Plasma complement biomarkers distinguish multiple sclerosis and neuromyelitis optica spectrum disorder

摘要

Background: Multiple sclerosis (MS) and neuromyelitis optica spectrum disordersud(NMOSD) are autoimmune demyelinating diseases distinguished clinically by selectiveudinvolvement in NMOSD of optic nerves and spinal cord. Early clinical manifestations areudsimilar, complicating clinical management. Aquaporin-4 autoantibody measurement aidsuddiagnosis of NMOSD but is frequently negative, creating unmet need for alternativeudbiomarkers.udObjective: We investigated whether plasma complement proteins are altered in MS andudNMOSD and whether these provide biomarkers that reliably distinguish the diseases.udMethods: Plasma from 53 NMOSD, 49 MS and 69 control donors was tested in multiplexudassays measuring complement activation products and proteins. Logistic regression was usedudto test whether combinations of complement analyte measurements distinguish NMOSD fromudcontrols and MS.udResults: All activation products were significantly elevated in NMOSD compared to eitherudcontrol or MS. Four complement proteins (C1inh, C1s, C5, FH) were significantly higher inudNMOSD compared to MS or controls. A model comprising C1 inhibitor and TCCuddistinguished NMOSD from MS (area under curve (AUC) 0.98), while C1 inhibitor and C5uddistinguished NMOSD from controls (AUC 0.94).udConclusions: NMOSD is distinguished from MS by plasma complement activation.