NMOSD and MOGAD: Laboratory Support of Diagnosis and Management
NMOSD and MOGAD: Laboratory Support of Diagnosis and Management
This Clinical Focus provides an overview of the use of laboratory testing to diagnose and manage neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein antibody disease (MOGAD).
Clinical Focus
NMOSD and MOGAD
Laboratory Support of Diagnosis and Management
Clinical background [return to contents]
Neuromyelitis optica (NMO, also known as Devic’s disease) is an immune-mediated inflammatory disease that predominantly affects the optic nerve and spinal cord. The term NMO spectrum disorders (NMOSD) encompasses limited and early forms of NMO and related conditions. In 2015, NMO and NMOSD were unified under the term NMOSD.1 Myelin oligodendrocyte glycoprotein antibody disease (MOGAD) is a disease with overlapping, but distinct, features compared with NMOSD.2 Accurate diagnosis of these conditions is important because approved targeted treatments for NMOSD have become available and treatments used for conditions with similar symptoms, such as multiple sclerosis (MS), can harm patients with NMOSD.1,3,4
This Clinical Focus discusses how laboratory testing supports diagnosis and management of NMOSD and MOGAD. The material is provided for informational purposes only and is not intended as medical advice. Test selection and interpretation, diagnosis, and patient management decisions should be based on the physician’s education, clinical expertise, and assessment of the patient.
NMOSD
Most patients with NMOSD test positive for antibodies to aquaporin-4 (AQP4, Table 1), a water channel protein responsible for homeostatic balance and clearing waste from the brain among other functions within the central nervous system. The disease more frequently affects women and the age of onset is usually between 30 and 40 years.5
Table 1. Diagnostic Criteria for Neuromyelitis Optica Spectrum Disorders (NMOSD) [return to contents]
Presence of AQP4-IgG1 |
Absence of AQP4-IgG or unknown status1 |
|
|
Core clinical characteristics
|
|
Possible alternative diagnosesb
|
|
| AQP4, aquaporin-4; MRI, magnetic resonance imaging; MOGAD, myelin oligodendrocyte glycoprotein antibody disorder. | |
| a | At least 1 characteristic must be optic neuritis, acute myelitis with longitudinally extensive transverse myelitis (LETM), or area postrema syndrome; dissemination in space; fulfill additional MRI requirements (see reference 1 for details). |
| b | See references 1 and 2 for specific red flags that indicate alternative diagnoses. |
Diagnostic criteria for NMOSD are organized based on the presence or absence of AQP4 IgG antibody. For AQP4 IgG-positive patients, diagnosis requires the presence of at least 1 core clinical characteristic and the exclusion of alternative diagnoses (Table 1). For AQP4 IgG-negative patients and those with unknown AQP4-IgG status, criteria are more stringent. In addition to exclusion of alternative diagnoses, at least 2 clinical characteristics must be present; furthermore, the type and location of the characteristics matter, and additional magnetic resonance imaging (MRI) requirements may need to be met (Table 1).1 Several disease-modifying drugs have been approved for NMOSD for AQP4 IgG-positive patients.3
MOGAD
