Plasma complement biomarkers distinguish multiple sclerosis and neuromyelitis optica spectrum disorder.
BACKGROUND
Multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) are autoimmune inflammatory demyelinating diseases of the central nervous system. Although distinguished by clinicoradiological and demographic features, early manifestations can be similar complicating management. Antibodies against aquaporin-4 support the diagnosis of NMOSD but are negative in some patients. Therefore, there is unmet need for biomarkers that enable early diagnosis and disease-specific intervention.


OBJECTIVE
We investigated whether plasma complement proteins are altered in MS and NMOSD and provide biomarkers that distinguish these diseases.


METHODS
Plasma from 54 NMOSD, 40 MS and 69 control donors was tested in multiplex assays measuring complement activation products and proteins. Using logistic regression, we tested whether combinations of complement analytes distinguished NMOSD from controls and MS.


RESULTS
All activation products were elevated in NMOSD compared to either control or MS. Four complement proteins (C1inh, C1s, C5 and FH) were higher in NMOSD compared to MS or controls. A model comprising C1inh and terminal complement complex (TCC) distinguished NMOSD from MS (area under the curve (AUC): 0.98), while C1inh and C5 distinguished NMOSD from controls (AUC: 0.94).


CONCLUSIONS
NMOSD is distinguished from MS by plasma complement biomarkers. Selected complement analytes enable differential diagnosis. Findings support trials of anti-complement therapies in NMOSD.
Institute of Infection & Immunity, School of Medicine, Cardiff University, Cardiff, UK.
Svetlana
S
Hakobyan
Institute of Neurosciences and Mental Health, Cardiff University, Cardiff, UK.
Sebastian
S
Luppe
School of Medicine, Cardiff University, Cardiff, UK.
David Rs
DR
Evans
Institute of Neurosciences and Mental Health, Cardiff University, Cardiff, UK.
Katharine
K
Harding
Institute of Neurosciences and Mental Health, Cardiff University, Cardiff, UK.
Samantha
S
Loveless
Institute of Neurosciences and Mental Health, Cardiff University, Cardiff, UK.
Neil P
NP
Robertson
Institute of Infection & Immunity, School of Medicine, Cardiff University, Cardiff, UK.
B Paul
BP
Morgan
D000328:Adult; D000368:Aged; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D050718:Complement C1 Inhibitor Protein / Q000032:analysis; D003182:Complement C5 / Q000032:analysis; D015938:Complement Membrane Attack Complex / Q000032:analysis; D003165:Complement System Proteins / Q000032:analysis*; D003937:Diagnosis, Differential; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D016014:Linear Models; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology; D009471:Neuromyelitis Optica / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology; D011237:Predictive Value of Tests; D011379:Prognosis; D012372:ROC Curve; D055815:Young Adult
D015415:Biomarkers; D050718:Complement C1 Inhibitor Protein; D003182:Complement C5; D015938:Complement Membrane Attack Complex; C469952:SERPING1 protein, human; D003165:Complement System Proteins
Multiple sclerosis; biomarker; complement; inflammation; neuromyelitis optica