Improving T-Cell Assays for the Diagnosis of Latent TB Infection: Potential of a Diagnostic Test Based on IP-10

BACKGROUND: There is a need for simple tools such as the M.tuberculosis specific IFN-γ release assays (IGRA) to improve diagnosis of M.tuberculosis-infection in children. The aim of the study was to evaluate the performance of an IP-10 and IL-2 based tests for the diagnosis of M.tuberculosis-infecti...

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Autores principales: Ruhwald, Morten, Petersen, Janne, Kofoed, Kristian, Nakaoka, Hiroshi, Cuevas, Luis Eduardo, Lawson, Lovett, Squire, Stephen Bertil, Eugen-Olsen, Jesper, Ravn, Pernille
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2483344/
https://www.ncbi.nlm.nih.gov/pubmed/18682747
http://dx.doi.org/10.1371/journal.pone.0002858
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author Ruhwald, Morten
Petersen, Janne
Kofoed, Kristian
Nakaoka, Hiroshi
Cuevas, Luis Eduardo
Lawson, Lovett
Squire, Stephen Bertil
Eugen-Olsen, Jesper
Ravn, Pernille
author_facet Ruhwald, Morten
Petersen, Janne
Kofoed, Kristian
Nakaoka, Hiroshi
Cuevas, Luis Eduardo
Lawson, Lovett
Squire, Stephen Bertil
Eugen-Olsen, Jesper
Ravn, Pernille
author_sort Ruhwald, Morten
collection PubMed
description BACKGROUND: There is a need for simple tools such as the M.tuberculosis specific IFN-γ release assays (IGRA) to improve diagnosis of M.tuberculosis-infection in children. The aim of the study was to evaluate the performance of an IP-10 and IL-2 based tests for the diagnosis of M.tuberculosis-infection in recently exposed children from Nigeria. METHODOLOGY AND PRINCIPAL FINDINGS: Samples were obtained from 59 children at high risk of infection with M.tuberculosis (contacts of adults with smear and culture-positive tuberculosis) and 61 at low risk (contacts of smear-negative/culture-positive tuberculosis or community controls). IP-10 and IL-2 was measured in plasma after stimulation of whole-blood with M.tuberculosis specific antigens and mitogen. Previously developed criteria for positive IP-10 and IL-2 tests were used and the diagnostic performances of the IP-10 and IL-2 tests were compared with the Quantiferon In-Tube (QFT-IT) and the Tuberculin Skin Tests (TST). In response to M.tuberculosis specific antigens, the high-risk children expressed significantly higher levels of IP-10 (1358 pg/ml[IQR 278–2535 pg/ml]) and IL-2 (164 pg/ml[11–590 pg/ml]) than low risk groups 149 pg/ml(25–497 pg/ml), and 0 pg/ml(0–3 pg/ml), respectively. There was excellent agreement (>89%,k>0.80) between IP-10, IL-2 tests and QFT-IT, better than with TST (>74%,k>0.49). The IP-10 and IL-2 responses were strongly associated with M.tuberculosis exposure and with grade of infectiousness of the index cases (p<0.0001). IP-10, IL-2, and TST but not QFT-IT was associated with age of the child in the low risk groups (p<0.02). CONCLUSIONS/SIGNIFICANCE: IP-10 is expressed in high levels and results of the IP-10 test were comparable to the QFT-IT. IL-2 was released in low amounts in response to the antigens and not in response to the mitogen therefore IL-2 seems a less useful marker. We have demonstrated that IP-10 and possibly IL-2 could be alternative or adjunct markers to IFN-γ in the diagnosis infection with M.tuberculosis.
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spelling pubmed-24833442008-08-06 Improving T-Cell Assays for the Diagnosis of Latent TB Infection: Potential of a Diagnostic Test Based on IP-10 Ruhwald, Morten Petersen, Janne Kofoed, Kristian Nakaoka, Hiroshi Cuevas, Luis Eduardo Lawson, Lovett Squire, Stephen Bertil Eugen-Olsen, Jesper Ravn, Pernille PLoS One Research Article BACKGROUND: There is a need for simple tools such as the M.tuberculosis specific IFN-γ release assays (IGRA) to improve diagnosis of M.tuberculosis-infection in children. The aim of the study was to evaluate the performance of an IP-10 and IL-2 based tests for the diagnosis of M.tuberculosis-infection in recently exposed children from Nigeria. METHODOLOGY AND PRINCIPAL FINDINGS: Samples were obtained from 59 children at high risk of infection with M.tuberculosis (contacts of adults with smear and culture-positive tuberculosis) and 61 at low risk (contacts of smear-negative/culture-positive tuberculosis or community controls). IP-10 and IL-2 was measured in plasma after stimulation of whole-blood with M.tuberculosis specific antigens and mitogen. Previously developed criteria for positive IP-10 and IL-2 tests were used and the diagnostic performances of the IP-10 and IL-2 tests were compared with the Quantiferon In-Tube (QFT-IT) and the Tuberculin Skin Tests (TST). In response to M.tuberculosis specific antigens, the high-risk children expressed significantly higher levels of IP-10 (1358 pg/ml[IQR 278–2535 pg/ml]) and IL-2 (164 pg/ml[11–590 pg/ml]) than low risk groups 149 pg/ml(25–497 pg/ml), and 0 pg/ml(0–3 pg/ml), respectively. There was excellent agreement (>89%,k>0.80) between IP-10, IL-2 tests and QFT-IT, better than with TST (>74%,k>0.49). The IP-10 and IL-2 responses were strongly associated with M.tuberculosis exposure and with grade of infectiousness of the index cases (p<0.0001). IP-10, IL-2, and TST but not QFT-IT was associated with age of the child in the low risk groups (p<0.02). CONCLUSIONS/SIGNIFICANCE: IP-10 is expressed in high levels and results of the IP-10 test were comparable to the QFT-IT. IL-2 was released in low amounts in response to the antigens and not in response to the mitogen therefore IL-2 seems a less useful marker. We have demonstrated that IP-10 and possibly IL-2 could be alternative or adjunct markers to IFN-γ in the diagnosis infection with M.tuberculosis. Public Library of Science 2008-08-06 /pmc/articles/PMC2483344/ /pubmed/18682747 http://dx.doi.org/10.1371/journal.pone.0002858 Text en Ruhwald et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Ruhwald, Morten
Petersen, Janne
Kofoed, Kristian
Nakaoka, Hiroshi
Cuevas, Luis Eduardo
Lawson, Lovett
Squire, Stephen Bertil
Eugen-Olsen, Jesper
Ravn, Pernille
Improving T-Cell Assays for the Diagnosis of Latent TB Infection: Potential of a Diagnostic Test Based on IP-10
title Improving T-Cell Assays for the Diagnosis of Latent TB Infection: Potential of a Diagnostic Test Based on IP-10
title_full Improving T-Cell Assays for the Diagnosis of Latent TB Infection: Potential of a Diagnostic Test Based on IP-10
title_fullStr Improving T-Cell Assays for the Diagnosis of Latent TB Infection: Potential of a Diagnostic Test Based on IP-10
title_full_unstemmed Improving T-Cell Assays for the Diagnosis of Latent TB Infection: Potential of a Diagnostic Test Based on IP-10
title_short Improving T-Cell Assays for the Diagnosis of Latent TB Infection: Potential of a Diagnostic Test Based on IP-10
title_sort improving t-cell assays for the diagnosis of latent tb infection: potential of a diagnostic test based on ip-10
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2483344/
https://www.ncbi.nlm.nih.gov/pubmed/18682747
http://dx.doi.org/10.1371/journal.pone.0002858
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