Objective: We have undertaken a clinical survey of neuromyelitis optica spectrum disorder (NMOSD) across Australia and New Zealand. We aimed to measure the sensitivity and specificity of six assays for aquaporin 4 (AQP4) antibodies using the 2015 Wingerchuk diagnostic criteria.

Background: The detection of antibodies to AQP4 is of great value in confirming the diagnosis of NMOSD. We have assessed the value of various assays with the new diagnostic criteria.

Design/Methods: We performed a clinical survey of NMOSD through 23 demyelinating disease clinics. Identification of cases was based on clinical criteria using features identified as high risk for NMOSD. Demographic and clinical information were recorded using a standard questionnaire. NMOSD cases were defined using the 2015 Wingerchuk criteria. Controls were a mixture of typical multiple sclerosis (MS) and blood donors. AQP4 antibodies were assessed using 6 different assays: immunofluorescence on mouse brain and kidney; ELISA; Euroimmun AQP4 M1/M23 fixed cell preparation; Euroimmun AQP4/MOG fixed cell preparation and a live cell-based assay.

Results: One suspected case was positive for anti-MOG antibodies and was excluded. NMOSD was confirmed in 79 cases. The median age was 47 (range 15 – 85) years and 71/79 (91%) were female. Controls were 50 MS cases and 98 blood donors. For immunofluorescence sensitivity was 60/74 (81%) positives and specificity was 148/148 (100%) negatives. Receiver-operator curve analysis indicated that an ELISA cut-off titre of 10 gave optimal sensitivity and specificity. Results for all six assays were available for a subset of 30 cases and 96 controls. Sensitivity ranged from 63% for the ELISA test through to 97% for the live cell-based assay. Specificity was 99% or higher for all assays.

Conclusions: Cell-based assays were more sensitive than immunofluorescence or ELISA. All assays were highly specific for NMOSD. Cell-based assays for AQP4 remain the most sensitive method for confirming a diagnosis of NMOSD.

Study Supported by: This work was supported by Multiple Sclerosis Research Australia, Brain Foundation, CASS, Gold Coast Hospital Foundation and Griffith University.

Disclosure: Dr. Prain has nothing to disclose. Dr. Waters has nothing to disclose. Dr. Clarke has nothing to disclose. Dr. Collaboration has nothing to disclose. Dr. Vincent has nothing to disclose. Dr. Broadley has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Bayer-Schering, Biogen, Merck Serono, Novartis, and Sanofi. Dr. Broadley has received research support from Biogen.