Anti-MAG (IgM)

Optimal Result: 0.1 - 10 Units.

Myelin-associated glycoprotein (MAG) is a trans-membrane protein of both the central nervous system (CNS) and peripheral nervous system (PNS) myelin (= an insulating layer, or sheath that forms around nerves), involved in the process of myelination (= the formation of a myelin sheath).

Key Terms/Glossary:

Myelin-associated glycoprotein (MAG):

Myelin associated glycoprotein (MAG) is found in central and peripheral nervous system myelin. MAG appears on oligodendrocytes and Schwann cells. The localisation of MAG in the peripheral region in myelin suggests that MAG may participate in neuron-glial cell interaction that leads to myelination.

Central nervous sytstem:

The central nervous system (CNS) is made up of the brain and spinal cord. It is one of 2 parts of the nervous system. The other part is the peripheral nervous system.

Peripheral nervous system:

Your peripheral nervous system (PNS) is that part of your nervous system that lies outside your brain and spinal cord. It plays key role in both sending information from different areas of your body back to your brain, as well as carrying out commands from your brain to various parts of your body.

Peripheral neuropathy:

Peripheral neuropathy refers to the many conditions that involve damage to the peripheral nervous system, which is a vast communications network that sends signals between the central nervous system (the brain and spinal cord) and all other parts of the body.

Anti-MAG peripheral neuropathy is a very rare disease caused by anti-MAG antibodies that destroy MAG protein leading to disruptions of normal myelin production and healthy peripheral nerve activity.

In this type of Peripheral Neuropathy, a person’s own immune system attacks cells that are specific in maintaining a healthy peripheral nervous system. As these cells are destroyed by antibodies, they lose function and create problems in both sensory and motor function.

Anti-MAG neuropathy is often associated with “monoclonal gammopathy of undetermined significance (MGUS),” a potentially cancerous (but usually benign) condition characterized by a similar over production of serum immunoglobulins.

References:

Svahn J, Petiot P, Antoine J The Francophone anti-MAG cohort Group, et al Anti-MAG antibodies in 202 patients: clinicopathological and therapeutic features Journal of Neurology, Neurosurgery & Psychiatry 2018;89:499-505.

Quarles RH. Myelin-associated glycoprotein (MAG): past, present and beyond. J Neurochem. 2007 Mar;100(6):1431-48. doi: 10.1111/j.1471-4159.2006.04319.x. Epub 2007 Jan 4. PMID: 17241126.

Links:

https://medlineplus.gov/ency/article/002261.htm#:~:text=Myelin%20is%20an%20insulating%20layer,efficiently%20along%20the%20nerve%20cells.

https://www.kenhub.com/en/library/anatomy/the-myelin-sheath-and-myelination

https://www.foundationforpn.org/causes/anti-mag/

https://my.clevelandclinic.org/health/body/23123-peripheral-nervous-system-pns#:~:text=Your%20peripheral%20nervous%20system%20(PNS)%20is%20that%20part%20of%20your,various%20parts%20of%20your%20body.

https://www.ninds.nih.gov/health-information/disorders/peripheral-neuropathy#:~:text=Peripheral%20neuropathy%20refers%20to%20the,other%20parts%20of%20the%20body.

What does it mean if your Anti-MAG (IgM) result is too high?

Anti-MAG peripheral neuropathy is a very rare disease caused by anti-MAG antibodies that destroy MAG protein leading to disruptions of normal myelin production and healthy peripheral nerve activity.

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→ 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. 

→ 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. However, the clinical presentation of these patients can be variable, suggesting autoimmunity to other components of myelin may play a role in the disease.

→ 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. 

→ Anti-MAG IgM has also been identified in Waldenstrom's macroglobulinemia and IgM secreting lymphoma. These MAG autoantibodies are believed to be pathogenic. 

Patients with anti-MAG antibodies may respond favorably to therapeutic intervention but to date there is no consensus on the treatment of this disease. Testing for the presence of these autoantibodies is useful for diagnosis as well as for monitoring of therapy.

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.

Recent reports suggest Rituximab may be effective in some patients with anti-MAG neuropathy.

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