Most patients with MOGAD test positive for MOG antibodies, which target MOG, a glycoprotein on the outermost myelin membranes surrounding the optic nerves, spinal cord, and brain. Patients with MOGAD tend to be younger6,7 and, as a group, are less predominantly female compared with NMOSD patients who test positive for AQP4 antibodies.2,7–9 The core MOGAD clinical phenotypes include optic neuritis (up to 80% of patients), transverse myelitis (30% to 50%), acute disseminated encephalomyelitis (ADEM, 5% in adults, up to 40% in children), cerebral monofocal or polyfocal deficits, brainstem or cerebellar deficits (up to 34% of patients), and cerebral cortical encephalitis often with seizures (approximately 7%).2,10–12
Overall, patients with MOGAD have milder disease and more favorable outcomes compared with patients with AQP4 antibody-positive NMOSD.7,13–16 For example, a small prospective study conducted over 18 months found less severe clinical attacks and better prognoses among patients with MOGAD (n=15) than among those with AQP4 antibody-positive NMOSD (n=15).17 Compared with AQP4 antibody-positive NMOSD patients, those with MOGAD or double-seronegative NMOSD (negative NMOSD and MOG antibodies) had lower rates of disability and lower expanded disability status.18 Relapse rates tend to be lower in MOGAD compared with NMOSD,6,8,9,19 and patients with MOGAD tend to be more responsive to steroid therapy compared with patients with NMOSD.2,15
Proposed diagnostic criteria for MOGAD consist of 3 requirements: a positive MOG-IgG test, presence of a core clinical phenotype, and the exclusion of an alternative diagnoses such as multiple sclerosis.20 Serum specimens are recommended for all patients undergoing MOG-IgG testing; however, cerebrospinal fluid (CSF) may be valuable in patients with suspected MOGAD but in whom serum testing is negative for MOG-IgG.20 Positive CSF MOG-IgG (and negative serum IgG) or positive serum MOG-IgG but low MOG-IgG titers (or without titers) should be supported with negative AQP4-IgG status and ≥1 clinical or MRI feature.20
Individuals suitable for testing [return to contents]
- Individuals with suspected NMOSD (Table 1) or MOGAD (overlapping clinical features with NMOSD but comparatively more prevalent in younger patients and children with ADEM)
Test availability and selection [return to contents]
Quest Diagnostics offers cell-based assays (CBAs) for testing AQP4 (test code 93893) or MOG antibodies (test code 36952, Table 2) in serum and to assist in differential diagnosis.
CBAs are strongly recommended for AQP4. Tests are also available in CSF. It is rare that a patient’s results for AQP4 in serum will differ from their results in CSF. Therefore, guidelines do not recommend routine CSF testing in AQP4-seronegative patients.1 AQP4 antibody tests are also offered with reflex to titer (test codes 38321 [serum] and 93893 [CSF]).
Enzyme-linked immunosorbent assay (ELISA) testing is also available for AQP4 (test code 90382). However, CBAs have higher sensitivity (77% vs 63%–64% for indirect immunofluorescence or ELISA) and lower false-positive rates (0.1% among MS patients vs 0.5%–1.3% for ELISA).1
A serum CBA is recommended for all patients undergoing MOG-IgG testing, but a CSF MOG-IgG CBA (test code 36954) is available for those with suspected MOGAD who have negative serum test results.20 The MOG antibody tests reflex to titer.
For differential diagnosis, Quest also offers the NMO Spectrum Evaluation in serum (test code 38312) or CSF (test code 38313), which begins with AQP4 testing and reflexes to MOG testing if AQP4 is negative (Table 2).
