AQP4 Antibody Assay Sensitivity Comparison in the Era of the 2015 Diagnostic Criteria for NMOSD

Abstract

We have compared five different assays for antibodies to aquaporin-4 in 181 cases of suspected Neuromyelitis optica spectrum disorders (NMOSD) and 253 controls to assess their relative utility. As part of a clinically-based survey of NMOSD in Australia and New Zealand, cases of suspected NMOSD were referred from 23 centers. Clinical details and magnetic imaging were reviewed and used to apply the 2015 IPND diagnostic criteria. In addition, 101 age- and sex-matched patients with multiple sclerosis were referred. Other inflammatory disease (n = 49) and healthy controls (n = 103) were also recruited. Samples from all participants were tested using tissue-based indirect immunofluorescence assays and a subset were tested using four additional ELISA and cell-based assays. Antibodies to myelin oligodendrocyte glycoprotein (MOG) were also assayed. All aquaporin-4 antibody assays proved to be highly specific. Sensitivities ranged from 60 to 94%, with cell-based assays having the highest sensitivity. Antibodies to MOG were detected in 8/79 (10%) of the residual suspected cases of NMOSD. Under the 2015 IPND diagnostic criteria for NMOSD, cell-based assays for aquaporin-4 are sensitive and highly specific, performing better than tissue-based and ELISA assays. A fixed cell-based assay showed near-identical results to a live-cell based assay. Antibodies to MOG account for only a small number of suspected cases.

Relapse Patterns in NMOSD: Evidence for Earlier Occurrence of Optic Neuritis and Possible Seasonal Variation

“…Cases of NMOSD were defined according to the 2015 IPND criteria (1). Testing for AQP4 antibodies was undertaken using either a tissue-based immunofluorescence technique or positivity on a least two cellbased assays (fixed, Euroimmun R or live, Oxford) as previously described (5). Testing for MOG antibodies was conducted using a live cell-based assay as previously described (5).…”

“…Testing for AQP4 antibodies was undertaken using either a tissue-based immunofluorescence technique or positivity on a least two cellbased assays (fixed, Euroimmun R or live, Oxford) as previously described (5). Testing for MOG antibodies was conducted using a live cell-based assay as previously described (5). Age-and sex-matched MS cases were identified from each centre with the diagnosis of MS being confirmed according to the 2010 McDonald criteria (7) with the added requirements of having no clinical features suspicious for NMOSD and being negative for AQP4 antibodies.…”

“…There were 101 controls with MS who were all negative for AQP4 antibodies and met the 2010 McDonald criteria (7). Testing for MOG antibodies was conducted on 42/75 (56%) of NMOSD cases, including all of the seronegative cases and 52/101 (51%) of MS controls, and all were negative (5). The demographic and clinical features of the NMOSD cases and MS controls have been previously reported (6) and show that they were well matched for age and sex, but differ in a number of predictable clinical features as summarized in Table 1.…”

“…We have previously reported on the incidence and prevalence (4), AQP4 antibody assay findings (5) and clinical features (6) of a sizeable cohort of NMOSD cases meeting the 2015 International Panel for NMO Diagnosis (IPND) diagnostic criteria (1) collected from Australia and New Zealand. Here we analyze the specific details of relapse patterns, use of acute therapies and temporal patterns both in relation to the calendar year and across the lifespan of the disease.…”

Metabolomic Profiling in Neuromyelitis Optica Spectrum Disorder Biomarker Discovery

“…Immunoglobulin G 1 (IgG 1 ) autoantibodies (Ab) that target the astrocyte aquaporin-4 (AQP4) water channel have been detected in approximately 70% of NMOSD patients worldwide [ 6 , 7 , 8 , 9 ]. However, this estimate may be underestimated, because not all testing used the more sensitive diagnostic AQP4 cell-based assay (CBA) [ 10 , 11 ]. AQP4-Ab binds to and internalizes AQP4 expressed on astrocyte end feet surrounding blood vessels and synapses [ 4 , 6 , 12 , 13 , 14 , 15 ].…”