Myelin Associated Glycoprotein (MAG) IgM Autoantibodies

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Special Instructions

This assay is not approved for patients of New York State physicians.


Expected Turnaround Time

7 days


Related Documents


Specimen Requirements


Specimen

Serum, frozen


Volume

0.3 mL


Minimum Volume

0.1 mL (Note: This volume does not allow for repeat testing.)


Container

Gel-barrier tube or red-top tube


Collection

Separate serum from cells. Transfer the serum into a LabCorp PP transpak frozen purple tube with screw cap (LabCorp No. 49482). Freeze immediately and maintain frozen at ≤ -20°C until tested. To avoid delays in turnaround time when requesting multiple tests on frozen samples, please submit separate frozen specimens for each test requested.


Storage Instructions

Freeze


Stability Requirements

Temperature

Period

Frozen

1 year (stability determined by manufacturer or literature reference)

Freeze/thaw cycles

Stable x2 (stability determined by manufacturer or literature reference)


Patient Preparation

Lipemic samples can be avoided by having the patient fast for 12 hours prior to collection.


Causes for Rejection

Non-serum sample received; non-frozen serum received; grossly lipemic, hemolytic or icteric sample received; cryoglobulin present


Test Details


Use

The BUHLMANN Anti-MAG™ ELISA is intended for the quantitative in vitro diagnostic determination of human IgM autoantibodies directed against Myelin Associated Glycoprotein (MAG).1


Limitations

Results of this test are labeled for research purposes only by the assay's manufacturer. The performance characteristics of this assay have not been established by the manufacturer. The result should not be used for treatment or for diagnostic purposes without confirmation of the diagnosis by another medically established diagnostic product or procedure. The performance characteristics were determined by LabCorp.


Methodology

BUHLMANN™ anti-MAG ELISA. This assay measures antibodies to purified human MAG.1,2,12-25


Reference Interval

0-999 BTU


Additional Information

MAG is a transmembrane lectin that preferentially binds to alpha-2,3-linked sialic acid terminal carbohydrates on cell surface molecules. It is localized in the oligodendroglial membranes of myelin sheaths and Schwann cells. Several different forms of motor and sensory neuropathies are associated with antibodies against the sulphated glucuronic acid moieties of MAG. The clinical picture of anti-MAG neuropathy is characterized by a distal and symmetric, mostly sensory neuropathy.2-6 The clinical course of anti- MAG neuropathy is usually slowly progressive with evidence of demyelination and a variable degree of axonal loss associated with gait ataxia.7 However, the clinical presentation of these patients can be variable, suggesting autoimmunity to other components of myelin may play a role in the disease.8

Anti-MAG autoantibodies frequently occur with IgM paraproteinemia. Approximately half the patients with Monoclonal Gammopathy of Uncertain Significance (MGUS) of IgM type with peripheral neuropathies have antibodies against MAG.2,6 Anti-MAG IgM has also been identified in Waldenstrom's macroglobulinemia and IgM secreting lymphoma. These MAG autoantibodies are believed to be pathogenic.2,9 A joint task force of the European Federation of Neurological Societies (EFNS) and Peripheral Nerve Society (PNS) have constructed clinically useful guidelines for the diagnosis, investigation and treatment of patients with both, a demyelinating neuropathy and a paraprotein.10

Patients with anti-MAG antibodies may respond favorably to therapeutic intervention but to date there is no consensus on the treatment of this disease.2,11,12 Testing for the presence of these autoantibodies is useful for diagnosis as well as for monitoring of therapy.13,14 Historically, clinicians have applied a variety of approaches to treatment of anti-MAG neuropathy including:

• Reduction of circulating IgM anti-MAG antibodies by removal by [plasma exchange],

• Inhibition with Intravenous Immunoglobulin (IVIg), or

• Reduction of their synthesis by corticosteroids, immunosuppressive agents, cytotoxic agents or interferon alpha.9,15

Recent reports suggest Rituximab may be effective in some patients with anti-MAG neuropathy.4,7,16-20 However, the effectiveness of this approach has not been confirmed in all cases.12,21,22