Table 2. Available Tests for NMOSD and MOGAD [return to contents]
Test code |
Assay |
Method |
Clinical use |
Serum |
|||
Aquaporin-4 (AQP4) (NMO-IgG) Antibody With Reflex to Titer, Seruma,b |
CBA |
Diagnose NMOSD and assess prognosis |
|
Myelin Oligodendrocyte Glycoprotein (MOG) Antibody With Reflex to Titer, Seruma,b |
CBA |
Diagnose MOGAD and assess need for follow-up testing if low titerc |
|
NMO Spectrum Evaluation (AQP4 With Reflex to MOG), Seruma,b Includes AQP4 antibody; if AQP4 is positive, reflex to titer; if AQP4 is negative, reflex to MOG antibody; if MOG is positive, reflex to titer. |
CBA |
Diagnose NMOSD and assess prognosis |
|
CSF |
|||
Aquaporin-4 (AQP4) (NMO-IgG) Antibody With Reflex to Titer, CSFa,b |
CBA |
Diagnose NMOSD and assess prognosis |
|
Myelin Oligodendrocyte Glycoprotein (MOG) Antibody With Reflex to Titer, CSFa,b |
CBA |
Diagnose MOGAD and assess need for follow-up testing if low titerc |
|
NMO Spectrum Evaluation (AQP4 With Reflex to MOG), CSFa,b Includes AQP4 antibody; if AQP4 is positive, reflex to titer; if AQP4 is negative, reflex to MOG antibody; if MOG is positive, reflex to titer. |
CBA |
Diagnose NMOSD and assess prognosis |
|
Serum or CSF |
|||
Aquaporin-4 Antibody (IgG), CBAa,d |
CBA |
Diagnose NMOSD and assess prognosis |
|
Aquaporin-4 (AQP4) Antibody (NMO-IgG), ELISAe |
ELISA |
Diagnose NMOSD and assess prognosis |
|
| AQP4, aquaporin-4; CBA, cell-based assay; ELISA, enzyme-linked immunosorbent assay; MOGAD, myelin oligodendrocyte glycoprotein antibody disorder; NMO, neuromyelitis optica; NMOSD, neuromyelitis optica spectrum disorders. | |
| a | This test was developed and its analytical performance characteristics have been determined by Quest. It has not been cleared or approved by FDA. This assay has been validated pursuant to the CLIA regulations and is used for clinical purposes. |
| b | Reflex tests are performed at an additional charge and are associated with an additional CPT code(s). |
| c | Conflicting reports have appeared on whether MOG-Ab titers are predictive of relapse.2,6 |
| d | Serum or CSF specimens are the preferred specimen types. |
| e | CSF specimens are acceptable but serum is preferred. |
Test interpretation [return to contents]
A positive result for AQP4-IgG is consistent with a diagnosis of NMOSD if at least 1 clinical characteristic is present and alternative diagnoses are excluded. This test result is highly specific for the disease and is associated with persistent visual impairment, recurrent attacks, and likelihood of simultaneous optic neuritis and myelitis attacks.8,21 High AQP4 antibody titers are associated with disease activity (high during relapse and low during remission), complete blindness, and cerebral lesions.22,23
A negative result for AQP4-IgG indicates the absence of AQP4 antibodies but does not rule out a diagnosis of NMOSD; other clinical criteria can be met to confirm a diagnosis (Table 1).
A positive result for serum MOG-IgG supports a diagnosis of MOGAD if at least 1 core clinical characteristic is present (ADEM, optical neuritis, transverse myelitis, cerebral monofocal or polyfocal deficits, brainstem or cerebellar deficits, or cerebral cortical encephalitis) and alternative diagnoses are excluded.13 Whether MOG-IgG titers are predictive of relapse is currently unclear2,6 but low titers require other clinical criteria (ie, positive CSF MOG-IgG, AQP4-IgG seronegativity, and ≥1 clinical or MRI features) to confirm a diagnosis.20
A negative result for serum MOG-IgG indicates the absence of MOG antibodies in the serum but does not rule out a diagnosis of MOGAD; other clinical criteria (ie, positive CSF MOG-IgG, AQP4-IgG seronegativity, and ≥1 clinical or MRI features) can be met to confirm a diagnosis.20
References [return to contents]
