Isoniazid prophylaxis differently modulates T-cell responses to RD1-epitopes in contacts recently exposed to Mycobacterium tuberculosis: a pilot study.
BACKGROUND
Existing data on the effect of treatment of latent tuberculosis infection (LTBI) on T-cell responses to Mycobacterium tuberculosis (MTB)-specific antigens are contradictory. Differences in technical aspects of the assays used to detect this response and populations studied might explain some of these discrepancies. In an attempt to find surrogate markers of the effect of LTBI treatment, it would be important to determine whether, among contacts of patients with contagious tuberculosis, therapy for LTBI could cause changes in MTB-specific immune responses to a variety of RD1-antigens.


RESULTS
In a longitudinal study, 44 tuberculin skin test+ recent contacts were followed over a 6-month period and divided according to previous exposure to MTB and LTBI treatment. The following tests which evaluate IFN-gamma responses to RD1 antigens were performed: QuantiFERON TB Gold, RD1 intact protein- and selected peptide-based assays. Among the 24 contacts without previous exposure that completed therapy, we showed a significant decrease of IFN-gamma response in all tests employed. The response to RD1 selected peptides was found to be more markedly decreased compared to that to other RD1 antigens. Conversely, no significant changes in the response to RD1 reagents were found in 9 treated subjects with a known previous exposure to MTB and in 11 untreated controls.


CONCLUSIONS
These data suggest that the effect of INH prophylaxis on RD1-specific T-cell responses may be different based on the population of subjects enrolled (recent infection versus re-infection) and, to a minor extent, on the reagents used.
Goletti
Delia
D
Translational Research Unit, Department of Experimental Research, Istituto Nazionale Malattie Infettive Lazzaro Spallanzani, IRCCS Rome, Italy. d.goletti@tiscali.it
Parracino
M Pasquale
MP
Butera
Ornella
O
Bizzoni
Federica
F
Casetti
Rita
R
Dainotto
Duilio
D
Anzidei
Gianfranco
G
Nisii
Carla
C
Ippolito
Giuseppe
G
Poccia
Fabrizio
F
Girardi
Enrico
E
D000328:Adult; D019072:Antibiotic Prophylaxis / Q000379:methods; D000942:Antigens, Bacterial / Q000276:immunology*; D000939:Epitopes / Q000276:immunology*; D005260:Female; D006801:Humans; D007538:Isoniazid / Q000494:pharmacology* / Q000627:therapeutic use; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000276:immunology; D010865:Pilot Projects; D011446:Prospective Studies; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D014374:Tuberculin Test; D014376:Tuberculosis / Q000188:drug therapy / Q000276:immunology
D000942:Antigens, Bacterial; D000939:Epitopes; C072681:Mycobacterium tuberculosis antigens; D007538:Isoniazid