Skip to main content
Top
Published in: Respiratory Research 1/2007

Open Access 01-12-2007 | Research

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

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

Published in: Respiratory Research | Issue 1/2007

Login to get access

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.
Literature
1.
go back to reference World Health Organization: Global tuberculosis control. Surveillance planning, financing. WHO Report Geneva: World Health Organization 2005, 1–247. World Health Organization: Global tuberculosis control. Surveillance planning, financing. WHO Report Geneva: World Health Organization 2005, 1–247.
2.
go back to reference New framework for tuberculosis control and elimination in countries with a low incidenceEur Respir J 2002, 19:1–11. New framework for tuberculosis control and elimination in countries with a low incidenceEur Respir J 2002, 19:1–11.
3.
go back to reference Barnes PF: Diagnosing latent tuberculosis infection: turning glitter to gold. Am J Respir Crit Care Med 2004, 170:5–6.CrossRefPubMed Barnes PF: Diagnosing latent tuberculosis infection: turning glitter to gold. Am J Respir Crit Care Med 2004, 170:5–6.CrossRefPubMed
4.
go back to reference Behr MA, Wilson MA, Gill WP, Salamon H, Schoolnik GK, Rane S, Small PM: Comparative genomics of BCG vaccines by whole-genome DNA microarray. Science 1999, 284:1520–23.CrossRefPubMed Behr MA, Wilson MA, Gill WP, Salamon H, Schoolnik GK, Rane S, Small PM: Comparative genomics of BCG vaccines by whole-genome DNA microarray. Science 1999, 284:1520–23.CrossRefPubMed
5.
go back to reference Sorensen AL, Nagai S, Houen G, Andersen P, Andersen AB: Purification and characterization of a low-molecular-mass T-cell antigen secreted by Mycobacterium tuberculosis . Infect Immun 1995, 63:1710–17.PubMedPubMedCentral Sorensen AL, Nagai S, Houen G, Andersen P, Andersen AB: Purification and characterization of a low-molecular-mass T-cell antigen secreted by Mycobacterium tuberculosis . Infect Immun 1995, 63:1710–17.PubMedPubMedCentral
6.
go back to reference Pai M, Riley LW, Colford JM Jr: Interferon-gamma assays in the immunodiagnosis of tuberculosis: a systematic review. Lancet Inf Dis 2004, 4:761–76.CrossRef Pai M, Riley LW, Colford JM Jr: Interferon-gamma assays in the immunodiagnosis of tuberculosis: a systematic review. Lancet Inf Dis 2004, 4:761–76.CrossRef
7.
go back to reference Dheda K, Udwadia ZF, Huggett JF, Johnson MA, Rook GA: Utility of the antigen-specific interferon-gamma assay for the management of tuberculosis. Curr Opin Pulm Med 2005, 11:195–202.CrossRefPubMed Dheda K, Udwadia ZF, Huggett JF, Johnson MA, Rook GA: Utility of the antigen-specific interferon-gamma assay for the management of tuberculosis. Curr Opin Pulm Med 2005, 11:195–202.CrossRefPubMed
8.
go back to reference Ravn P, Demissie A, Equale T, Wondwosson H, Lein D, Amoundy HA, Mustafa AS, Jensen AK, Holm A, Rosenkrands I, Oftung F, Olobo J, Von Reyn F, Andersen P: Human T cell responses to the ESAT-6 antigen from Mycobacterium tuberculosis . J Infect Dis 1999, 179:637–45.CrossRefPubMed Ravn P, Demissie A, Equale T, Wondwosson H, Lein D, Amoundy HA, Mustafa AS, Jensen AK, Holm A, Rosenkrands I, Oftung F, Olobo J, Von Reyn F, Andersen P: Human T cell responses to the ESAT-6 antigen from Mycobacterium tuberculosis . J Infect Dis 1999, 179:637–45.CrossRefPubMed
9.
go back to reference Ulrichs T, Munk ME, Mollenkopf H, Behr-Perst S, Colangeli R, Gennaro ML, Kauffman SH: Differential T cell responses to Mycobacterium tuberculosis ESAT-6 in tuberculosis patients and healthy donors. Eur J Immunol 1998, 28:3949–58.CrossRefPubMed Ulrichs T, Munk ME, Mollenkopf H, Behr-Perst S, Colangeli R, Gennaro ML, Kauffman SH: Differential T cell responses to Mycobacterium tuberculosis ESAT-6 in tuberculosis patients and healthy donors. Eur J Immunol 1998, 28:3949–58.CrossRefPubMed
10.
