Aquaporin-4 autoantibodies in neuromyelitis optica spectrum disorders: comparison between tissue-based and cell-based indirect immunofluorescence assays.
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.
Chan
Koon H
KH
University Department of Medicine, Queen Mary Hospital, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong. koonho@hkucc.hku.hk
Kwan
Jason S C
JS
Ho
Philip W L
PW
Ho
Jessica W M
JW
Chu
Andrew C Y
AC
Ramsden
David B
DB
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
D051401:Aquaporin 4; D001323:Autoantibodies
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