Diagnosis of inflammatory demyelinating diseases (IDD) with similar phenotype to neuromyelitis optica (NMO) spectrum disorder (NMOSD), including optic neuritis (single or bilateral) and transverse myelitis
Diagnosis of autoimmune myelin oligodendrocyte glycoprotein (MOG)-opathy
Diagnosis of NMO
Distinguishing NMOSD, acute disseminated encephalomyelitis (ADEM), optic neuritis, and transverse myelitis from multiple sclerosis early in the course of disease
Diagnosis of ADEM
Prediction of a relapsing disease course
Myelin oligodendrocyte glycoprotein (MOG)-IgG with neuromyelitis optica (NMO) spectrum disorder (SD)-like phenotype is now recognized as a sensitive and specific diagnostic antibody biomarker of inflammatory demyelinating disorders (IDD).
Approximately 80% of patients fulfilling 2006 Wingerchuk criteria for NMO are seropositive for aquaporin-4 (AQP4)-IgG. Of the remaining 20%, one-third harbor MOG-IgG. Seropositivity predicts a relapsing phenotype and warrants immunosuppressive therapy. Patients only rarely harbor both antibodies.
There is currently no biomarker specific for MS (multiple sclerosis). Patients seropositive for MOG-IgG are commonly misdiagnosed as MS. Detection of MOG-IgG implies an inflammatory demyelinating disorder distinct from MS. MS therapies may worsen MOG-IgG associated IDD, so correct diagnosis is important.
Seropositivity for MOG-IgG in NMOSD-like disorders, including optic neuritis, transverse myelitis, and acute disseminated encephalomyelitis, predicts relapse and warrants consideration for maintenance immunosuppression.
Seropositivity for MOG-IgG in the setting of a severe relapse of central nervous system demyelination warrants aggressive therapy with intravenous methylprednisolone or plasmapheresis.
| Test Id | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| MOGTS | MOG FACS Titer, S | No | No |
When the results of this assay require further evaluation, the reflex titer test will be performed at an additional charge.
Flow Cytometry
MOG-IgG
MOG
Optic Neuritis Antibody
Transverse Myelitis Antibody
Vision Loss Antibody
ADEM antibody
NMO antibody
When the results of this assay require further evaluation, the reflex titer test will be performed at an additional charge.
Serum
Patient Preparation: For optimal antibody detection, specimen collection should occur prior to initiation of immunosuppressant medication.
Collection Container/Tube:
Preferred: Red top
Acceptable: Serum gel
Submission Container/Tube: Plastic vial
Specimen Volume: 2 mL
Collection Instructions: Centrifuge and aliquot serum into a plastic vial.
If not ordering electronically, complete, print, and send 1 of the following with the specimen:
-Neurology Specialty Testing Client Test Request (T732)
-General Request (T239)
1 mL
| Gross hemolysis | Reject |
| Gross lipemia | Reject |
| Gross icterus | Reject |
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Serum | Refrigerated (preferred) | 28 days | |
| Frozen | 28 days | ||
| Ambient | 72 hours |
Diagnosis of inflammatory demyelinating diseases (IDD) with similar phenotype to neuromyelitis optica (NMO) spectrum disorder (NMOSD), including optic neuritis (single or bilateral) and transverse myelitis
Diagnosis of autoimmune myelin oligodendrocyte glycoprotein (MOG)-opathy
Diagnosis of NMO
Distinguishing NMOSD, acute disseminated encephalomyelitis (ADEM), optic neuritis, and transverse myelitis from multiple sclerosis early in the course of disease
Diagnosis of ADEM
Prediction of a relapsing disease course
When the results of this assay require further evaluation, the reflex titer test will be performed at an additional charge.
Neuromyelitis optica (NMO), sometimes called Devic disease or opticospinal multiple sclerosis (MS) is a severe, relapsing, autoimmune, inflammatory and demyelinating central nervous system disease (IDD) that predominantly affects optic nerves and spinal cord.(1) The disorder is now recognized as a spectrum of autoimmunity (termed NMO spectrum disorders: NMOSD).(1-3) Brain lesions are observed in more than 60% of patients with NMOSD and approximately 10% will be MS-like.(4) Children tend to have greater brain involvement than adults, and brain lesions are more symptomatic than is typical for adult patients.(3) The clinical course is characterized by relapses of optic neuritis or transverse myelitis or both. Some patients may present with acute disseminated encephalomyelitis (ADEM). Many patients with NMOSD are misdiagnosed as having MS. More effective treatments combined with earlier and more accurate diagnosis has led to improved outcomes.
