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Updated: Jan 17, 2026
Human Serum Anti-aquaporin-4 Immunoglobulin G Detection by Cell-based Assay
Published on: April 5, 2019
Frequency of Seroconversion in Aquaporin-4 Antibody Testing: Insights From Real-World Data
Tatchaporn Ongphichetmetha1,2, Mengke Du1, Nisa Vorasoot3,4
1Neurology, Cleveland Clinic Neurological Institute, Mellen Center for Multiple Sclerosis, Cleveland, Ohio, USA.
Insights
Repeat testing for aquaporin-4-immunoglobulin G (AQP4-IgG) is rarely beneficial after a negative cell-based assay (CBA). Seroconversion is uncommon after negative immunofluorescence assays (IFA), suggesting limited yield from serial AQP4-IgG testing.
Area of Science:
- Neurology
- Immunology
- Clinical Diagnostics
Background:
- Aquaporin-4-immunoglobulin G (AQP4-IgG) antibodies are key biomarkers for neuromyelitis optica spectrum disorder (NMOSD).
- Clinicians frequently retest AQP4-IgG to detect seroconversion, especially when initial results are negative.
- Cell-based assays (CBA) offer superior sensitivity compared to older immunofluorescence assays (IFA).
Purpose of the Study:
- To evaluate the frequency of AQP4-IgG seroconversion in patients with an initial negative test result.
- To compare seroconversion rates between patients tested with CBA versus IFA.
Main Methods:
- Retrospective cohort study of 451 patients tested between 2006 and 2024 at Cleveland Clinic.
- Analysis of serial AQP4-IgG testing results based on the initial assay method (CBA or IFA).
Main Results:
- No seroconversion was observed in 263 patients initially tested by CBA.
- Seroconversion occurred in 4.3% (7/170) of patients initially tested by IFA.
- Repeat AQP4-IgG testing showed a low yield for seroconversion, particularly after negative CBA results.
Conclusions:
- Negative CBA results for AQP4-IgG are highly reliable, with minimal risk of subsequent seroconversion.
- Repeat AQP4-IgG testing is generally not recommended after a negative CBA.
- Serial testing may have limited utility after a negative IFA, but is less indicated than previously thought.
Abstract:
Clinicians often repeat aquaporin-4-immunoglobulin G (AQP4-IgG) testing in case of possible seroconversion. Compared with older, less sensitive immunofluorescence assays (IFA), cell-based assays (CBA) offer higher sensitivity. This study assessed the frequency of seroconversion in a retrospective Cleveland Clinic cohort (2006-2024) of 451 patients with an initial negative AQP4-IgG result who underwent serial testing. Seroconversion occurred in 4.3% (7/170) of patients initially tested by tissue IFA, but in none (0/263) of those tested by CBA. The lack of AQP4-IgG seroconversion after a negative CBA, with only rare cases after a negative IFA, suggests that repeat AQP4-IgG testing is low yield unless prior testing used older methods such as IFA.