- Wingerchuk DM, Banwell B, Bennett JL, et al. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology. 2015;85(2):177-189. doi:10.1212/wnl.0000000000001729
- Marignier R, Hacohen Y, Cobo-Calvo A, et al. Myelin-oligodendrocyte glycoprotein antibody-associated disease. Lancet Neurol. 2021;20(9):762-772. doi:10.1016/s1474-4422(21)00218-0
- Demuth S, Collongues N. Disease-modifying treatments for neuromyelitis optica spectrum disorder in the context of a new generation of biotherapies. Rev Neurol. 2025;181(1-2):42-51. doi:10.1016/j.neurol.2024.01.008
- Montalban X, Lebrun-Frénay C, Oh J, et al. Diagnosis of multiple sclerosis: 2024 revisions of the McDonald criteria. Lancet Neurol. 2025;24(10):850-865. doi:10.1016/s1474-4422(25)00270-4
- Ransohoff RM. Illuminating neuromyelitis optica pathogenesis. Proc Natl Acad Sci. 2012;109(4):1001-1002. doi:10.1073/pnas.1119288109
- Dauby S, Dive D, Lutteri L, et al. Comparative study of AQP4-NMOSD, MOGAD and seronegative NMOSD: a single-center Belgian cohort. Acta Neurol Belg. 2022;122(1):135-144. doi:10.1007/s13760-021-01712-3
- Hegen H, Reindl M. Recent developments in MOG-IgG associated neurological disorders. Ther Adv Neurol Disord. 2020;13:1756286420945135. doi:10.1177/1756286420945135
- Sato DK, Callegaro D, Lana-Peixoto MA, et al. Distinction between MOG antibody-positive and AQP4 antibody-positive NMO spectrum disorders. Neurology. 2014;82(6):474-481. doi:10.1212/wnl.0000000000000101
- Gupta S, Rehani V, Dhull P, et al. A comparative analysis of clinical and imaging features of aquaporin 4 (AQP4) antibody positive, myelin oligodendrocyte glycoprotein (MOG) antibody positive and double seronegative subtypes of neuro myelitis optica spectrum disorder (NMOSD). Ann Indian Acad Neurol. 2022;25(2):239-245. doi:10.4103/aian.aian_406_21
- Banks SA, Morris PP, Chen JJ, et al. Brainstem and cerebellar involvement in MOG-IgG-associated disorder versus aquaporin-4-IgG and MS. J Neurol, Neurosurg Psychiatry. 2021;92(4):384-390. doi:10.1136/jnnp-2020-325121
- Valencia-Sanchez C, Guo Y, Krecke KN, et al. Cerebral cortical encephalitis in myelin oligodendrocyte glycoprotein antibody-associated disease. Ann Neurol. 2023;93(2):297-302. doi:10.1002/ana.26549
- Liu K, Wang W, Jin M, et al. FLAIR hyperintense cortical lesions in myelin oligodendrocyte glycoprotein-associated encephalitis with seizures in children: a retrospective single-center case series. Front Immunol. 2025;16:1563481. doi:10.3389/fimmu.2025.1563481
- Moura J, Samões R, Sousa AP, et al. Prognostic factors associated with disability in a cohort of neuromyelitis optica spectrum disorder and MOG-associated disease from a nationwide Portuguese registry. J Neurol Sci. 2024;464:123176. doi:10.1016/j.jns.2024.123176
- Nagireddy RBR, Kumar A, Singh VK, et al. Clinicoradiological comparative study of Aquaporin-4-IgG seropositive neuromyelitis optica spectrum disorder (NMOSD) and MOG antibody associated disease (MOGAD): A prospective observational study and review of literature. J Neuroimmunol. 2021;361:577742. doi:10.1016/j.jneuroim.2021.577742
- Foo R, Yau C, Singhal S, et al. Optic neuritis in the era of NMOSD and MOGAD: a survey of practice patterns in Singapore. Asia-Pac J Ophthalmol. 2022;11(2):184-195. doi:10.1097/apo.0000000000000513
- Kitley J, Waters P, Woodhall M, et al. Neuromyelitis optica spectrum disorders with aquaporin-4 and myelin-oligodendrocyte glycoprotein antibodies: a comparative study. JAMA Neurol. 2014;71(3):276-283. doi:10.1001/jamaneurol.2013.5857
- Devi E, Chandan SK, Rani D, et al. Comparison of clinical and imaging parameters in patients with neuromyelitis optica spectrum disorder and myelin oligodendrocyte glycoprotein antibody-associated disease: a prospective observational study. Cureus. 2025;17(8):e89840. doi:10.7759/cureus.89840