go back to reference Doherty TM, Demissie A, Olobo J, Wolday D, Britton S, Equale T, Ravn P, Andersen P: Immune responses to the Mycobacterium tuberculosis -specific antigen ESAT-6 signal subclinical infection among contacts of tuberculosis patients. J Clin Microbiol 2002, 40:704–06.CrossRefPubMedPubMedCentral Doherty TM, Demissie A, Olobo J, Wolday D, Britton S, Equale T, Ravn P, Andersen P: Immune responses to the Mycobacterium tuberculosis -specific antigen ESAT-6 signal subclinical infection among contacts of tuberculosis patients. J Clin Microbiol 2002, 40:704–06.CrossRefPubMedPubMedCentral
11.
go back to reference Lalvani A, Pathan AA, Durkan H, Wilkinson KA, Whelan A, Deeks JJ, Reece WH, Latif M, Pasvol G, Hill AV: Enhanced contact tracing and spatial tracking of Mycobacterium tuberculosis infection by enumeration of antigen-specific T cells. Lancet 2001, 357:2017–21.CrossRefPubMed Lalvani A, Pathan AA, Durkan H, Wilkinson KA, Whelan A, Deeks JJ, Reece WH, Latif M, Pasvol G, Hill AV: Enhanced contact tracing and spatial tracking of Mycobacterium tuberculosis infection by enumeration of antigen-specific T cells. Lancet 2001, 357:2017–21.CrossRefPubMed
12.
go back to reference Mori T, Sakatani M, Yamagishi F: Specific Detection of Tuberculosis Infection with an Interferon-gamma-based assay using new antigens. AJRCCM 2004, 170:59–64. Mori T, Sakatani M, Yamagishi F: Specific Detection of Tuberculosis Infection with an Interferon-gamma-based assay using new antigens. AJRCCM 2004, 170:59–64.
13.
go back to reference Centers for Disease Control and Prevention: Guidelines for preventing the transmission of Mycobacterium tuberculosis in health-care settings. MMWR 2005, 54:1–141. Centers for Disease Control and Prevention: Guidelines for preventing the transmission of Mycobacterium tuberculosis in health-care settings. MMWR 2005, 54:1–141.
14.
go back to reference Vincenti D, Carrara S, De Mori P, Pucillo LP, Petrosillo N, Palmieri F, Armignacco O, Ippolito G, Girardi E, Amicosante M, Goletti D: Identification of ESAT-6 epitopes for the immunodiagnosis of active tuberculosis. Mol Med 2003, 19:105–11. Vincenti D, Carrara S, De Mori P, Pucillo LP, Petrosillo N, Palmieri F, Armignacco O, Ippolito G, Girardi E, Amicosante M, Goletti D: Identification of ESAT-6 epitopes for the immunodiagnosis of active tuberculosis. Mol Med 2003, 19:105–11.
15.
go back to reference Carrara S, Vincenti D, Petrosillo N, Amicosante M, Girardi E, Goletti D: Use of a T-cell-based assay for monitoring efficacy of anti-tuberculosis therapy. Clin Inf Dis 2004, 38:754–56.CrossRef Carrara S, Vincenti D, Petrosillo N, Amicosante M, Girardi E, Goletti D: Use of a T-cell-based assay for monitoring efficacy of anti-tuberculosis therapy. Clin Inf Dis 2004, 38:754–56.CrossRef
16.
go back to reference Goletti D, Vincenti D, Carrara S, Butera O, Bizzoni F, Bernardini G, Amicosante M, Girardi E: Selected RD1 peptides for active tuberculosis diagnosis: comparison of a gamma interferon whole-blood enzyme-linked immunosorbent assay and an enzyme-linked immunospot assay. Clin Diagn Lab Immunol 2005, 12:1311–16.PubMedPubMedCentral Goletti D, Vincenti D, Carrara S, Butera O, Bizzoni F, Bernardini G, Amicosante M, Girardi E: Selected RD1 peptides for active tuberculosis diagnosis: comparison of a gamma interferon whole-blood enzyme-linked immunosorbent assay and an enzyme-linked immunospot assay. Clin Diagn Lab Immunol 2005, 12:1311–16.PubMedPubMedCentral
17.
go back to reference Goletti D, Carrara S, Vincenti D, Saltini C, Busi Rizzi E, Schininà V, Ippolito G, Amicosante M, Girardi E: Accuracy of an immune diagnostic assay based on RD1 selected epitopes for active tuberculosis in a clinical setting: a pilot study. Clinical Microbiology and Infection 2006, 12:544–50.CrossRefPubMed Goletti D, Carrara S, Vincenti D, Saltini C, Busi Rizzi E, Schininà V, Ippolito G, Amicosante M, Girardi E: Accuracy of an immune diagnostic assay based on RD1 selected epitopes for active tuberculosis in a clinical setting: a pilot study. Clinical Microbiology and Infection 2006, 12:544–50.CrossRefPubMed
18.