Footnotes

1. Anti-MAG Elisa [package insert]. Switzerland: BUHLMANN Labs; Nov. 16, 2012.
2. Franciotta D, Gastaldi M, Benedetti L, et al. Diagnostics of anti-MAG antibody polyneuropathy. Neurol Sci. 2017 Oct;38(Suppl 2):249-252.29030772
3. Lozeron P, Ribrag V, Adams D, et al. Is distal motor and/or sensory demyelination a distinctive feature of anti-MAG neuropathy? J Neurol. 2016 Sep;263(9):1761-1770.27314957
4. Campagnolo M, Ferrari S, Dalla Torre C, et al. Polyneuropathy with anti-sulfatide and anti-MAG antibodies: clinical, neurophysiological, pathological features and response to treatment. J Neuroimmunol. 2015 Apr 15;281:1-4.25867460
5. Quarles RH. Myelin-associated glycoprotein (MAG): past, present and beyond. J Neurochem. 2007 Mar;100(6):1431-1448.17241126
6. Pruppers MHJ, Merkies ISJ, Lunn MPT, Notermans NC; IMAGiNe Study Group. 230th ENMC International Workshop: Improving future assessment and research in IgM anti-MAG peripheral neuropathy: A consensus collaborative effort, Naarden, The Netherlands, 24-26 February 2017. Neuromuscul Disord. 2017 Nov;27(11):1065-1072.28927829
7. Svahn J, Petiot P, Antoine JC, et al. Anti-MAG antibodies in 202 patients: clinicopathological and therapeutic features. J Neurol Neurosurg Psychiatry. 2018 May;89(5):499-505.29070644
8. Magy L, Kabore R, Mathis S, et al. Heterogeneity of Polyneuropathy Associated with Anti-MAG Antibodies. J Immunol Res. 2015;2015:450391.26065001
9. Dalakas MC. Rituximab in anti-MAG neuropathy: More evidence for efficacy and more predictive factors. J Neurol Sci. 2017 Jun 15;377:224-226.28477700
10. Joint Task Force of the EFNS and the PNS. European Federation of Neurological Societies/Peripheral Nerve Society Guideline on management of paraproteinemic demyelinating neuropathies. Report of a Joint Task Force of the European Federation of Neurological Societies and the Peripheral Nerve Society--first revision. J Peripher Nerv Syst. 2010 Sep;15(3):185-195.21040140
11. Vallat JM, Magy L, Ciron J, Corcia P, Le Masson G, Mathis S. Therapeutic options and management of polyneuropathy associated with anti-MAG antibodies. Expert Rev Neurother. 2016 Sep;16(9):1111-1119.27267749
12. Lunn MP, Nobile-Orazio E. Immunotherapy for IgM anti- myelin-associated glycoprotein paraproteinassociated peripheral neuropathies. Cochrane Database Syst Rev. 2016 Oct 4;10:CD002827.27701752
13. Emilien D, Hugh W. Diagnostic Utility of Auto Antibodies in Inflammatory Nerve Disorders. J Neuromuscul Dis. 2015 Jun 4;2(2):107-112.27858733
14. Latov N. Diagnosis and treatment of chronic acquired demyelinating polyneuropathies. Nat Rev Neurol. 2014 Aug; 10(8):435-446.24980070
15. Baron M, Lozeron P, Harel S, et al. Plasma exchanges for severe acute neurological deterioration in patients with IgM anti-myelin-associated glycoprotein (anti-MAG) neuropathy. J Neurol. 2017 Jun;264(6):1132-1135.28484839
16. Campagnolo M, Zambello R, Nobile-Orazio E, et al. IgM MGUS and Waldenstrom-associated anti-MAG neuropathies display similar response to rituximab therapy. J Neurol Neurosurg Psychiatry. Epub 2017 May 13.28501820
17. Gazzola S, Delmont E, Franques J, et al. Predictive factors of efficacy of rituximab in patients with anti-MAG neuropathy. J Neurol Sci. 2017 Jun 15;377:144-148.28477685
18. Léger JM, Viala K, Nicolas G, et al. Placebo-controlled controlled trial of rituximab in IgM anti-myelin-associated glycoprotein neuropathy. Neurology. 2013 Jun 11;80(24):2217-2225.23667063
19. Maurer MA, Rakocevic G, Leung CS, et al. Rituximab induces sustained reduction of pathogenic B cells in patients with peripheral nervous system autoimmunity. J Clin Invest. 2012 Apr;122(4):1393-1402.22426210
20. Gruson B, Ghomari K, Beaumont M, et al. Long-term response to rituximab and fludarabine combination in IgM anti-myelin-associated glycoprotein neuropathy. Peripher Nerv Syst. 2011 Sep;16(3):180-185.22003932
21. Sala E, Robert-Varvat F, Paul S, Camdessanche JP, Antione JC. Acute neurological worsening after Ritiximab treatment in patients with anti-MAG neuropathy. J Neurol Sci. 2014 Oct 15;345(1-2):224-227.25115501
22. Stork AC, Notermans NC, Vrancken AF, Cornblath DR, van der Pol WL. Rapid worsening of IgM anti-MAG demyelinating polyneuropathy during rituximab treatment. J Peripher Nerv Syst. 2013 Jun;18(2):189-191.23781968
23. Kuijf ML, Eurelings M, Tio-Gillen AP, et al. Detection of anti-MAG antibodies in polyneuropathy associated with IgM monoclonal gammopathy. Neurology. 2009 Sep 1;73(9):688-695.19720975
24. Jaskowski TD, Prince HE, Greer RW, Litwin CM, Hill HR. Further comparisons of assays for detecting MAG IgM autoantibodies. J Neuroimmunol. 2007 Jul;187(1-2):175-178.17537521
25. Caudie C, Kaygisiz F, Jaquet P, et al. Diagnostic value of autoantibodies to MAG by ELISA Buhlmann in 117 immune-mediated peripheral neuropathies associated with monoclonal IgM to SGPG/SGLPG. Ann Biol Clin (Paris). 2006 Jul-Aug;64(4):353-359.16829480

References

Dalakas MC. Pathogenesis of immune-mediated neuropathies. Biochim Biophys Acta. 2015 Apr;1852(4):658-666.24949885

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