Prediction of neuromyelitis optica attack severity by quantitation of complement-mediated injury to aquaporin-4-expressing cells.
BACKGROUND
Recent reports support a pathogenic role in neuromyelitis optica (NMO) for the aquaporin-4 (AQP4)-specific autoantibody (NMO-IgG). Neuromyelitis optica is an inflammatory demyelinating central nervous system disease, usually relapsing, that causes variable degrees of attack-related disability. The NMO-IgG binds in vitro to the extracellular domain of AQP4, activates complement, and causes astrocyte lesioning.


OBJECTIVE
To compare the prognostic utility of NMO-IgG titer and quantitative measures of complement-mediated injury to AQP4-expressing cells in NMO attacks.


METHODS
A retrospective clinical-serological correlative study at Mayo Clinic's Neuroimmunology Laboratory was undertaken. Over an 18-month period, we identified NMO-IgG-seropositive patients in whom sufficient serum and adequate clinical information pertaining to NMO attacks (6 severe, 6 mild) were available to analyze clinical-serological correlations. Sera from 9 patients with multiple sclerosis and 9 healthy subjects (all NMO-IgG seronegative) served as controls. Complement activation was measured by quantifying the number of green fluorescent protein-AQP4-transfected HEK 293 cells permeable to the viability dye propidium iodide after exposure to patient serum and active complement.


METHODS
Attack severity (mild or severe), percentage of AQP4-transfected cells lesioned, and NMO-IgG titer.


RESULTS
The median percentage of AQP4-transfected cells lesioned by complement in the presence of serum from patients with NMO was 14% for patients with mild attacks and 54% for patients with severe attacks (P = .005). Median complement activation values for sera from healthy subjects and patients with multiple sclerosis were 8% and 12%, respectively. Patients with mild NMO attacks and patients with severe NMO attacks did not differ significantly with respect to NMO-IgG titer (P = .089).


CONCLUSIONS
A laboratory measure of complement-mediated cell injury may serve as a prognostic biomarker in NMO. Larger prospective studies are required to validate this observation.
Hinson
Shannon R
SR
Department of Laboratory Medicine and Pathology, Hilton 3-78D, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
McKeon
Andrew
A
Fryer
James P
JP
Apiwattanakul
Metha
M
Lennon
Vanda A
VA
Pittock
Sean J
SJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D051401:Aquaporin 4 / Q000235:genetics / Q000276:immunology*; D001253:Astrocytes / Q000276:immunology; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D002460:Cell Line; D002648:Child; D003167:Complement Activation / Q000276:immunology*; D003165:Complement System Proteins / Q000276:immunology*; D005260:Female; D049452:Green Fluorescent Proteins; D006801:Humans; D007118:Immunoassay / Q000379:methods*; D007074:Immunoglobulin G / Q000032:analysis* / Q000097:blood; D008297:Male; D008875:Middle Aged; D009471:Neuromyelitis Optica / Q000097:blood / Q000175:diagnosis / Q000276:immunology*; D011237:Predictive Value of Tests; D011419:Propidium; D012189:Retrospective Studies; D055815:Young Adult
C496030:AQP4 protein, human; D051401:Aquaporin 4; D015415:Biomarkers; D007074:Immunoglobulin G; D049452:Green Fluorescent Proteins; D011419:Propidium; D003165:Complement System Proteins