Serum Proteomic Analysis Identifies Junction Plakoglobin and Glyceraldehyde-3-Phosphate Dehydrogenase as Potential Novel Circulating Biomarkers for Patients with Multiple Sclerosis.

Multiple sclerosis (MS) is a neurological condition characterized by recurrent inflammation, demyelination, axonal injury, and functional impairment. MS has a diverse array of clinical manifestations, with the progressive variants leading to neurological impairment. Sensitive and accurate biomarkers are required to diagnose, predict disease progression, and guide MS management. Here, we utilized liquid chromatography-mass spectrometry-based proteomics (LC-MS/MS) to find biomarkers in serum from patients with MS. The study examined protein expression in healthy individuals (n = 20) and MS groups (n = 60), comprising 20 patients in each disease course (relapsing-remitting (RRMS), primary progressive (PPMS), and secondary progressive (SPMS)). An enzyme-linked immunosorbent assay (ELISA) was used to verify a candidate protein in serum samples from patients with MS (n = 18) and healthy controls (HC) (n = 15) (validation cohort). Our findings showed 12 differentially expressed proteins (DEPs). Among the discovered proteins, some have been previously documented in MS, while others constitute novel findings. We found two proteins, junction plakoglobin (JUP) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), that were downregulated and upregulated in patients with MS relative to HCs, respectively. ELISA validations were consistent with those from LC-MS/MS. Identification of these proteins may help elucidate pathogenic processes and support novel therapeutic methods for MS.