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.
Highlights
Tuberculosis (TB) is one of the major health problems worldwide
We explore whether the expression of type 1 IFN-inducible genes in peripheral blood cells from patients with QuantiFERON Gold TB (QFT)-positive uveitis can serve as a tool to stratify these patients into groups with a high or low likelihood of having active TB uveitis
The post hoc analysis revealed that the healthy controls were significantly younger than the QFT-positive group with uveitis of unknown origin (p
Summary
Tuberculosis (TB) is one of the major health problems worldwide. TB-associated uveitis represents a major cause of infectious uveitis in Indonesia and in other countries endemic for TB. [1,2,3,4,5] The diagnosis of TB uveitis is mainly based on microbiological proof of active TB infection in the eye or a positive culture in other organs, most frequently the lungs. The diagnosis TB uveitis is challenging in the absence of clinically apparent pulmonary disease because ocular tissue examinations are not readily available and biopsies are troublesome to perform.[6]. The advent of the IFN-γ release assay (IGRA) or QuantiFERON Gold TB (QFT) test enabled the identification of individuals with a prior Mycobacterium tuberculosis (Mtb) infection. The QFT test provides evidence of an immune response to Mtb, it lacks the specificity to distinguish between active and latent TB.[7] Whether QFT-positive uveitis is the result of a direct infection of the retina, an anti-retinal immune response in QFT-positive individuals or a combination of both is unclear.[8] using QFT as a diagnostic test for active TB is not feasible in cases suspect of active TB uveitis
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