Proteome analysis of biomarkers in the cerebrospinal fluid of neuromyelitis optica patients

Purpose: To better understand the pathophysiological mechanisms underlying neuromyelitis optica (NMO), we developed a proteomics platform for biomarker discovery in the cerebrospinal fluid (CSF) of patients with NMO. Methods: Two-dimensional electrophoresis (2-DE) and matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS) were used to compare the CSF proteome of NMO patients with that of controls. A subsequent ELISA and western blot analysis were performed to verify the results of the proteomic analysis. Pathway Studio 5.0 software was used to determine possible functional interactions among these differentially expressed proteins. Results: Using 2-DE and MALDI-TOF MS, we identified 11 differentially expressed proteins and two isoforms of these same proteins. The expression of four proteins was enhanced, whereas the expression of seven proteins was reduced in the NMO group in comparison to the control group. These differences in protein expression were confirmed by performing ELISA and western blot analyses (p<0.01). Protein network analyses revealed biologic interactions and cross-talks among these differentially expressed proteins. Conclusions: Because of their unique expression profile in NMO CSFs, these proteins are candidate biomarkers for NMO. Thus, our findings may have important implications for both the diagnosis of NMO and the further understanding of its pathogenesis. Neuromyelitis optica (NMO), also termed Devic's syndrome, is an idiopathic inflammatory demyelinating disease of the central nervous system (CNS) predominantly affecting optic nerves and the spinal cord [1]. It is a disabling and, occasionally, life-threatening disease. Patients with NMO can experience relapses of optic neuritis or myelitis that occur in intervals of months or years. NMO is considered to be a severe monophasic syndrome characterized by bilateral optic neuritis (ON) and myelitis occurring in rapid succession. Furthermore, the prognosis for patients with NMO is often poor; within five years of disease onset, more than half of patients will develop severe bilateral visual impairment and even visual loss in at least one eye and /or inability to ambulate without assistance within 5 years of disease onset [2-4]. Serum NMO-immunoglobulin G (IgG) has been investigated, and its presence is highly specific for NMO [5,6]. However, NMOIgG is not detectable in all patients. Therefore, the diagnosis of NMO is generally based on the combination of clinical, neuroimaging, laboratory, and pathological findings [7,8]. It