Serum Molecular Biomarkers in Neuromyelitis Optical and Multiple Sclerosis

Abstract ObjectiveThe aims of this study were to determine whether the expression levels of serological cytokines could distinguish 1) neuromyelitis optical spectrum disorders (NMOSD) from healthy controls (HCs); and 2) NMOSD patients with and without the aquaporin-4 (AQP-4) antibody biomarker from each other; and 3) NMOSD patients without antibody to AQP-4 from multiple sclerosis (MS). MethodsThe expression levels of 200 proteins in serum from 41 NMOSD (32 with antibodies to AQP-4, 9 without antibodies to AQP-4), 12 MS patients, and 34 HCs were measured using glass-based antibody arrays. In parallel, the correlation between protein expression in NMOSD/MS patients and clinical traits was analyzed with Weighted Gene Co-expression Network Analysis (WGCNA).ResultsThirty-nine serological proteins were differentially expressed in NMOSD patients compared to HCs. 29 differentially-expression proteins (DEPs) were specific to NMOSD whereas 10 of these were observed in NMOSD and MS samples. In addition, there were 15 DEPs between AQP-4-IgG seronegative and AQP-4-IgG seropositive NMOSD patients, and 9 DEPs between NMOSD and MS patients who did not have AQP-4-IgG. ConclusionsOur findings highlight that serological Interleukin-17B (IL-17B) may be key biomarker of NMOSD and MS. While epidermal growth factor (EGF) may be correlated with the breakdown of the blood-brain barrier in NMOSD patients, granulocyte chemotactic protein-2 (GCP-2) and monocyte differentiation antigen CD14 (CD14) may play different roles in the pathogenesis of AQP-4-IgG seronegative and seropositive NMOSD and MS. Novel biomarkers identified in our study could potentially be used in the diagnosis and treatment of NMOSD.Trial registrationPublic title: Multi-Center Clinical Study of GFAP AstrocytopathyRegistration number: ChiCTR2000041291Date of registration: 2020-12-23 (Retrospective registration)URL of trail registry record: http://www.chictr.org.cn/showproj.aspx?proj=65306