Approximately 80% of patients with NMO are seropositive for aquaporin-4 (AQP4)-IgG.(5-7) In the remaining 20% of patients, myelin oligodendrocyte glycoprotein (MOG)-IgG is detected in up to a third.(8) The pathogenic target for the remaining patients remains unknown. Detection of MOG-IgG is diagnostic of central nervous system (CNS) inflammatory demyelination, where the clinical phenotype (NMOSD, optic neuritis, transverse myelitis, ADEM) may be similar, but the immunopathology (astrocytopathy vs oligodendrogyopathy) and clinical outcome (worse vs better) are different.(9) Detection of MOG-IgG also predicts relapse.(10) More importantly, MOG-IgG seropositive IDDs are distinct from MS and treated differently.(8, 9) Treatments for IDDs seropositive for MOG-IgG include corticosteroids and plasmapheresis for acute attacks and mycophenolate mofetil, azathioprine, and rituximab for relapse prevention. Disease-modifying agents, treatments promoted for MS, have been reported to exacerbate MOG-IgG1 seropositive IDDs. Therefore, early diagnosis and initiation of appropriate immunosuppressant treatment is important to optimize the clinical outcome by preventing further attacks. In 2015, Waters and colleagues (11) from Oxford University established a novel cell-based assay for the measurement of IgG1 MOG antibodies based on previous findings that MOG antibodies are almost exclusively of the IgG1 subclass. They showed that their MOG-IgG1 flow cytometry assay eliminated false positive results without losing true positive results with low titers. The detection of MOG-IgG1 allowed non-MS demyelinating diseases (ADEM, AQp4-IgG negative neuromyelitis optica spectrum disorder including ON,TM) to be distinguished from MS.(12)
Using a similar assay to this MOG-IgG1 flow cytometry assay, demonstrated high specificity of their MOG-IgG1 assay in which 49 patients with MS, 13 healthy control sera, and 37 AQP4-seropositive serum samples were all negative at a dilution of 1:20. Of 58 patients fulfilling 2006 Wingerchuk criteria for NMO, 21 (36%) tested negative for AQP4-IgG. MOG-IgG1 was detected by cell-based assay in 8 (38%) of these cases.(13)
Testing of 1109 consecutive sera sent for AQP4-IgG testing(12) revealed 40 AQP4-IgG and 65 MOG-IgG1-positive cases. None were positive for both. The clinical diagnoses obtained in 33 MOG-IgG1-positive patients included 4 NMO, 1 ADEM, and 11 optic neuritis (n = 11). All 7 patients with probable MS were MOG-IgG1 negative. This study provides Class II evidence that the presence of serum MOG-IgG1 distinguishes non-MS CNS demyelinating disorders from MS (sensitivity 24%, 95% CI 9%-45%; specificity 100%, 95% CI 88%-100%).
This assay was developed using the MOG construct provided by Dr Waters,(11) and the validation was based on a blinded comparison with the Oxford assay. Comparison was also made with the Euroimmun fixed cell-based kit assay.(14)
A recent longitudinal analysis with 2-year follow-up suggested that persistence of MOG-IgG is associated with relapses thus warranting relapse prevention.(10) Detection of MOG-IgG1 allows distinction from MS and is generally indicative of a relapsing disease, mandating initiation of immunosuppression, even after the first attack in some, thereby reducing attack frequency and disability in the future.
Negative
A positive value for myelin oligodendrocyte glycoprotein (MOG)-IgG is consistent with a neuromyelitis optica-like phenotype and, in the setting of acute disseminated encephalomyelitis, optic neuritis and transverse myelitis, indicates an autoimmune oligodendrogliopathy with potential for relapsing course. Identification of MOG-IgG allows distinction from multiple sclerosis (MS) and may justify initiation of appropriate immunosuppressive therapy (not MS disease-modifying agents) at the earliest possible time. This allows early initiation and maintenance of optimal therapy. Recommend follow-up in 6 to 12 months, as persistence of MOG-IgG seropositivity predicts a relapsing course.
This autoantibody is not found in healthy subjects.
