Latent tuberculosis infection treatment and T-cell responses to Mycobacterium tuberculosis-specific antigens.
BACKGROUND
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 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.


CONCLUSIONS
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.
Chee
Cynthia B E
CB
Singapore Tuberculosis Control Unit, Department of Clinical Epidemiology, Tan Tock Seng Hospital, Singapore, Singapore. cynthia_chee@ttsh.com.sg
KhinMar
Kyi W
KW
Gan
Suay H
SH
Barkham
Timothy M S
TM
Pushparani
Mariappan
M
Wang
Yee T
YT
D000293:Adolescent; D000328:Adult; D000368:Aged; D000942:Antigens, Bacterial / Q000187:drug effects* / Q000276:immunology / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000276:immunology / Q000494:pharmacology*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007118:Immunoassay; D007371:Interferon-gamma / Q000032:analysis / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis; D010455:Peptides / Q000276:immunology / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D016896:Treatment Outcome; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy* / Q000276:immunology
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C117940:CFP-10 protein, Mycobacterium tuberculosis; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D010455:Peptides; C072681:Mycobacterium tuberculosis antigens; D007371:Interferon-gamma