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

Rina La Distia Nora, Ratna Sitompul, Marleen Bakker, Marjan A. Versnel, Sigrid M.A. Swagemakers, Peter J. van der Spek, Made Susiyanti, Lukman Edwar, Soedarman Sjamsoe, Gurmeet Singh, Raden Rara Diah Handayani, Aniki Rothova, P. Martin van Hagen, Willem A. Dik

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

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.

Original languageEnglish
Article numbere0206073
JournalPloS one
Volume13
Issue number10
DOIs
Publication statusPublished - 1 Oct 2018

Fingerprint Dive into the research topics of 'Type 1 interferon-inducible gene expression in QuantiFERON Gold TB-positive uveitis: A tool to stratify a high versus low risk of active tuberculosis?'. Together they form a unique fingerprint.

Cite this