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

Goletti Delia, Parracino, Butera Ornella, Bizzoni Federica, Casetti Rita, Dainotto Duilio, Anzidei Gianfranco, Nisii Carla, Ippolito Giuseppe, Poccia Fabrizio, Girardi Enrico

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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.

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• Publié par: biomed
• Publié le: 01 janvier 2007
• Nombre de lectures: 72

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Respiratory Research

BioMedCentral

Open Access Research Isoniazid prophylaxis differently modulates T-cell responses to RD1-epitopes in contacts recently exposed toMycobacterium tuberculosis: a pilot study 1 21 1 Delia Goletti*, M Pasquale Parracino, Ornella Butera, Federica Bizzoni, 3 45 6 Rita Casetti, Duilio Dainotto, Gianfranco Anzidei, Carla Nisii, 6 32 Giuseppe Ippolito, Fabrizio Pocciaand Enrico Girardi

1 Address: TranslationalResearch Unit, Department of Experimental Research, Istituto Nazionale Malattie Infettive Lazzaro Spallanzani, IRCCS 2 Rome, Italy,Clinical Epidemiology Unit, Department of Experimental Research, Istituto Nazionale Malattie Infettive Lazzaro Spallanzani, IRCCS 3 Rome, Italy,Cellular Immunology Unit, Department of Experimental Research, Istituto Nazionale Malattie Infettive Lazzaro Spallanzani, IRCCS 4 5 Rome, Italy,Presidio Interzonale di Pneumologia ASL Roma E, Rome, Italy,Pediatric Unit, Health Department, Istituto Nazionale Malattie 6 Infettive Lazzaro Spallanzani, IRCCS Rome, Italy andEpidemiology Unit, Department of Experimental Research, Istituto Nazionale Malattie Infettive Lazzaro Spallanzani, IRCCS Rome, Italy Email: Delia Goletti*  [e-mail]; M Pasquale Parracino  [e-mail]; Ornella Butera  [e-mail]; Federica Bizzoni  [e-mail]; Rita Casetti  [e-mail]; Duilio Dainotto  [e-mail]; Gianfranco Anzidei  [e-mail]; Carla Nisii  [e-mail]; Giuseppe Ippolito  [e-mail]; Fabrizio Poccia  [e-mail]; Enrico Girardi  [e-mail] * Corresponding author

Published: 27 January 2007Received: 1 December 2006 Accepted: 27 January 2007 Respiratory Research2007,8:5 doi:10.1186/1465-9921-8-5 This article is available from: http://respiratory-research.com/content/8/1/5 © 2007 Goletti et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract Rationale:Existing data on the effect of treatment of latent tuberculosis infection (LTBI) on T-cell responses toMycobacterium 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.

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