- Du Q, Shi Z, Chen H, et al. Comparison of clinical characteristics and prognoses in patients with different AQP4-Ab and MOG-Ab serostatus with neuromyelitis optica spectrum disorders. J Neuroimmunol. 2021;353:577494. doi:10.1016/j.jneuroim.2021.577494
- Akaishi T, Misu T, Fujihara K, et al. Relapse activity in the chronic phase of anti-myelin-oligodendrocyte glycoprotein antibody-associated disease. J Neurol. 2022;269(6):3136-3146. doi:10.1007/s00415-021-10914-x
- Banwell B, Bennett JL, Marignier R, et al. Diagnosis of myelin oligodendrocyte glycoprotein antibody-associated disease: International MOGAD Panel proposed criteria. Lancet Neurol. 2023;22(Neurology 59 2002):268-282. doi:10.1016/s1474-4422(22)00431-8
- Kezuka T, Usui Y, Yamakawa N, et al. Relationship between NMO-antibody and anti–MOG antibody in optic neuritis. J Neuro-Ophthalmol. 2012;32(2):107-110. doi:10.1097/wno.0b013e31823c9b6c
- Jarius S, Aboul-Enein F, Waters P, et al. Antibody to aquaporin-4 in the long-term course of neuromyelitis optica. Brain. 2008;131(11):3072-3080. doi:10.1093/brain/awn240
- Takahashi T, Fujihara K, Nakashima I, et al. Anti-aquaporin-4 antibody is involved in the pathogenesis of NMO: a study on antibody titre. Brain. 2007;130(5):1235-1243. doi:10.1093/brain/awm062
Content reviewed 11/2025
This Clinical Focus provides an overview of the use of laboratory testing to diagnose and manage neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein antibody disease (MOGAD).
Clinical Focus
NMOSD and MOGAD
Laboratory Support of Diagnosis and Management
Clinical background [return to contents]
Neuromyelitis optica (NMO, also known as Devic’s disease) is an immune-mediated inflammatory disease that predominantly affects the optic nerve and spinal cord. The term NMO spectrum disorders (NMOSD) encompasses limited and early forms of NMO and related conditions. In 2015, NMO and NMOSD were unified under the term NMOSD.1 Myelin oligodendrocyte glycoprotein antibody disease (MOGAD) is a disease with overlapping, but distinct, features compared with NMOSD.2 Accurate diagnosis of these conditions is important because approved targeted treatments for NMOSD have become available and treatments used for conditions with similar symptoms, such as multiple sclerosis (MS), can harm patients with NMOSD.1,3,4
This Clinical Focus discusses how laboratory testing supports diagnosis and management of NMOSD and MOGAD. The material is provided for informational purposes only and is not intended as medical advice. Test selection and interpretation, diagnosis, and patient management decisions should be based on the physician’s education, clinical expertise, and assessment of the patient.
NMOSD
Most patients with NMOSD test positive for antibodies to aquaporin-4 (AQP4, Table 1), a water channel protein responsible for homeostatic balance and clearing waste from the brain among other functions within the central nervous system. The disease more frequently affects women and the age of onset is usually between 30 and 40 years.5
Table 1. Diagnostic Criteria for Neuromyelitis Optica Spectrum Disorders (NMOSD) [return to contents]
Presence of AQP4-IgG1 |
Absence of AQP4-IgG or unknown status1 |
|
|
Core clinical characteristics
|
|
Possible alternative diagnosesb
|
|
| AQP4, aquaporin-4; MRI, magnetic resonance imaging; MOGAD, myelin oligodendrocyte glycoprotein antibody disorder. | |
| a | At least 1 characteristic must be optic neuritis, acute myelitis with longitudinally extensive transverse myelitis (LETM), or area postrema syndrome; dissemination in space; fulfill additional MRI requirements (see reference 1 for details). |
| b | See references 1 and 2 for specific red flags that indicate alternative diagnoses. |
