Characterization and Alternative Diagnoses in Patients with False-positive Aquaporin-4 Autoantibody Detection by Enzyme-Linked Immunosorbent Assay (ELISA) (P6.420)

Objective: To determine rate and characteristics of patients testing positive for autoantibodies to aquaporin-4 (AQP4) but not meeting diagnostic criteria for neuromyelitis optica spectrum disorders (NMOSD). Background: NMOSD represent a family of inflammatory central nervous system syndromes, variable in both clinical presentation and paraclinical markers, including the presence or absence of autoantibodies, primarily to AQP4. This antibody has been demonstrated to have direct pathogenicity. Seropositivity to AQP4 is predictive of both a higher clinical relapse rate and a favorable response to therapeutics. AQP4 autoantibodies are detected by a variety of methods; the highest sensitivity is achieved with cell-based assays and flow cytometry. Over 80% of patients with this disorder have detectable antibodies to AQP4. However, a minority of patients with positive testing do not meet clinical criteria for NMOSD. Design/Methods: We queried the medical record at the University of Utah for patients with a diagnosis of NMOSD. We then determined the proportion of positive AQP4 results by ELISA by test code at the regional reference laboratory, ARUP. The data were cross-referenced and we included all positive results from Aug 2010 through September 2017. A retrospective chart review was conducted to confirm or rule out a diagnosis of NMOSD. Results: Of all AQP4 ELISA ordered for the defined date range, 10% were positive (75/750). Of these, we identified and characterized cases not meeting diagnostic criteria for NMOSD and describe alternative diagnoses. Conclusions: We describe detection of AQP4 antibodies by ELISA in patients not meeting diagnostic criteria for NMOSD. More sensitive assays are available, the best of which is limited to 71% sensitivity. Systemic autoimmunity has been reported in seropositive individuals, compelling consideration of either alternative solitary processes or overlap with early or atypical NMOSD. Iterative testing via different methodologies should be considered in such cases, given the significant implications of incorrect diagnoses and immunosuppressive treatment. Disclosure: Dr. Williams has nothing to disclose. Dr. Peterson has nothing to disclose. Dr. Badger has nothing to disclose. Dr. Paz Soldan has received research support from Biogen. Dr. Greenlee has received personal compensation in an editorial capacity for Associate Editor for Medlink. Dr. Rose has received research support from Biogen. Dr Clardy has nothing to disclose.