AQP4-IgG Testing for NMOSD Is Highly Specific and Highly Sensitive

A team of researchers, in determining the utility of aquaporin 4 IgG (AQP4-IgG) testing for neuromyelitis optica spectrum disorder (NMOSD), discovered it was highly specific and sensitive for diagnosing NMOSD in a high throughput setting. 

NMOSD, an inflammatory central nervous system demyelinating disease, is associated with AQP4-IgG. The authors of this paper previously demonstrated that AQP4-IgG live cell-based assay had a 100% specificity and 83% sensitivity for diagnosing neuromyelitis optica (NMO) under the 2006 criteria. Some forms of NMOSD were previously classified as NMO. New criteria were defined in 2015.

For this study, “our aim was to assess the sensitivity, specificity, likelihood ratios and frequency of false positives with AQP4-IgG live cell-based assay using updated 2015 NMOSD diagnostic criteria in a high throughput clinical setting at a tertiary referral center,” Redenbaugh et al said. 

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They thus performed a retrospective observational study of 1371 patients seen at the Mayo Clinic between January 2018 and December 2019. The participants in this study had their serum AQP4-IgG evaluated during routine clinical care. “Electronic medical records and MRIs were available in all patients and reviewed to determine age at testing, sex, ethnicity, clinical and radiologic phenotypes to determine if they fulfilled the 2015 criteria for NMOSD,” the research team wrote. 

The results demonstrated that out of the 1371 participants, 41 tested positive for AQP4-IgG. All these patients fulfilled contemporary criteria for NMOSD with AQP4-IgG. Impressively, there were no false positives, the AQP4-IgG specificity was 100%, and positive likelihood ratios were not calculable as specificity was 100%. 

“Our data show that AQP4-IgG seropositivity has high sensitivity and extremely high specificity for NMOSD diagnosis in a real-world clinical setting, consistent with our prior study using 2006 NMO criteria,” the authors of the study wrote. “The lack of false positive results, despite testing large numbers attests to the value of live cell-based AQP4-IgG assays as a diagnostic biomarker for NMOSD.” 

Reference

Redenbaugh V, Montalvo M, Sechi E, et al. Diagnostic value of aquaporin-4-IgG live cell based assay in neuromyelitis optica spectrum disorders. Mult Scler J Exp Transl Clin. Published online November 26, 2021. doi:10.1177/20552173211052656