Diagnostic criteria for NMOSD are organized based on the presence or absence of AQP4 IgG antibody. For AQP4 IgG-positive patients, diagnosis requires the presence of at least 1 core clinical characteristic and the exclusion of alternative diagnoses (Table 1). For AQP4 IgG-negative patients and those with unknown AQP4-IgG status, criteria are more stringent. In addition to exclusion of alternative diagnoses, at least 2 clinical characteristics must be present; furthermore, the type and location of the characteristics matter, and additional magnetic resonance imaging (MRI) requirements may need to be met (Table 1).1 Several disease-modifying drugs have been approved for NMOSD for AQP4 IgG-positive patients.3
MOGAD
Most patients with MOGAD test positive for MOG antibodies, which target MOG, a glycoprotein on the outermost myelin membranes surrounding the optic nerves, spinal cord, and brain. Patients with MOGAD tend to be younger6,7 and, as a group, are less predominantly female compared with NMOSD patients who test positive for AQP4 antibodies.2,7–9 The core MOGAD clinical phenotypes include optic neuritis (up to 80% of patients), transverse myelitis (30% to 50%), acute disseminated encephalomyelitis (ADEM, 5% in adults, up to 40% in children), cerebral monofocal or polyfocal deficits, brainstem or cerebellar deficits (up to 34% of patients), and cerebral cortical encephalitis often with seizures (approximately 7%).2,10–12
Overall, patients with MOGAD have milder disease and more favorable outcomes compared with patients with AQP4 antibody-positive NMOSD.7,13–16 For example, a small prospective study conducted over 18 months found less severe clinical attacks and better prognoses among patients with MOGAD (n=15) than among those with AQP4 antibody-positive NMOSD (n=15).17 Compared with AQP4 antibody-positive NMOSD patients, those with MOGAD or double-seronegative NMOSD (negative NMOSD and MOG antibodies) had lower rates of disability and lower expanded disability status.18 Relapse rates tend to be lower in MOGAD compared with NMOSD,6,8,9,19 and patients with MOGAD tend to be more responsive to steroid therapy compared with patients with NMOSD.2,15
Proposed diagnostic criteria for MOGAD consist of 3 requirements: a positive MOG-IgG test, presence of a core clinical phenotype, and the exclusion of an alternative diagnoses such as multiple sclerosis.20 Serum specimens are recommended for all patients undergoing MOG-IgG testing; however, cerebrospinal fluid (CSF) may be valuable in patients with suspected MOGAD but in whom serum testing is negative for MOG-IgG.20 Positive CSF MOG-IgG (and negative serum IgG) or positive serum MOG-IgG but low MOG-IgG titers (or without titers) should be supported with negative AQP4-IgG status and ≥1 clinical or MRI feature.20
Individuals suitable for testing [return to contents]
- Individuals with suspected NMOSD (Table 1) or MOGAD (overlapping clinical features with NMOSD but comparatively more prevalent in younger patients and children with ADEM)
Test availability and selection [return to contents]
Quest Diagnostics offers cell-based assays (CBAs) for testing AQP4 (test code 93893) or MOG antibodies (test code 36952, Table 2) in serum and to assist in differential diagnosis.
CBAs are strongly recommended for AQP4. Tests are also available in CSF. It is rare that a patient’s results for AQP4 in serum will differ from their results in CSF. Therefore, guidelines do not recommend routine CSF testing in AQP4-seronegative patients.1 AQP4 antibody tests are also offered with reflex to titer (test codes 38321 [serum] and 93893 [CSF]).
Enzyme-linked immunosorbent assay (ELISA) testing is also available for AQP4 (test code 90382). However, CBAs have higher sensitivity (77% vs 63%–64% for indirect immunofluorescence or ELISA) and lower false-positive rates (0.1% among MS patients vs 0.5%–1.3% for ELISA).1
A serum CBA is recommended for all patients undergoing MOG-IgG testing, but a CSF MOG-IgG CBA (test code 36954) is available for those with suspected MOGAD who have negative serum test results.20 The MOG antibody tests reflex to titer.
