Myelin Oligodendrocyte Glycoprotein (MOG) Antibody Evaluation

Neurology

NMOSD

Diagnose Neuromyelitis Optica

Spectrum Disorder sooner

Uncovering new clinical insights from MOG antibody testing

Recent research and advances in technology have led to a better understanding of the role antibodies play in diagnosis, treatment, and prognosis of central nervous system disorders.

Identifying antibodies that are contributing factors in diseases, such as Neuromyelitis Optica Spectrum Disorder (NMOSD), allows physicians to provide patients a clear diagnosis and implement an appropriate treatment regimen designed to reduce the risk of relapse.

Researchers have now discovered one particular antibody—Myelin Oligodendrocyte Glycoprotein (MOG)—that can be present in NMOSD and other autoimmune disorders. The new MOG antibody evaluation from Athena Diagnostics may help physicians and their patients navigate through the complexity of NMOSD on a streamlined path to a diagnosis.

What is NMOSD?

NMOSD is an immune-mediated chronic, often relapsing, inflammatory disease that predominantly affects the optic nerve and spinal cord.1 It can sometimes be mistaken for MS, because many of the symptoms overlap between the two diseases.

• NMOSD attacks generally have a sudden, severe onset, causing immediate disability, including blindness and paralysis

• MS episodes tend to be mild, especially in the early stages of the disease

• Patients with NMOSD often simultaneously present with optic neuritis and transverse myelitis1

• NMOSD is generally mediated by anti-aquaporin (AQP4) antibodies. An AQP4 test is generally negative in MS patients.2

The limitations of AQP4 antibody testing

Based upon the patient’s clinical presentation, testing for AQP4 is generally recognized as the first path to a diagnosis. A high AQP4 reading may indicate a more aggressive therapy is needed to prevent a relapse.

However, AQP4 is not the only antibody that can play a role in NMOSD. A growing body of research indicates that 10%–50% of patients with NMOSD still test negative for AQP4,3 and 15%–35% of these patients end up testing positive for MOG antibodies.1,4,5,6

“In almost half of cases what we think is the likely underlying antibody cause of a given syndrome is not the antibody we find…”

— Stanley J. Naides, MD, FACP, FACR Medical Director, Immunology R&D, Quest Diagnostics

MOG Antibody Evaluation

MOG-antibody positive and AQP4-antibody positive patients present differently

MOG-positive patients generally present with a different clinical phenotype than patients with AQP4 antibodies.5

• More frequently male

• Had more bilateral, simultaneous optic neuritis attacks

• More often had a single attack

• Lower disability range via Expanded Disability Status Scale (EDSS)

• Lack of nausea/vomiting episode

• Patients with MOG antibodies usually have a better outcome than AQP4-positive patients.8

MOG antibodies in NMOSD patients

While an understanding of MOG’s role in humans is still relatively new, the antibody can be present in a number of central nervous system inflammatory diseases, including NMOSD, acute disseminated encephalomyelitis (ADEM), and adult and pediatric MS.8 The NMOSD phenotype is most commonly observed in patients with MOG antibodies.

MOG antibodies are a component of myelin proteins in the central nervous system, predominantly located in the outermost surface of myelin sheaths and serving as a biologically accessible antigenic target for circulating antibodies.9

While the percentage of patients with MOG antibodies in comparison to AQP4 antibodies remains around 10%, anti-MOG antibodies can serve as a diagnostic tool in patients with an AQP4-negative NMOSD phenotype, and these patients should be tested in accordance with the patient’s clinical presentation.

Test for AQP4

NMOSDDiagnosis

Suspect NMOSD

Test is negativeCheck for:

Test is negativeRe-evaluate patient’s symptoms and consider alternative diagnosis

Test is positive

Test for MOGThe presence of at least two of the following characteristics:• Optic neuritis• Acute myelitis• Area postrema syndrome• Acute brainstem syndrome• Symptomatic narcolepsy or

acute diencephalic clinical syndrome with NMOSD-typical diencephalic MRI lesions

• Symptomatic cerebral syndrome with NMOSD-typical brain lesions

Must also have thefollowing:• At least one core clinical

characteristic must be optic neuritis, acute myelitis with longitudinally extensive transverse myelitis (LETM), or area postrema syndrome

• Dissemination in space(two or more different core clinical characteristics)

• Fulfillment of additional MRI requirements, as applicable

Negative tests for AQP4 using best available detection method, or testing is unavailable

Exclusion of alternative diagnosis

Test is positiveReflex to titer

Diagnostic criteria for NMOSD without AQP4 or NMOSD with unknown AQP4-IgG status7

MOG antibody testing can provide insightNo one clinical characteristic is exclusive to NMOSD,7 so it can be difficult to make a definitive diagnosis. The patient’s presentation is the first step to an accurate diagnosis. Once their clinical symptoms have been reviewed, consider testing for AQP4 and MOG antibodies in the quest for an accurate diagnosis of NMOSD.

