Proteomic Analysis of Autoimmune Retinopathy Implicates Neuronal Cell Adhesion Molecule as a Potential Biomarker

PURPOSE: To identify vitreous molecular biomarkers associated with autoimmune retinopathy (AIR). DESIGN: Case-control study. PARTICIPANTS: We analyzed 6 eyes from 4 patients diagnosed with AIR and 8 comparative controls diagnosed with idiopathic macular holes (IMHs) and epiretinal membranes (ERMs). METHODS: Vitreous biopsies were collected from the participants and analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) or multiplex enzyme-linked immunoassay (ELISA). MAIN OUTCOME MEASURES: Protein expression changes were evaluated by 1-way analysis of variance (significant P value < 0.05), hierarchical clustering, and pathway analysis to identify candidate protein biomarkers. RESULTS: There were 16 significantly upregulated and 17 significantly downregulated proteins in the vitreous of 3 patients with AIR compared with controls. The most significantly upregulated proteins included lysozyme C, zinc-alpha-2-glycoprotein, complement factor D, transforming growth factor-ß (TGF-ß)–induced protein, beta-crystallin B2, and alpha-crystallin A chain. The most significantly downregulated proteins included DIP2C, retbindin, and amyloid beta precursor-like protein 2. Pathway analysis revealed that vascular endothelial growth factor (VEGF) signaling was a top represented pathway in the vitreous of patients with AIR compared with controls. In comparison with a different cohort of 3 patients with AIR analyzed by multiplex ELISA, a commonly differentially expressed protein was neuronal cell adhesion molecule (NrCAM) with P values of 0.027 in the LC-MS/MS dataset and 0.035 in the ELISA dataset. CONCLUSIONS: Protein biomarkers in the vitreous, such as NrCAM, may eventually help diagnose AIR.