go back to reference Goletti D, Butera O, Bizzoni F, Casetti R, Girardi E, Poccia F: RD1-specific memory CD4 T + cells correlates with favourable outcome of tuberculosis. JID 2006, 194:984–92.CrossRefPubMed Goletti D, Butera O, Bizzoni F, Casetti R, Girardi E, Poccia F: RD1-specific memory CD4 T + cells correlates with favourable outcome of tuberculosis. JID 2006, 194:984–92.CrossRefPubMed
19.
go back to reference Aiken AM, Hill PC, Fox A, McAdam KP, Jackson-Sillah D, Lugos MD, Donkor SA, Adegbola RA, Brookes RH: Reversion of the ELISPOT test after treatment in Gambian tuberculosis cases. BMC Infect Dis 2006, 6:66.CrossRefPubMedPubMedCentral Aiken AM, Hill PC, Fox A, McAdam KP, Jackson-Sillah D, Lugos MD, Donkor SA, Adegbola RA, Brookes RH: Reversion of the ELISPOT test after treatment in Gambian tuberculosis cases. BMC Infect Dis 2006, 6:66.CrossRefPubMedPubMedCentral
20.
go back to reference Lalvani A, Nagvenkar P, Udwadia Z, Pathan AA, Wilkinson KA, Shastri JS, Ewer K, Hill AV, Mehta A, Rodrigues C: Enumeration of T cells specific for RD1-encoded antigens suggests a high prevalence of latent Mycobacterium tuberculosis infection in healthy urban Indians. J Infect Dis 2001, 183:469–477.CrossRefPubMed Lalvani A, Nagvenkar P, Udwadia Z, Pathan AA, Wilkinson KA, Shastri JS, Ewer K, Hill AV, Mehta A, Rodrigues C: Enumeration of T cells specific for RD1-encoded antigens suggests a high prevalence of latent Mycobacterium tuberculosis infection in healthy urban Indians. J Infect Dis 2001, 183:469–477.CrossRefPubMed
21.
go back to reference Nicol MP, Pienaar D, Wood K, Eley B, Wilkinson RJ, Henderson H, Smith L, Samodien S, Beatty D: Enzyme-linked immunospot assay responses to early secretory antigenic target 6, culture filtrate protein 10, and purified protein derivative among children with tuberculosis: implications for diagnosis and monitoring of therapy. Clin Infect Dis 2005, 40:1301–8.CrossRefPubMed Nicol MP, Pienaar D, Wood K, Eley B, Wilkinson RJ, Henderson H, Smith L, Samodien S, Beatty D: Enzyme-linked immunospot assay responses to early secretory antigenic target 6, culture filtrate protein 10, and purified protein derivative among children with tuberculosis: implications for diagnosis and monitoring of therapy. Clin Infect Dis 2005, 40:1301–8.CrossRefPubMed
22.
go back to reference Chee CB, Khinmar KW, Gan SH, Barkham TM, Pushparani M, Wang YT: Latent Tuberculosis Infection Treatment and T-cell responses to M. tuberculosis-Specific Antigens. Am J Respir Crit Care Med 2006. doi:10.1164/rccm.200608–11090C. Chee CB, Khinmar KW, Gan SH, Barkham TM, Pushparani M, Wang YT: Latent Tuberculosis Infection Treatment and T-cell responses to M. tuberculosis-Specific Antigens. Am J Respir Crit Care Med 2006. doi:10.1164/rccm.200608–11090C.
23.
go back to reference Pai M, Joshi R, Dogra S, Pai M, Joshi R, Dogra S, Mendiratta DK, Narang P, Dheda K, Kalantri S: Persistently elevated T cell interferon-gamma responses after treatment for latent tuberculosis infection among health care workers in India: a preliminary report. Journal of Occupational Medicine and Toxicology 2006, 1:1–7.CrossRef Pai M, Joshi R, Dogra S, Pai M, Joshi R, Dogra S, Mendiratta DK, Narang P, Dheda K, Kalantri S: Persistently elevated T cell interferon-gamma responses after treatment for latent tuberculosis infection among health care workers in India: a preliminary report. Journal of Occupational Medicine and Toxicology 2006, 1:1–7.CrossRef
24.
go back to reference Wilkinson KA, Kon OM, Newton SM, Meintjes G, Davidson RN, Pasvol G, Wilkinson RJ: Effect of treatment of latent tuberculosis infection on the T cell response to Mycobacterium tuberculosis antigens. J Infect Dis 2006, 193:354–9.CrossRefPubMed Wilkinson KA, Kon OM, Newton SM, Meintjes G, Davidson RN, Pasvol G, Wilkinson RJ: Effect of treatment of latent tuberculosis infection on the T cell response to Mycobacterium tuberculosis antigens. J Infect Dis 2006, 193:354–9.CrossRefPubMed
25.
