Tear proteomic analysis in uveitis associated with behçet's disease: preliminary results

Introduction: Behçet’s disease (BD) is a multisystem inflammatory disorder with an incompletely understood pathogenesis. Ocular involvement occurs in 25–75% of patients and, if left untreated, may lead toblindness. The most common ocular manifestation is uveitis, typicallypresenting as bilateral, recurrent, and non-granulomatous panuveitis. In 10-year retrospective records of patients with Behçet’s uveitis,approximately one-third had severe visual impairment at onset, withnotable delays in diagnosis. Early and appropriate initiation of immunomodulatory treatment is essential. If uveitis development can bepredicted, treatment may be initiated earlier to prevent complications.However, no reliable biomarker currently exists to identify patients atrisk.Objectives: To identify potential protein biomarkers predictive of uveitis risk by analyzing proteomic alterations in tear samples of Behçet’spatients with and without uveitis.Methods: Fourteen Behçet’s patients (7 with uveitis, 7 without), followed in rheumatology clinics, were included. Tear samples were collected using Schirmer’s test paper and stored at –80°C. Tear proteinswere extracted and separated using Bradford and SDS-PAGE methods,followed by comparative analysis. Differentially expressed proteinswere excised from gels and analyzed via LC-MS/MS. Bioinformaticanalysis was conducted using the STRING database.Results: Proteomic analysis revealed 61 proteins with differentialexpression between the groups: 36 were upregulated and 25 downregulated in uveitis samples. Among the upregulated proteins,mucin-1, guanine nucleotide-binding protein, histone H1, and interalpha-trypsin inhibitor heavy chain showed the highest increases(up to 1000-fold). Other upregulated proteins exhibited 2–6.4-foldincreases. Among the downregulated proteins, ganglioside GM2 activator, immunoglobulin lambda, and V-type proton ATPase subunit G1demonstrated >1000-fold decreases, while the remainder had approximately 4-fold decreases. Bioinformatic analysis indicated that theseproteins are mainly involved in peptidase regulation, endopeptidaseinhibition, enzyme inhibition, and signaling pathways.Conclusion: Although it remains uncertain whether tear proteinexpression changes reflect disease pathogenesis or chronic inflammation, the identification of tear-based biomarkers may provide insightsinto uveitis development in Behçet’s disease. These findings may support earlier diagnosis and contribute to the development of targetedtherapies.