title: Latent tuberculosis infection treatment and T-cell responses to Mycobacterium tuberculosis-specific antigens.
abstract: 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.
authors.affiliation: Singapore Tuberculosis Control Unit, Department of Clinical Epidemiology, Tan Tock Seng Hospital, Singapore, Singapore. cynthia_chee@ttsh.com.sg
authors.forename: Cynthia B E
authors.initials: CB
authors.lastname: Chee
authors.forename: Kyi W
authors.initials: KW
authors.lastname: KhinMar
authors.forename: Suay H
authors.initials: SH
authors.lastname: Gan
authors.forename: Timothy M S
authors.initials: TM
authors.lastname: Barkham
authors.forename: Mariappan
authors.initials: M
authors.lastname: Pushparani
authors.forename: Yee T
authors.initials: YT
authors.lastname: Wang
mesh_terms: 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
chemical_list: 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