T-SPOT.TB responses during treatment of pulmonary tuberculosis.
BACKGROUND
Immune responses to Mycobacterium tuberculosis antigens could serve as surrogate markers of treatment response.


METHODS
Using the T-SPOT.TB assay and frozen peripheral blood mononuclear cells, we enumerated ESAT-6- and CFP-10-specific IFN-gamma-producing T cells over time in pulmonary TB patients receiving directly observed treatment. T cell responses (measured as "spot forming cells" or "SFCs") were assessed prior to treatment and at 16 and 24 weeks of treatment.


RESULTS
58 patients were evaluated, of whom 57 were HIV seronegative. Mean (SD) ESAT-6, CFP-10, and summed RD1 specific SFCs declined from 42.7 (72.7), 41.2 (66.4), and 83.8 (105.7) at baseline to 23.3 (39.4, p = 0.01), 23.2 (29.4, p = 0.18), and 46.5 (59.5, p = 0.02) at completion of 24 weeks of treatment, respectively. Only 10% of individuals with a baseline reactive test reverted to negative at treatment week 24. For the group that was culture positive at completion of 8 weeks of treatment compared to the culture negative group, the incidence rate ratio (IRR) of ESAT-6, CFP-10, and summed RD1 specific SFC counts were, respectively, 2.23 (p = 0.048), 1.51 (p = 0.20), and 1.83 (p = 0.047). Patients with cavitary disease had mean ESAT-6 specific SFC counts that were higher than those without cavitary disease (IRR 2.08, p = 0.034).


CONCLUSIONS
IFN-gamma-producing RD1-specific T cells, as measured in the T-SPOT.TB assay, may be directly related to bacterial load in patients undergoing treatment for pulmonary TB. However, high inter-subject variability in quantitative results coupled with failure of reversion to negative of qualitative results in most subjects at treatment completion may limit the utility of this assay as a surrogate marker for treatment efficacy.
Ribeiro
Samantha
S
Instituto de Doenças do Torax/Hospital Clementino Fraga Filho/Universidade Federal do Rio de Janeiro, Brazil. sbrmicroimuno@yahoo.com.br
Dooley
Kelly
K
Hackman
Judith
J
Loredo
Carla
C
Efron
Anne
A
Chaisson
Richard E
RE
Conde
Marcus B
MB
Boechat
Neio
N
Dorman
Susan E
SE
D000328:Adult; D000942:Antigens, Bacterial / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism; D002452:Cell Count; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008137:Longitudinal Studies; D008297:Male; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D011237:Predictive Value of Tests; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016896:Treatment Outcome; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy* / Q000276:immunology; D055815:Young Adult
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D007371:Interferon-gamma