Abstract
BackgroundTo identify candidate tear fluid biomarkers in patients with unilateral acute anterior uveitis (AAU) that can aid in the differentiation between these patients and patients with bacterial keratitis or healthy controls.MethodsThirteen patients (40.1 ± 16.2 years of age) with unilateral AAU, seven patients with unilateral bacterial keratitis (40.2 ± 15.3 years of age), and 14 healthy subjects (41.1 ± 11.6 years of age) were included. The tear proteome of affected eyes was compared with that of the unaffected eye or healthy controls. Proteins were identified by liquid chromatography tandem mass spectrometry and enzyme-linked immunosorbent assay.ResultsRelative protein ratios were detected and calculated for 272 unique proteins. Compared with healthy controls and the unaffected eye, the top upregulated proteins in AAU eyes were submaxillary gland androgen regulated protein 3B (SMR3B) and SMR3A. Similarly, the top upregulated proteins in bacterial keratitis were S100 calcium-binding protein A9 and orosomucoid 2. The acute phase response protein Serpin Family A Member 3 (SERPINA3) was increased in the healthy eye of AAU patients (P = 0.019) compared with healthy controls. Laser flare measurements in affected eyes of AAU patients showed positive logarithmic correlation with SERPINA3 in tear samples of the unaffected eye (P = 0.022). The use of SERPINA3 as a tear biomarker yielded a sensitivity of 85% and a specificity of 71% in detecting patients with AAU in the study population.ConclusionsThe acute phase response protein SERPINA3 was increased in tear samples of unaffected eyes of patients with unilateral AAU compared with healthy controls. This study highlights SERPINA3 as a potential biomarker for AAU. Future research should explore the dynamic properties of SERPINA3 in the tear fluid of active and quiescent uveitis eyes.
Highlights
To identify candidate tear fluid biomarkers in patients with unilateral acute anterior uveitis (AAU) that can aid in the differentiation between these patients and patients with bacterial keratitis or healthy controls
Since the concentration of SERPINA3 in the unaffected eye of AAU patients was significantly higher than in the eyes of healthy controls, we explored to which extent the measurement of SERPINA3 could be used as a biomarker for unilateral AAU
The current study demonstrated an increased concentration of SERPINA3 by enzyme-linked immunosorbent assay (ELISA) in tear fluid of the unaffected eyes of patients with unilateral AAU compared with healthy controls
Summary
To identify candidate tear fluid biomarkers in patients with unilateral acute anterior uveitis (AAU) that can aid in the differentiation between these patients and patients with bacterial keratitis or healthy controls. AAU and bacterial keratitis are both common and potentially sight threatening, and such patients need urgent referral to an ophthalmologist for management. Symptoms and signs of AAU or bacterial keratitis may be misinterpreted as non-sight threatening external eye disease, delaying necessary referral to ophthalmologists. There are relatively few studies on tear fluid biomarkers in uveitis [4, 7, 19, 22], but novel biomarkers were recently suggested for Behcet’s disease and acute, non-infectious uveitis [18, 25]. Definite tear biomarkers for uveitis are yet to be established
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