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Published ahead of print on November 2, 2006, doi:10.1164/rccm.200608-1109OC

Am. J. Respir. Crit. Care Med., Volume 175, Number 3, February 2007, 282-287

A more recent version of this article appeared on February 1, 2007
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Submitted on August 8, 2006
Accepted on November 2, 2006

Latent Tuberculosis Infection Treatment and T-cell responses to M. tuberculosis-Specific Antigens

Cynthia BE Chee1*, Kyi W KhinMar2, Suay H Gan1, Timothy MS Barkham3, Mariappan Pushparani1, and Yee T Wang1

1 Singapore Tuberculosis Control Unit, Tan Tock Seng Hospital, Singapore, Singapore, 2 Department of Clinical Epidemiology, Tan Tock Seng Hospital, Singapore, Singapore, 3 Department of Pathology and Laboratory Medicine, Tan Tock Seng Hospital, Singapore, Singapore

* To whom correspondence should be addressed. 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 (IFN{gamma}) responses to Mycobacterium tuberculosis-specific peptides early secretory antigenic target 6 (ESAT-6) and culture filtrate protein 10 (CFP-10), to determine the effect of LTBI treatment on these responses. Methods: 226 TB contacts with positive T-SPOT.TB results underwent repeat testing upon LTBI treatment completion. The majority (96%) received six 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 spot-forming cells (SFCs) / 2.5X105 peripheral blood mononuclear cells (PBMCs) pre and post treatment was 6 vs 4.5 for ESAT-6 (p=0.116) and 11 vs 4 for CFP-10 (p<0.001). There was a significant difference between the median falls with CFP-10 (6 SFCs / 2.5X105 PBMCs) and ESAT-6 (zero SFCs / 2.5X105 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 the 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, ESAT-6, CFP-10, interferon gamma responses, isoniazid




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