For differential diagnosis, Quest also offers the NMO Spectrum Evaluation in serum (test code 38312) or CSF (test code 38313), which begins with AQP4 testing and reflexes to MOG testing if AQP4 is negative (Table 2).
Table 2. Available Tests for NMOSD and MOGAD [return to contents]
Test code |
Assay |
Method |
Clinical use |
Serum |
|||
Aquaporin-4 (AQP4) (NMO-IgG) Antibody With Reflex to Titer, Seruma,b |
CBA |
Diagnose NMOSD and assess prognosis |
|
Myelin Oligodendrocyte Glycoprotein (MOG) Antibody With Reflex to Titer, Seruma,b |
CBA |
Diagnose MOGAD and assess need for follow-up testing if low titerc |
|
NMO Spectrum Evaluation (AQP4 With Reflex to MOG), Seruma,b Includes AQP4 antibody; if AQP4 is positive, reflex to titer; if AQP4 is negative, reflex to MOG antibody; if MOG is positive, reflex to titer. |
CBA |
Diagnose NMOSD and assess prognosis |
|
CSF |
|||
Aquaporin-4 (AQP4) (NMO-IgG) Antibody With Reflex to Titer, CSFa,b |
CBA |
Diagnose NMOSD and assess prognosis |
|
Myelin Oligodendrocyte Glycoprotein (MOG) Antibody With Reflex to Titer, CSFa,b |
CBA |
Diagnose MOGAD and assess need for follow-up testing if low titerc |
|
NMO Spectrum Evaluation (AQP4 With Reflex to MOG), CSFa,b Includes AQP4 antibody; if AQP4 is positive, reflex to titer; if AQP4 is negative, reflex to MOG antibody; if MOG is positive, reflex to titer. |
CBA |
Diagnose NMOSD and assess prognosis |
|
Serum or CSF |
|||
Aquaporin-4 Antibody (IgG), CBAa,d |
CBA |
Diagnose NMOSD and assess prognosis |
|
Aquaporin-4 (AQP4) Antibody (NMO-IgG), ELISAe |
ELISA |
Diagnose NMOSD and assess prognosis |
|
| AQP4, aquaporin-4; CBA, cell-based assay; ELISA, enzyme-linked immunosorbent assay; MOGAD, myelin oligodendrocyte glycoprotein antibody disorder; NMO, neuromyelitis optica; NMOSD, neuromyelitis optica spectrum disorders. | |
| a | This test was developed and its analytical performance characteristics have been determined by Quest. It has not been cleared or approved by FDA. This assay has been validated pursuant to the CLIA regulations and is used for clinical purposes. |
| b | Reflex tests are performed at an additional charge and are associated with an additional CPT code(s). |
| c | Conflicting reports have appeared on whether MOG-Ab titers are predictive of relapse.2,6 |
| d | Serum or CSF specimens are the preferred specimen types. |
| e | CSF specimens are acceptable but serum is preferred. |
Test interpretation [return to contents]
A positive result for AQP4-IgG is consistent with a diagnosis of NMOSD if at least 1 clinical characteristic is present and alternative diagnoses are excluded. This test result is highly specific for the disease and is associated with persistent visual impairment, recurrent attacks, and likelihood of simultaneous optic neuritis and myelitis attacks.8,21 High AQP4 antibody titers are associated with disease activity (high during relapse and low during remission), complete blindness, and cerebral lesions.22,23
A negative result for AQP4-IgG indicates the absence of AQP4 antibodies but does not rule out a diagnosis of NMOSD; other clinical criteria can be met to confirm a diagnosis (Table 1).
