Decipher potential biomarkers of diagnosis and disease activity for NMOSD with AQP4 using LC-MS/MS and Simoa

Neuromyelitis optica spectrum disorders (NMOSD) is an autoimmune demyelinating disease, leading recurrently relapses and severe disability. There is a need for new biomarkers to meet clinical needs in diagnosis and monitoring.

Through liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) analysis, brain lesions from NMO animal models were analyzed to identify potential biomarkers. Then, we assessed the levels of serum glial fibrillary acidic protein (sGFAP), neurofilament light chain (sNfL), Tau protein (sTau) and Ubiquitin C-terminal hydrolase L1 (sUCHL1) using an ultrasensitive single molecule array (Simoa) of AQP4-IgG + NMOSD patients, myelin oligodendrocyte glycoprotein antibody-associated disorder (MOGAD) patients, multiple sclerosis (MS) patients and healthy controls (HCs). Additionally, we further explored the early diagnosis value of these proteins.

There were 72 differentially expressed proteins between the NMO and control groups. NfL abundance was elevated when GFAP, UCHL1, and Tau abundance was decreased in the NMO group. Then, we observed that the sGFAP and sUCHL1 levels in patients with NMOSD in the early stage were significantly increased compared to those in control participants. Combined ROCs of the sGFAP, sNfL, and sUCHL1 levels to better predict NMOSD with relapse stages was optimal. Notably, univariate and multivariate analyses demonstrated that the sGFAP and sNfL levels were higher in patients with brain lesions, while the sUCHL1 levels were higher in those with spinal cord lesions during recent relapse.

These findings suggested that sGFAP, sNfL, and sUCHL1 displayed good diagnostic performance in AQP4-IgG + NMOSD and could be novel candidates for early discrimination.