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Aquaporin 4 -antibodies (AQP-4)
Aquaporin 4 (AQP4) is a water channel protein found on cells known as astrocytes that surround the blood-brain barrier, (a layer of cells responsible for preventing dangerous substances in the blood from crossing into the brain). It is presumed that the blood brain barrier allows the AQP4 antibodies to enter the central nervous system. This causes an inflammation and demyelination and symptoms of a relapse.
Approximately 80% of people diagnosed with NMOSD have Aquaporin 4 antibodies in their blood.
Aquaporin 4 test at John Radcliffe Hospital, Oxford
Since the discovery of Aquaporin 4 antibodies in the serum of patients with Neuromyelitis Optica many research laboratories around the world have developed assays to detect these antibodies. Oxford have developed their own cell-based assay, with 76% sensitivity and 100% specificity.
As part of the NMOSD UK service, Aquaporin 4 antibody testing is free at John Radcliffe Hospital.
When to test for AQP4 Antibodies
- If a patient has recurrent, bilateral or severe optic neuritis
- If a patient has longitudinal, or recurrent transverse myelitis
- If lumbar MRI spine shows a lesion greater than 3 vertebrae
- If a patient has poor recovery from MS relapses
If the test is positive, please refer the patient into one of the centres.
However 20% of people with NMOSD do not have Aquaporin 4 antibodies,
If you have any concerns regarding diagnosis or management, please refer to the NMO service.
Serologic diagnosis of NMO
A multicenter comparison of aquaporin-4-IgG assays
P.J. Waters, PhD* A. McKeon, MB, MRCPI M.I. Leite, MD, DPhil S. Rajasekharan, PhD V.A. Lennon, MD, PhD A. Villalobos, MSc J. Palace, DM, FRCP J.N. Mandrekar, PhD A. Vincent, MBBS, FRCPath A. Bar-Or, MD, FRCP(C) S.J. Pittock, MD*
Objectives: Neuromyelitis optica (NMO) immunoglobulin G (IgG) (aquaporin-4 [AQP4] IgG) is highly
specific for NMO and related disorders, and autoantibody detection has become an essential
investigation in patients with demyelinating disease. However, although different techniques are
now used, no multicenter comparisons have been performed. This study compares the sensitivity
and specificity of different assays, including an in-house flow cytometric assay and 2 commercial
assays (ELISA and transfected cell-based assay [CBA]).
Methods: Six assay methods (in-house or commercial) were performed in 2 international centers
using coded serum from patients with NMO (35 patients), NMO spectrum disorders (25 patients),
relapsing-remitting multiple sclerosis (39 patients), miscellaneous autoimmune diseases (25 patients),
and healthy subjects (22 subjects).
Results: The highest sensitivities were yielded by assays detecting IgG binding to cells expressing
recombinant AQP4 with quantitative flow cytometry (77%; 46 of 60) or visual observation (CBA,
73%; 44 of 60). The fluorescence immunoprecipitation assay and tissue-based immunofluorescence
assay were least sensitive (48%–53%). The CBA and ELISA commercial assays (100%
specific) yielded sensitivities of 68% (41 of 60) and 60% (36 of 60), respectively, and sensitivity
of 72% (43 of 60) when used in combination.
Conclusions: The greater sensitivity and excellent specificity of second-generation recombinant
antigen-based assays for detection of NMO-IgG in a clinical setting should enable earlier diagnosis
ofNMOspectrum disorders and prompt initiation of disease-appropriate therapies.