Identification of Novel Serum Proteins Associated with Myelination and Cholesterol Transport in Neuromyelitis Optica Spectrum Disorders by Mass Spectrometry

Abstract

Neuromyelitis optica spectrum disorders (NMOSD) is a demyelinating autoimmune disease affecting the central nervous system causing inflammatory lesions in the optic nerves, spinal cord and other vital areas of CNS. The clinical manifestations include acute transverse myelitis with paraplegia and optic neuritis with impaired vision. In the present study we focussed on comparative expression of serum proteins between NMOSD variants and control. The study has identified a plethora of novel and unexplored acute phase proteins involved in lipid transport and myelination in perspective of NMOSD. The serum proteins obtained after albumin globulin depletion were subjected to LC-MS/MS. The commonly altered proteins in all NMOSD variants with respect to control were smaug homolog protein and serum amyloid A. Truncated breast and ovarian cancer susceptibility protein and cystic fibrosis transmembrane conductance regulator protein were specifically upregulated and can act as potential biomarkers for neuromyelitis optica with autoantibody negativity to Aquaporin - 4 (AQP-4) and myelin oligodendrocyte (MOG) immunoglobulins. In addition, the uniquely downregulated proteins such as antithrombin III and histidine rich glycoprotein in NMO/MOG autoantibody negative samples can be accounted for its dysregulated fibrinolysis associated with NMO. The differentially expressed proteins were involved in cholesterol transport, synaptic vesicle mediated transport, neurotransmission and immune regulation which are closely associated with myelin formation and protection.

Supplementary information: The online version contains supplementary material available at 10.1007/s12291-021-01004-w.

Keywords: Acute phase reactant; Complement; Demyelination; Optic neuritis; Smaug homolog protein.

Fig. 1

Venn diagram showing the differentially expressed proteins between control and NMOSD variants. A – Control, B/A—The DEPs in MOG Ab ^+ve sample with respect to control, C/A –The DEPs in MOG & AQP4 autoantibody negative with respect to control, D /A –The DEPS in AQP4 Ab^+ve sample with respect to control

Fig. 2

Pie-chart of the biological processes of the differentially expressed proteins in the three NMOSD variants. Lipid metabolic process and lipid transport, apoptotic process and response to stress, immune system process, synaptic vesicle exocytosis and vesicle mediated transport are the major BPs of the DEPs in the three NMOSD variants