A positive result for serum MOG-IgG supports a diagnosis of MOGAD if at least 1 core clinical characteristic is present (ADEM, optical neuritis, transverse myelitis, cerebral monofocal or polyfocal deficits, brainstem or cerebellar deficits, or cerebral cortical encephalitis) and alternative diagnoses are excluded.13 Whether MOG-IgG titers are predictive of relapse is currently unclear2,6 but low titers require other clinical criteria (ie, positive CSF MOG-IgG, AQP4-IgG seronegativity, and ≥1 clinical or MRI features) to confirm a diagnosis.20
A negative result for serum MOG-IgG indicates the absence of MOG antibodies in the serum but does not rule out a diagnosis of MOGAD; other clinical criteria (ie, positive CSF MOG-IgG, AQP4-IgG seronegativity, and ≥1 clinical or MRI features) can be met to confirm a diagnosis.20
References [return to contents]
- Wingerchuk DM, Banwell B, Bennett JL, et al. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology. 2015;85(2):177-189. doi:10.1212/wnl.0000000000001729
- Marignier R, Hacohen Y, Cobo-Calvo A, et al. Myelin-oligodendrocyte glycoprotein antibody-associated disease. Lancet Neurol. 2021;20(9):762-772. doi:10.1016/s1474-4422(21)00218-0
- Demuth S, Collongues N. Disease-modifying treatments for neuromyelitis optica spectrum disorder in the context of a new generation of biotherapies. Rev Neurol. 2025;181(1-2):42-51. doi:10.1016/j.neurol.2024.01.008
- Montalban X, Lebrun-Frénay C, Oh J, et al. Diagnosis of multiple sclerosis: 2024 revisions of the McDonald criteria. Lancet Neurol. 2025;24(10):850-865. doi:10.1016/s1474-4422(25)00270-4
- Ransohoff RM. Illuminating neuromyelitis optica pathogenesis. Proc Natl Acad Sci. 2012;109(4):1001-1002. doi:10.1073/pnas.1119288109
- Dauby S, Dive D, Lutteri L, et al. Comparative study of AQP4-NMOSD, MOGAD and seronegative NMOSD: a single-center Belgian cohort. Acta Neurol Belg. 2022;122(1):135-144. doi:10.1007/s13760-021-01712-3
- Hegen H, Reindl M. Recent developments in MOG-IgG associated neurological disorders. Ther Adv Neurol Disord. 2020;13:1756286420945135. doi:10.1177/1756286420945135
- Sato DK, Callegaro D, Lana-Peixoto MA, et al. Distinction between MOG antibody-positive and AQP4 antibody-positive NMO spectrum disorders. Neurology. 2014;82(6):474-481. doi:10.1212/wnl.0000000000000101
- Gupta S, Rehani V, Dhull P, et al. A comparative analysis of clinical and imaging features of aquaporin 4 (AQP4) antibody positive, myelin oligodendrocyte glycoprotein (MOG) antibody positive and double seronegative subtypes of neuro myelitis optica spectrum disorder (NMOSD). Ann Indian Acad Neurol. 2022;25(2):239-245. doi:10.4103/aian.aian_406_21
- Banks SA, Morris PP, Chen JJ, et al. Brainstem and cerebellar involvement in MOG-IgG-associated disorder versus aquaporin-4-IgG and MS. J Neurol, Neurosurg Psychiatry. 2021;92(4):384-390. doi:10.1136/jnnp-2020-325121
- Valencia-Sanchez C, Guo Y, Krecke KN, et al. Cerebral cortical encephalitis in myelin oligodendrocyte glycoprotein antibody-associated disease. Ann Neurol. 2023;93(2):297-302. doi:10.1002/ana.26549
- Liu K, Wang W, Jin M, et al. FLAIR hyperintense cortical lesions in myelin oligodendrocyte glycoprotein-associated encephalitis with seizures in children: a retrospective single-center case series. Front Immunol. 2025;16:1563481. doi:10.3389/fimmu.2025.1563481
- Moura J, Samões R, Sousa AP, et al. Prognostic factors associated with disability in a cohort of neuromyelitis optica spectrum disorder and MOG-associated disease from a nationwide Portuguese registry. J Neurol Sci. 2024;464:123176. doi:10.1016/j.jns.2024.123176
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Content reviewed 11/2025