Identification of potential biomarkers for neuromyelitis optica by quantitative proteomics.

ABSTRACT

OBJECTIVE: Neuromyelitis optica (NMO) was a serious autoimmune inflammatory condition affecting the central nervous system. Currently, there was a lack of diagnostic biomarkers for AQP4-IgG-negative NMO patients. METHODS: A comparative proteomic analysis was conducted on the CSF of 10 patients with NMO and 10 patients with non-inflammatory neurological disorders (NND) using tandem mass tagging technology. Differentially expressed proteins (DEPs) were analyzed using bioinformatic methods. The candidate proteins were then validated through ELISAs in a subsequent cohort of 160 samples, consisting of paired CSF and plasma samples from 50 NMO patients, CSF samples from 30 NND patients, and plasma samples from 30 healthy individuals. RESULTS: We identified 389 proteins via proteomics, screening 79 DEPs. NCAM1, SST and AHSG were selected as candidate molecules for further validation. Compared to NND patients, there were decreased levels of AHSG in CSF and increased levels of NCAM1 and SST in NMO patients. The ELISA results revealed significantly higher levels of AHSG, SST and NCAM1 in the CSF of the NMO group compared to the NND group. Similarly, the serum levels of these three proteins were also higher in the NMO group compared to the healthy control group. It was found that serum NCAM1 levels significantly decreased in patients with non-relapsed NMO compared to patients with relapsed NMO and CSF NCAM1 level increased in patients with bilateral NMO compared to patients with unilateral NMO. Furthermore, CSF SST levels increased in AQP4 antibody-positive NMO patients compared to AQP4 antibody-negative patients. INTERPRETATION: CSF NCAM1, serum NCAM1 and serum SST may serve as potential biomarkers for NMO patients and aid in the diagnosis of AQP4 antibody-negative NMO patients.