Abstract
PURPOSE: Nonanterior uveitis frequently involves the retinal vasculature; however, no molecular markers associated with the retinal vascular disease are currently known. In this study, we aimed to identify serum biomarker signatures associated with retinal vascular involvement in noninfectious pediatric uveitis. METHODS: We performed a 384-plex targeted proteomic analysis of serum samples of 154 noninfectious pediatric uveitis patients diagnosed with nonanterior uveitis (n = 74), idiopathic chronic anterior uveitis (iCAU, n = 36), or juvenile idiopathic arthritis-associated uveitis (JIA-U, n = 44), as well as 22 noninflammatory pediatric controls. Data on retinal vascular involvement (i.e., papillitis, cystoid macular edema, retinal vasculitis, or retinal capillary leakage on optical coherence tomography and/or fluorescein angiography) were used to stratify cases in the nonanterior uveitis group. RESULTS: In the analysis of nonanterior uveitis, we identified nine proteins significantly associated with retinal vascular involvement, including F13B, MYOM3, and PTPN9. These proteins were enriched through pathway enrichment analysis for the coagulation cascade. Comparing cases and controls, we identified 63 differentially expressed proteins, notably proteins involved in platelet biology and complement cascades, which could be primarily attributed to differences in serum proteomes between anterior uveitis and nonanterior uveitis groups. CONCLUSIONS: Serum proteins related to the coagulation and complement cascade are associated with retinal vascular involvement in pediatric uveitis patients. Our results indicate involvement of mediators that could interact with the microcirculation in pediatric uveitis and might serve as potential biomarkers in personalized medicine in the future. TRANSLATIONAL RELEVANCE: Our targeted proteomics analysis in serum of pediatric uveitis patients indicates involvement of mediators that could interact with the microcirculation in pediatric uveitis and might serve as potential biomarkers in personalized medicine in the future.