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Neuromyelitis Optica, IgG Autoantibodies

CPT: 83520
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  • Aquaporin-4
  • NMO IgG

Expected Turnaround Time

3 - 5 days

Related Documents

Specimen Requirements




0.2 mL


Red-top tube or gel-barrier tube


If a red-top tube is used, transfer separated serum to a plastic transport tube.

Storage Instructions


Stability Requirements



Room temperature

24 hours


14 days


14 days

Freeze/thaw cycles

Stable x3

Causes for Rejection

Gross lipemia; gross hemolysis; gross icterus

Test Details


Establishing the diagnosis of neuromyelitis optica (NMO) and related disorders, including relapsing transverse myelitis or relapsing optic neuritis. Distinguishing NMO and NMO spectrum disorders from multiple sclerosis early in the course of disease. This test can also be used to trigger initiation and monitor effectiveness of therapy.


Seronegativity does not exclude the diagnosis of NMO.1 Immunosuppressive therapy may result in negative results.


Enzyme-linked immunosorbent assay (ELISA)

Reference Interval

• 0−3.0 U/mL = negative

• >3.0 = positive

Additional Information

Neuromyelitis optica (NMO), also known as Devic's disease, is an immune-mediated neurologic disorder that causes very severe, often bilateral, optic neuritis and longitudinally extensive spinal cord lesions.2,3 Historically, NMO was thought to be a form of multiple sclerosis;3 however, the nerve damage suffered by patients with NMO has been shown to be distinct from that found in patients with multiple sclerosis.2-4 Patients with NMO can present with a variety of symptoms, including visual impairment, muscle weakness, reduced peripheral sensation, and loss of bladder and/or bowel control.5 NMO typically follows a relapsing course without marked remission between flare-ups. Neural damage tends to be cumulative, resulting in rapid progression of disability and the development of irreversible deficits.6

Recently, antibodies to the most abundant water channel in the central nervous system, aquaporin-4 (AQP4), have been found in patients with NMO.1 These antibodies, referred to as AQP4-Ab or NMO-Ab, have been detected in 60% to 90% of patients with NMO and have been shown to correlate with NMO disease activity.1,3 NMO-Ab have also been observed in some patients with limited forms of the disease (NMO spectrum disorders), including longitudinally extensive transverse myelitis (LETM) and isolated optic neuritis. Studies have demonstrated that injection of NMO-Ab-positive serum into animals or cultured cells expressing AQP4 produces a disruption of the blood-brain barrier, impairment of glutamate homeostasis, and induction of necrotic cell death.3 These studies suggest a direct role of NMO-Ab in the pathogenesis of NMO.

Immunoassays employing a variety of different immunological techniques for the detection of NMO-Ab in patients with NMO have been described.3 Wingerchuk and associates have proposed a set of criteria for the diagnosis of neuromyelitis optica that incorporate the assessment of NMO-Ab status.7 This guideline suggests that the diagnosis of NMO requires two absolute criteria (optic neuritis and acute myelitis) plus at least two of three supportive criteria, one of which is NMO-Ab seropositive status. Measurement of NMO-Ab can be of value in distinguishing NMO from MS when full clinical features may not be apparent and early intervention may prevent or delay disability. Early diagnosis of NMO is critical for avoiding the cumulative effects that result in progressive disability. A positive value is consistent with NMO or a related disorder and helps justify initiation of appropriate therapy.

Four hundred thirty-three samples routinely submitted for NMO-Ab testing were tested by both the aquaporin-4 autoantibody ELISA and indirect immunofluorescence assay (IFA) performed at Mayo Clinic Laboratory.8 98.1% of results were in agreement with a positive result agreement of 78.6% and negative result agreement of 98.8% (IFA as reference method). These results are comparable to those observed in a previously published study comparing an ELISA to IFA for diagnosing NMO.9


1. Lennon VA, Wingerchuk DM, Kryzer TJ, et al. A serum autoantibody marker of neuromyelitis optica: Distinction from multiple sclerosis. Lancet . 2004 Dec 11-17; 364(9451):2106-2112. 15589308
2. Pittock SJ, Weinshenker BG, Lucchinetti CF, Wingerchuk DM, Corboy JR, Lennon VA. Neuromyelitis optica brain lesions localized at sites of high aquaporin 4 expression. Arch Neurol. 2006 Jul; 63(7):964-968. 16831965
3. Jarius S, Wildemann B. AQP4 antibodies in neuromyelitis optica: Diagnostic and pathogenic relevance. Nat Rev Neurol. 2010 Jul; 6(7):383-392. 20639914
4. Nakajima H, Hosokawa T, Sugino M, et al. Visual field defects of optic neuritis in neuromyelitis optica compared with multiple sclerosis. BMC Neurol. 2010 Jun 18; 10:45. 20565857
5. Pittock SJ, Lennon VA, Krecke K, Wingerchuk DM, Lucchinetti CF, Weinshenker BG. Brain abnormalities in neuromyelitis optica. Arch Neurol. 2006 Mar; 63(3):390-396. 16533966
6. Jacob A, Matiello M, Weinshenker BG, et al. Treatment of neuromyelitis optica with mycophenolate mofetil: Retrospective analysis of 24 patients. Arch Neurol. 2009 Sep; 66(9):1128-1133. 19752302
7. Wingerchuk DM, Lennon VA, Pittock SJ, Lucchinetti CF, Weinshenker BG. Revised diagnostic criteria for neuromyelitis optica. Neurology. 2006 May 23; 66(10):1485-1489. 16717206
8. Internal study performed at the Center for Esoteric Testing, LabCorp, Burlington, NC.
9. Hayakawa S, Mori M, Okuta A, et al. Neuromyelitis optica and anti-aquaporin-4 antibodies measured by an enzyme-linked immunosorbent assay. J Neuroimmunology. 2008 May 30; 196(1-2):181-187. 18462810


Order Code Order Code Name Order Loinc Result Code Result Code Name UofM Result LOINC
004210 NMO IgG Autoantibodies 61430-5 004213 NMO IgG Autoantibodies U/mL 61430-5

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