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Type 1 interferon-inducible gene expression in QuantiFERON Gold TB-positive uveitis: A tool to stratify a high versus low risk of active tuberculosis?

QuantiFERON-Gold TB (QFT)-positive patients with undetermined cause of uveitis are problematic in terms of whether to diagnose and treat them for tuberculosis (TB). Here, we investigated whether peripheral blood expression of type 1 interferon (IFN)-inducible genes may be of use to stratify QFT-posi...

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Autores principales: La Distia Nora, Rina, Sitompul, Ratna, Bakker, Marleen, Versnel, Marjan A., Swagemakers, Sigrid M. A., van der Spek, Peter J., Susiyanti, Made, Edwar, Lukman, Sjamsoe, Soedarman, Singh, Gurmeet, Handayani, RR Diah, Rothova, Aniki, van Hagen, P. Martin, Dik, Willem A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6193765/
https://www.ncbi.nlm.nih.gov/pubmed/30336493
http://dx.doi.org/10.1371/journal.pone.0206073
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author La Distia Nora, Rina
Sitompul, Ratna
Bakker, Marleen
Versnel, Marjan A.
Swagemakers, Sigrid M. A.
van der Spek, Peter J.
Susiyanti, Made
Edwar, Lukman
Sjamsoe, Soedarman
Singh, Gurmeet
Handayani, RR Diah
Rothova, Aniki
van Hagen, P. Martin
Dik, Willem A.
author_facet La Distia Nora, Rina
Sitompul, Ratna
Bakker, Marleen
Versnel, Marjan A.
Swagemakers, Sigrid M. A.
van der Spek, Peter J.
Susiyanti, Made
Edwar, Lukman
Sjamsoe, Soedarman
Singh, Gurmeet
Handayani, RR Diah
Rothova, Aniki
van Hagen, P. Martin
Dik, Willem A.
author_sort La Distia Nora, Rina
collection PubMed
description QuantiFERON-Gold TB (QFT)-positive patients with undetermined cause of uveitis are problematic in terms of whether to diagnose and treat them for tuberculosis (TB). Here, we investigated whether peripheral blood expression of type 1 interferon (IFN)-inducible genes may be of use to stratify QFT-positive patients with uveitis into groups of high versus low risk of having active TB-associated uveitis. We recruited all new uveitis patients in Cipto Mangunkusumo Hospital, Jakarta, Indonesia for one year. We included 12 patients with uveitis and clinically diagnosed active pulmonary TB, 58 QFT-positive patients with uveitis of unknown cause, 10 newly diagnosed sputum-positive active pulmonary TB patients without uveitis and 23 QFT-negative healthy controls. Expression of 35 type 1 IFN-inducible genes was measured in peripheral blood cells from active pulmonary TB patients without uveitis and healthy controls. Differentially expressed genes were identified and used for further clustering analyses of the uveitis groups. A type-1 IFN gene signature score was calculated and the optimal cut-off value for this score to differentiate active pulmonary TB from healthy controls was determined and applied to QFT-positive patients with uveitis of unknown cause. Ten type 1 IFN-inducible genes were differentially expressed between active pulmonary TB and healthy controls. Expression of these 10 genes in QFT-positive patients with uveitis of unknown cause revealed three groups: 1); patients resembling active pulmonary TB, 2); patients resembling healthy controls, and 3); patients displaying an in-between gene expression pattern. A type 1 IFN gene signature score ≥5.61 displayed high sensitivity (100%) and specificity (91%) for identification of active TB. Application of this score to QFT-positive patients with uveitis of unknown cause yielded two groups with expected different likelihood (high vs. low) of having active-TB uveitis, and therefore may be useful in clinical management decisions.
