title: Aquaporin-4 autoantibodies in neuromyelitis optica spectrum disorders: comparison between tissue-based and cell-based indirect immunofluorescence assays.
abstract: BACKGROUND
  Neuromyelitis optica spectrum disorders (NMOSD) are severe central nervous system inflammatory demyelinating disorders (CNS IDD) characterized by monophasic or relapsing, longitudinally extensive transverse myelitis (LETM) and/or optic neuritis (ON). A significant proportion of NMOSD patients are seropositive for aquaporin-4 (AQP4) autoantibodies. We compared the AQP4 autoantibody detection rates of tissue-based indirect immunofluorescence assay (IIFA) and cell-based IIFA.
  
  
  METHODS
  Serum of Chinese CNS IDD patients were assayed for AQP4 autoantibodies by tissue-based IIFA using monkey cerebellum and cell-based IIFA using transfected HEK293 cells which express human AQP4 on their cell membranes.
  
  
  RESULTS
  In total, 128 CNS IDD patients were studied. We found that 78% of NMO patients were seropositive for AQP4 autoantibodies by cell-based IIFA versus 61% by tissue-based IFA (p = 0.250), 75% of patients having relapsing myelitis (RM) with LETM were seropositive by cell-based IIFA versus 50% by tissue-based IIFA (p = 0.250), and 33% of relapsing ON patients were seropositive by cell-based IIFA versus 22% by tissue-based IIFA (p = 1.000); however the differences were not statistically significant. All patients seropositive by tissue-based IIFA were also seropositive for AQP4 autoantibodies by cell-based IIFA. Among 29 NMOSD patients seropositive for AQP4 autoantibodies by cell-based IIFA, 20 (69%) were seropositive by tissue-based IIFA. The 9 patients seropositive by cell-based IIFA while seronegative by tissue-based IIFA had NMO (3), RM with LETM (3), a single attack of LETM (1), relapsing ON (1) and a single ON attack (1). Among 23 NMO or RM patients seropositive for AQP4 autoantibodies by cell-based IIFA, comparison between those seropositive (n = 17) and seronegative (n = 6) by tissue-based IIFA revealed no differences in clinical and neuroradiological characteristics between the two groups.
  
  
  CONCLUSIONS
  Cell-based IIFA is slightly more sensitive than tissue-based IIFA in detection of AQP4 autoantibodies, which are highly specific for NMOSD.
authors.affiliation: University Department of Medicine, Queen Mary Hospital, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong. koonho@hkucc.hku.hk
authors.forename: Koon H
authors.initials: KH
authors.lastname: Chan
authors.forename: Jason S C
authors.initials: JS
authors.lastname: Kwan
authors.forename: Philip W L
authors.initials: PW
authors.lastname: Ho
authors.forename: Jessica W M
authors.initials: JW
authors.lastname: Ho
authors.forename: Andrew C Y
authors.initials: AC
authors.lastname: Chu
authors.forename: David B
authors.initials: DB
authors.lastname: Ramsden
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D051401:Aquaporin 4 / Q000276:immunology*; D001323:Autoantibodies / Q000032:analysis* / Q000276:immunology; D015153:Blotting, Western; D016009:Chi-Square Distribution; D020278:Demyelinating Autoimmune Diseases, CNS / Q000276:immunology*; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect / Q000379:methods*; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D008875:Middle Aged; D012680:Sensitivity and Specificity; D014162:Transfection
chemical_list: D051401:Aquaporin 4; D001323:Autoantibodies
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