Background: Multiple sclerosis (MS) and neuromyelitis optica spectrum disorders
(NMOSD) are autoimmune demyelinating diseases distinguished clinically by selective
involvement in NMOSD of optic nerves and spinal cord. Early clinical manifestations are
similar, complicating clinical management. Aquaporin-4 autoantibody measurement aids
diagnosis of NMOSD but is frequently negative, creating unmet need for alternative
biomarkers.
Objective: We investigated whether plasma complement proteins are altered in MS and
NMOSD and whether these provide biomarkers that reliably distinguish the diseases.
Methods: Plasma from 53 NMOSD, 49 MS and 69 control donors was tested in multiplex
assays measuring complement activation products and proteins. Logistic regression was used
to test whether combinations of complement analyte measurements distinguish NMOSD from
controls and MS.
Results: All activation products were significantly elevated in NMOSD compared to either
control or MS. Four complement proteins (C1inh, C1s, C5, FH) were significantly higher in
NMOSD compared to MS or controls. A model comprising C1 inhibitor and TCC
distinguished NMOSD from MS (area under curve (AUC) 0.98), while C1 inhibitor and C5
distinguished NMOSD from controls (AUC 0.94).
Conclusions: NMOSD is distinguished from MS by plasma complement activation
