Research

Isoniazid prophylaxis differently modulates T-cell responses to RD1-epitopes in contacts recently exposed to Mycobacterium tuberculosis: a pilot study

Delia Goletti¹ , M Pasquale Parracino² , Ornella Butera¹ , Federica Bizzoni¹ , Rita Casetti³ , Duilio Dainotto⁴ , Gianfranco Anzidei⁵ , Carla Nisii⁶ , Giuseppe Ippolito⁶ , Fabrizio Poccia³ and Enrico Girardi²

¹  Translational Research Unit, Department of Experimental Research, Istituto Nazionale Malattie Infettive Lazzaro Spallanzani, IRCCS Rome, Italy

²  Clinical Epidemiology Unit, Department of Experimental Research, Istituto Nazionale Malattie Infettive Lazzaro Spallanzani, IRCCS Rome, Italy

³  Cellular Immunology Unit, Department of Experimental Research, Istituto Nazionale Malattie Infettive Lazzaro Spallanzani, IRCCS Rome, Italy

⁴  Presidio Interzonale di Pneumologia ASL Roma E, Rome, Italy

⁵  Pediatric Unit, Health Department, Istituto Nazionale Malattie Infettive Lazzaro Spallanzani, IRCCS Rome, Italy

⁶  Epidemiology Unit, Department of Experimental Research, Istituto Nazionale Malattie Infettive Lazzaro Spallanzani, IRCCS Rome, Italy

author email corresponding author email

Respiratory Research 2007, 8:5doi:10.1186/1465-9921-8-5

Published:	27 January 2007

Abstract

Rationale

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.

Methods and 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.

Conclusion

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.