Abstract
Objective Aquaporin-4 (AQP4) serum autoantibodies are detected by a variety of methods. The highest sensitivity is achieved with cell-based assays, but the enzyme-linked immunosorbent assay (ELISA) is still commonly utilized by clinicians worldwide. Methods We performed a retrospective review to identify all patients at the University of Utah who had AQP4 ELISA testing at ARUP Laboratories from 2010 to 2017. We then reviewed their diagnostic evaluation and final diagnosis based on the ELISA titer result. Results A total of 750 tests for the AQP4 ELISA were analyzed, and 47 unique patients with positive titers were identified. Less than half of these patients (49%) met the clinical criteria for neuromyelitis optica spectrum disorder (NMOSD). In cases of low positive titers (3.0–7.9 U/mL, n = 19), the most common final diagnosis was multiple sclerosis (52.6%). In the moderate positive cohort (8.0–79.9 U/mL, n = 14), only a little more than half the cohort (64.3%) had NMOSD. In cases with high positives (80–160 U/mL, n = 14), 100% of patients met clinical criteria for NMOSD. Conclusions Our data illustrates diagnostic uncertainty associated with the AQP4 ELISA, an assay that is still commonly ordered by clinicians despite the availability of more sensitive and specific tests to detect AQP4 autoantibodies in patients suspected of having NMOSD. In particular, low positive titer AQP4 ELISA results are particularly nonspecific for the diagnosis of NMOSD. The importance of accessibility to both sensitive and specific AQP4 testing cannot be overemphasized in clinical practice.
Highlights
Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory condition of the central nervous system (CNS) that preferentially affects the optic nerves, the spinal cord, and the juxtaventricular regions of the diencephalon and brainstem [1]
Published reports of the general utility of tests for aquaporin-4 immunoglobulin G (AQP4) include descriptions of immunohistochemistry, immunofluorescence (IF) [7], and immunoprecipitation assays (IPA), as well as enzyme-linked immunosorbent assay (ELISA) [8, 9] and, most recently, cell-based assays (CBA) and flow cytometry-/fluorescence-activated cell sorting (FACS) [10,11,12]
CSF data was available in three patients without NMOSD in the moderate positive ELISA cohort
Summary
Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory condition of the central nervous system (CNS) that preferentially affects the optic nerves, the spinal cord, and the juxtaventricular regions of the diencephalon and brainstem [1]. Recent international consensus guidelines outline major and minor criteria for diagnosis of NMOSD, of which antibody detection remains a central tenet [6]. The methodology of antibody detection has evolved greatly since its initial discovery. Published reports of the general utility of tests for AQP4 include descriptions of immunohistochemistry, immunofluorescence (IF) [7], and immunoprecipitation assays (IPA), as well as ELISA [8, 9] and, most recently, cell-based assays (CBA) and flow cytometry-/fluorescence-activated cell sorting (FACS) [10,11,12].
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