.5 x 105 PBMCs; p < 0.001). Significantly different age-related T-cell responses to the two antigens were found.

Conclusion: 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.

Key Words: T-SPOT.TB • early secretory antigenic target 6-kD protein • culture filtrate protein 10 • interferon-{gamma} • responses • isoniazid


AT A GLANCE COMMENTARY

Scientific Knowledge on the Subject
Scientific knowledge pertaining to the influence of latent TB infection treatment on the T-cell responses to M. tuberculosis-specific antigens is sparse.

What This Study Adds to the Field
We found a differential effect of latent tuberculosis infection treatment on T-cell responses to the Mycobacterium tuberculosis–specific antigens, with a significant effect on the response to CFP-10, but not to ESAT-6.

 



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