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spelling pubmed-61937652018-11-05 Type 1 interferon-inducible gene expression in QuantiFERON Gold TB-positive uveitis: A tool to stratify a high versus low risk of active tuberculosis? La Distia Nora, Rina Sitompul, Ratna Bakker, Marleen Versnel, Marjan A. Swagemakers, Sigrid M. A. van der Spek, Peter J. Susiyanti, Made Edwar, Lukman Sjamsoe, Soedarman Singh, Gurmeet Handayani, RR Diah Rothova, Aniki van Hagen, P. Martin Dik, Willem A. PLoS One Research Article QuantiFERON-Gold TB (QFT)-positive patients with undetermined cause of uveitis are problematic in terms of whether to diagnose and treat them for tuberculosis (TB). Here, we investigated whether peripheral blood expression of type 1 interferon (IFN)-inducible genes may be of use to stratify QFT-positive patients with uveitis into groups of high versus low risk of having active TB-associated uveitis. We recruited all new uveitis patients in Cipto Mangunkusumo Hospital, Jakarta, Indonesia for one year. We included 12 patients with uveitis and clinically diagnosed active pulmonary TB, 58 QFT-positive patients with uveitis of unknown cause, 10 newly diagnosed sputum-positive active pulmonary TB patients without uveitis and 23 QFT-negative healthy controls. Expression of 35 type 1 IFN-inducible genes was measured in peripheral blood cells from active pulmonary TB patients without uveitis and healthy controls. Differentially expressed genes were identified and used for further clustering analyses of the uveitis groups. A type-1 IFN gene signature score was calculated and the optimal cut-off value for this score to differentiate active pulmonary TB from healthy controls was determined and applied to QFT-positive patients with uveitis of unknown cause. Ten type 1 IFN-inducible genes were differentially expressed between active pulmonary TB and healthy controls. Expression of these 10 genes in QFT-positive patients with uveitis of unknown cause revealed three groups: 1); patients resembling active pulmonary TB, 2); patients resembling healthy controls, and 3); patients displaying an in-between gene expression pattern. A type 1 IFN gene signature score ≥5.61 displayed high sensitivity (100%) and specificity (91%) for identification of active TB. Application of this score to QFT-positive patients with uveitis of unknown cause yielded two groups with expected different likelihood (high vs. low) of having active-TB uveitis, and therefore may be useful in clinical management decisions. Public Library of Science 2018-10-18 /pmc/articles/PMC6193765/ /pubmed/30336493 http://dx.doi.org/10.1371/journal.pone.0206073 Text en © 2018 La Distia Nora 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 (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
La Distia Nora, Rina
Sitompul, Ratna
Bakker, Marleen
Versnel, Marjan A.
Swagemakers, Sigrid M. A.
van der Spek, Peter J.
Susiyanti, Made
Edwar, Lukman
Sjamsoe, Soedarman
Singh, Gurmeet
Handayani, RR Diah
Rothova, Aniki
van Hagen, P. Martin
Dik, Willem A.
Type 1 interferon-inducible gene expression in QuantiFERON Gold TB-positive uveitis: A tool to stratify a high versus low risk of active tuberculosis?
title Type 1 interferon-inducible gene expression in QuantiFERON Gold TB-positive uveitis: A tool to stratify a high versus low risk of active tuberculosis?
title_full Type 1 interferon-inducible gene expression in QuantiFERON Gold TB-positive uveitis: A tool to stratify a high versus low risk of active tuberculosis?
title_fullStr Type 1 interferon-inducible gene expression in QuantiFERON Gold TB-positive uveitis: A tool to stratify a high versus low risk of active tuberculosis?
title_full_unstemmed Type 1 interferon-inducible gene expression in QuantiFERON Gold TB-positive uveitis: A tool to stratify a high versus low risk of active tuberculosis?
title_short Type 1 interferon-inducible gene expression in QuantiFERON Gold TB-positive uveitis: A tool to stratify a high versus low risk of active tuberculosis?
title_sort type 1 interferon-inducible gene expression in quantiferon gold tb-positive uveitis: a tool to stratify a high versus low risk of active tuberculosis?
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6193765/
https://www.ncbi.nlm.nih.gov/pubmed/30336493
http://dx.doi.org/10.1371/journal.pone.0206073
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