References1. 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. 2. Kim SM, Kim SJ, Lee HJ, et al. Differential diagnosis of neuromyelitis optical spectrum disorders. Ther Adv Neurol Disord. 2017;10(7):265-289. 3. Pröbstel AK, Rudolf G, Dornmair K, et al. Anti-MOG antibodies are present in a subgroup of patients with a neuromyelitis optica phenotype. J Neuroinflammation. 2015;12:46. doi: 10.1186/s12974-015-0256-1. 4. Kezuka T, Usui Y, Yamakawa N, et al. Relationship between NMO-antibody and anti-MOG antibody in optic neuritis. J Neuroophthalmol. 2012;32(2):107-110. doi: 10.1097/WNO.0b013e31823c9b6c. 5. 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. 6. 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. doi: 10.1212/NXI. 0000000000000089. eCollection 2015 Jun. 7. Wingerchuck 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. 8. Höftberger R, Sepulveda M, Armangue T, et al. Antibodies to MOG and AQP4 in adults with neuromyelitis optica and suspected limited forms of the disease. Mult Scler. 2015;21(7):866-874. doi: 10.1177/13524585514555785. 9. 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. doi: 10.1136/jnnp-2017-315998.

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Athena Diagnostics offers a comprehensive test menu for autoimmune diseases through every stage of care: screening, diagnosis, monitoring, and progress. Contact us by phone at 1.800.394.4493.

Test ordering information for MOG Antibody

Test code Test name CPT

code(s)*

Serum, red-top tube (no additives) or SST® Serum Separation Tubes

Turnaround time

Specimen Stability

Ambient Refrigerated Frozen

1523MOG Antibody Evaluation with reflex to titer

86255

Preferred: 2.5 mL(0.5mL minimum) serumAlternate: 2 mL (0.5 mL minimum) CSFCSF should be collected in plastic screw cap vials.

3–7 days 3 days 45 days 39 days

1287NMO Spectrum Evaluation (AQP4, CBA reflex to MOG, CBA)

86255 reflex to 86255

Preferred: 2 mL (0.5 mL minimum) serum Alternate: 2 mL (0.5 mL minimum) CSFCSF should be collected in plastic screw cap vials.

7–14 days 72 hours 30 days 30 days

1284NMO Spectrum Evaluation (AQP4, ELISA reflex to MOG, CBA)

83516 reflex to 86255

Preferred: 2 mL (0.5 mL minimum) serum 7–14 days 72 hours 40 days 39 days

1282Aquaporin-4 (AQP4) (NMO-IgG) Antibody, CBA with reflex to titer

86255

Preferred: 2 mL (0.5 mL minimum) serum Alternate: 2 mL (0.5 mL minimum) CSFCSF should be collected in plastic screw cap vials.

3–7 days 72 hours 30 days 30 days

193Aquaporin-4 (AQP4) (NMO-IgG) Antibody, ELISA

83516 Preferred: 2 mL (0.5 mL minimum) serum 5–7 days 72 hours 40 days 5 months

Special Transport Requirements: Samples may be shipped frozen, refrigerated, or at ambient temperatureComponents of panel — Myelin Oligodendrocyte Glycoprotein (MOG) Antibody, CBA

* The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

The MOG Antibody Evaluation streamlines the path to diagnosis and treatment

The MOG Antibody Evaluation from Athena Diagnostics delivers clear, positive identification that can help you definitively diagnose NMOSD and treat patients sooner.

Early diagnosis is critical, because treatments such as interferon-beta, natalizumab, fingolimod, and alemtuzumab that are effective for MS or other demyelinating disorders might be ineffective or even harmful for patients with NMOSD. Research shows that 87% of patients experienced good

recovery following a high dose of corticosteroid medications, the recommended therapy for NMOSD patients.5

A rapid turnaround is critical, allowing physicians to establish an effective treatment protocol that may halt the recurrence of debilitating symptoms. When used in conjunction with other clinical testing, the MOG Antibody Evaluation can help physicians make an informed diagnosis and improve patient outcomes.