Novel M tuberculosis antigen-specific T-cells are early markers of infection and disease progression.
BACKGROUND
Mycobacterium tuberculosis Region-of-Difference-1 gene products present opportunities for specific diagnosis of M. tuberculosis infection, yet immune responses to only two gene-products, Early Secretory Antigenic Target-6 (ESAT-6) and Culture Filtrate Protein-10 (CFP-10), have been comprehensively investigated.


METHODS
T-cell responses to Rv3873, Rv3878 and Rv3879c were quantified by IFN-γ-enzyme-linked-immunospot (ELISpot) in 846 children with recent household tuberculosis exposure and correlated with kinetics of tuberculin skin test (TST) and ESAT-6/CFP-10-ELISpot conversion over six months and clinical outcome over two years.


RESULTS
Responses to Rv3873, Rv3878, and Rv3879c were present in 20-25% of contacts at enrolment. Rv3873 and Rv3879c responses were associated with and preceded TST conversion (P=0.02 and P=0.04 respectively), identifying these antigens as early targets of cell-mediated immunity following M. tuberculosis exposure. Responses to Rv3873 were additionally associated with subsequent ESAT-6/CFP-10-ELISpot conversion (P=0.04). Responses to Rv3873 and Rv3878 predicted progression to active disease (adjusted incidence rate ratio [95% CI] 3.06 [1.05,8.95; P=0.04], and 3.32 [1.14,9.71; P=0.03], respectively). Presence of a BCG-vaccination scar was associated with a 67% (P=0.03) relative risk reduction for progression to active tuberculosis.


CONCLUSIONS
These RD1-derived antigens are early targets of cellular immunity following tuberculosis exposure and T-cells specific for these antigens predict progression to active tuberculosis suggesting diagnostic and prognostic utility.
Tuberculosis Research Unit, Department of Respiratory Medicine, National Heart and Lung Institute, Imperial College London, London, United Kingdom.
Davinder P S
DP
Dosanjh
Mustafa
M
Bakir
Kerry A
KA
Millington
Ahmet
A
Soysal
Yasemin
Y
Aslan
Serpil
S
Efee
Jonathan J
JJ
Deeks
Ajit
A
Lalvani
D000942:Antigens, Bacterial / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014374:Tuberculin Test
D000942:Antigens, Bacterial; D016056:Immunodominant Epitopes; D007371:Interferon-gamma