Can interferon‑inducible gene expression guide treatment? A prospective study in QuantiFERON‑positive uveitis with undetermined cause

PURPOSE: The purpose of this study was to evaluate the utility of baseline interferon (IFN)‑inducible gene expression as a prognostic biomarker for Anti‑tubercular therapy (ATT) response in patients with undetermined cause of uveitis who tested positive for QuantiFERON‑TB Gold (QFT‑positive uveitis). METHODS: This prospective cohort study included 17 QFT‑positive uveitis patients at a tertiary uveitis center in Indonesia. Baseline and week 2 peripheral blood transcripts were evaluated through real time‑quantitative polymerase chain reaction to assess the expression of 10 IFN‑inducible genes (IRF7, IFIT2, STAT1, IL1B, MyD88, TLR8, FCGR1B, GBP1, UBE2L6, and SERPING1). Patients were stratified into clusters based on gene expression patterns. The primary outcome was complete resolution of uveitis at 6 months. RESULTS: Hierarchical clustering revealed two distinct groups. Patients with higher baseline expression of IFN genes (Cluster 2) were more likely to achieve complete uveitis resolution after ATT compared to those with lower expression levels (Cluster 1) (80% vs. 43%). Using a previously established IFN gene signature score (IGSS) cutoff (≥5.61), 82% of high‑scoring patients showed complete resolution, compared to only 33% in the low‑scoring group (P = 0.046). However, week 2 gene expression changes did not correlate with treatment response, indicating limited utility in monitoring disease activity or predicting long‑term outcomes. CONCLUSION: Baseline, but not week 2, peripheral blood IFN‑inducible gene expression may serve as a prognostic biomarker for stratifying QFT‑positive uveitis patients through prediction of their response to treatment. Patients with higher baseline IGSS are more likely to require ATT to achieve uveitis resolution at 6‑month follow‑up.