go back to reference Ewer K, Millington KA, Deeks JJ, Alvarez L, Bryant G, Lalvani A: Dynamic Antigen-specific T Cell Responses after Point-source Exposure to Mycobacterium tuberculosis. Am J Respir Crit Care Med 2006, 174:831–9.CrossRefPubMed Ewer K, Millington KA, Deeks JJ, Alvarez L, Bryant G, Lalvani A: Dynamic Antigen-specific T Cell Responses after Point-source Exposure to Mycobacterium tuberculosis. Am J Respir Crit Care Med 2006, 174:831–9.CrossRefPubMed
26.
go back to reference American Thoracic Society: Targeted tuberculin testing and treatment of latent tuberculosis infection. MMWR Morb Mortal Wkly Rep 2000, 49:1–51. American Thoracic Society: Targeted tuberculin testing and treatment of latent tuberculosis infection. MMWR Morb Mortal Wkly Rep 2000, 49:1–51.
27.
go back to reference Migliori GB, Hopewell PC, Blasi F, Spanevello A, Raviglione MC: Improving the TB case management: the international standards for tuberculosis care. Eur Respir J 2006, 28:687–90.CrossRefPubMed Migliori GB, Hopewell PC, Blasi F, Spanevello A, Raviglione MC: Improving the TB case management: the international standards for tuberculosis care. Eur Respir J 2006, 28:687–90.CrossRefPubMed
28.
go back to reference Wayne LG, Hayes LG: An in vitro model for sequential study of shiftdown of Mycobacterium tuberculosis through two stages of nonreplicating persistence. Infect Immun 1996, 64:2062–9.PubMedPubMedCentral Wayne LG, Hayes LG: An in vitro model for sequential study of shiftdown of Mycobacterium tuberculosis through two stages of nonreplicating persistence. Infect Immun 1996, 64:2062–9.PubMedPubMedCentral
29.
go back to reference Seder RA, Ahmed R: Similarities and differences in CD4+ and CD8+ effector and memory T cell generation. Nat Immunol 2003, 4:835–42.CrossRefPubMed Seder RA, Ahmed R: Similarities and differences in CD4+ and CD8+ effector and memory T cell generation. Nat Immunol 2003, 4:835–42.CrossRefPubMed
30.
go back to reference Pantaleo G, Harari A: Functional signatures in antiviral T-cell immunity for monitoring virus-associated diseases. Nat Rev Immunol 2006, 6:417–23.CrossRefPubMed Pantaleo G, Harari A: Functional signatures in antiviral T-cell immunity for monitoring virus-associated diseases. Nat Rev Immunol 2006, 6:417–23.CrossRefPubMed
31.
go back to reference Mollet L, Li TS, Samri A, Tournay C, Tubiana R, Calvez V, Debre P, Katlama C, Autran B: Dynamics of HIV-specific CD8 + T lymphocytes with changes in viral load. J Immunol 2000, 165:1692–04.CrossRefPubMed Mollet L, Li TS, Samri A, Tournay C, Tubiana R, Calvez V, Debre P, Katlama C, Autran B: Dynamics of HIV-specific CD8 + T lymphocytes with changes in viral load. J Immunol 2000, 165:1692–04.CrossRefPubMed
32.
go back to reference Godkin AJ, Thomas HC, Openshaw PJ: Evolution of Epitope-Specific Memory CD4-T Cells After Clearance of Hepatitis C Virus. J Immunol 2002, 169:2210–14.CrossRefPubMed Godkin AJ, Thomas HC, Openshaw PJ: Evolution of Epitope-Specific Memory CD4-T Cells After Clearance of Hepatitis C Virus. J Immunol 2002, 169:2210–14.CrossRefPubMed
33.
go back to reference Munoz-Elias EJ, Timm J, Botha T, Chan WT, Gomez JE, McKinney JD: Replication dynamics of Mycobacterium tuberculosis in chronically infected mice. Infect Immun 2005, 73:546–51.CrossRefPubMedPubMedCentral Munoz-Elias EJ, Timm J, Botha T, Chan WT, Gomez JE, McKinney JD: Replication dynamics of Mycobacterium tuberculosis in chronically infected mice. Infect Immun 2005, 73:546–51.CrossRefPubMedPubMedCentral
Metadata
Title
Isoniazid prophylaxis differently modulates T-cell responses to RD1-epitopes in contacts recently exposed to Mycobacterium tuberculosis: a pilot study
Authors
Delia Goletti
M Pasquale Parracino
Ornella Butera
Federica Bizzoni
Rita Casetti
Duilio Dainotto
Gianfranco Anzidei
Carla Nisii
Giuseppe Ippolito
Fabrizio Poccia
Enrico Girardi
Publication date
01-12-2007
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2007
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/1465-9921-8-5

Other articles of this Issue 1/2007

Respiratory Research 1/2007 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.