Myelin oligodendrocyte glycoprotein (MOG)-IgG, specifically MOG-IgG1, may drop below detectable levels in setting of therapies for acute attack (IV methylprednisolone or plasmapheresis) or attack prevention (immunosuppressants).
1. Wingerchuk DM, Lennon VA, Lucchinetti CF, et al. The spectrum of neuromyelitis optica. Lancet Neurol. 2007;6(9):805-815
2. Apiwattanakul M, Popescu BF, Matiello M, et al. Intractable vomiting as the initial presentation of neuromyelitis optica. Ann Neurol. 2010;68(5):757-761
3. McKeon A, Lennon VA, Lotze T, et al. CNS aquaporin-4 autoimmunity in children. Neurology 2008;71(2):93-100
4. Pittock SJ, Weinshenker BG, Lucchinetti CF, et al. Neuromyelitis optica brain lesions localized at sites of high aquaporin 4 expression. Arch Neurol. 2006;63(7):964-968
5. Fryer JP, Lennon VA, Pittock SJ, et al. AQP4 autoantibody assay performance in clinical laboratory service. Neurol Neuroimmunol Neuroinflamm. 2014;1(1):e11
6. Waters PJ, McKeon A, Leite MI, et al. Serologic diagnosis of NMO: a multicenter comparison of aquaporin-4-IgG assays. Neurology. 2012;78(9):665-669
7. Lennon VA, Wingerchuk DM, Kryzer TJ, et al. A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet. 2004;364(9451):2106-2112
8. Peschl P, Bradl M, Hoftberger R, et al. Myelin oligodendrocyte glycoprotein: deciphering a target in inflammatory demyelinating diseases. Front Immunol. 2017;8:529
9. Pittock SJ, Lucchinetti CF. Neuromyelitis optica and the evolving spectrum of autoimmune aquaporin-4 channelopathies: a decade later. Ann NY Acad Sci. 2016;1366(1):20-39
10. Hyun JW, Woodhall MR, Kim SH, et al. Longitudinal analysis of myelin oligodendrocyte glycoprotein antibodies in CNS inflammatory diseases. J Neurol Neurosurg Psychiatry. 2017;88(10):811-817
11. Waters P, Woodhall M, O'Connor KC, et al. MOG cell-based assay detects non-MS patients with inflammatory neurologic disease. Neurol Neuroimmunol Neuroinflamm. 2015;2(3):e89
12. Reindl M, Jarius S, Rostasy K, Berger T. Myelin oligodendrocyte glycoprotein antibodies: How clinically useful are they? Curr Opin Neurol. 2017;30(3):295-301
13. Wingerchuk DM, Banwell B, Bennett JL, et al. International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology. 2015;85(2):177-189
14. Jarius S, Ruprecht K, Kleiter I, et al. MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 1: Frequency, syndrome specificity, influence of disease activity, long-term course, association with AQP4-IgG, and origin. J Neuroinflammation. 2016;13(1):279
MOG-IgG1 Fluorescence-Activated Cell-Sorting Assay
Human embryonic kidney cells (HEK 293) are transfected transiently with a DNA plasmid that allows coexpression of both a reporter fluorescent protein (green fluorescent protein: AcGFP) and full-length MOG. After 36 hours, a mixed population of cells (transfected expressing MOG on the surface and AcGFP in the cytoplasm and nontransfected lacking MOG and AcGFP) are lifted and resuspended in live cell-binding buffer. Cells are incubated with patient serum, and an AlexaFluor 647-labeled secondary antibody is added. Two populations are gated based on AcGFP expression: positive (high MOG expression) and negative (low or no MOG expression). Positivity is based on the ratio (positive >2.5) of the median fluorescence intensity (MFI) of each cell population (MFI GFP positive:MFI GFP negative).(Unpublished Mayo method)
If MOG-IgG1 cell-based flow cytometry (fluorescence-activated cell-sorting assay: FACS) assay is positive at screening dilution, the MOG-IgG1 flow cytometry titer assay is performed at an additional charge.(Unpublished Mayo method)
Monday, Tuesday, Thursday
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.
86363
86363-titer (if appropriate)
| Test Id | Test Order Name | Order LOINC Value |
|---|---|---|
| MOGFS | MOG FACS, S | 90248-6 |
| Result Id | Test Result Name |
Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
|
|---|---|---|
| 65563 | MOG FACS, S | 90248-6 |