Frequency of Seroconversion in Aquaporin-4 Antibody Testing: Insights from Real-World Data
Tatchaporn Ongphichetmetha1, Mengke Du2, Nisa Vorasoot3, Sean Pittock4, Jeffrey Cohen2, Amy Kunchok1
1Cleveland Clinic - Mellen Centre, 2Cleveland Clinic, 3Department of Neurology, Laboratory Medicine and Pathology, and Center for Multiple Sclerosis and Autoimmune Neurology, Mayo Clinic College of Medicine, Rochester, Minnesota, United States, 4Mayo Clinic Dept of Neurology
Objective:
To assess the frequency of AQP4-IgG seroconversion across different testing methods in a large real-world clinical database.
Background:
Seroconversion of aquaporin-4 immunoglobulin G (AQP4-IgG) from negative to positive has been reported in a few cases. There is concern that seronegative neuromyelitis optica spectrum disorder (NMOSD) cases should be serially tested. Data from real-world clinical practice are needed to guide AQP4-IgG testing.
Design/Methods:
This retrospective clinical cohort included all patients with ≥2 AQP4-IgG tests, with the first test negative, between 2006-2024 by all methods (CBA (fixed and live), IFA, or ELISA). The frequency of seroconversion was evaluated.
Results:
451 individuals with ≥2 AQP4-IgG tests with their first test negative were included. The mean age was 41 years (SD 15) and 330 (73%) were female. The median number of tests was 2 (range: 2–6), with a median follow-up period of 6.4 years (IQR: 3–10). Of the 451 individuals, the first negative test was CBA in 263 (58%), IFA in 170 (38%), ELISA in 4 (1%), and IFA plus ELISA in 14 (3%). Seroconversion of AQP4-IgG was identified in 8/451 individuals (1.8%) with NMOSD all first tested by IFA (8/170, 4.7%). Among the 8 seroconverters, 5 were subsequently positive by IFA, 2 by IFA plus ELISA and 1 by CBA. No seroconversions were observed among 263 with an initial negative CBA test.
Conclusions:
There were no cases of seroconversion in patients first tested by CBA methods suggesting repeat AQP4-IgG testing in patients initially negative by CBA has limited clinical value. All seroconversion cases occurred in patients first tested with IFA, likely reflective of the known low sensitivity of this method. Therefore, repeat testing may be useful in patients with a clinical diagnosis of NMOSD and early negative IFA test.
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