2009•NeurologyRequires access

Detection of anti-MAG antibodies in polyneuropathy associated with IgM monoclonal gammopathy

Mark L. Kuijf, Marijke Eurelings, Anne P. Tio‐Gillen, Pieter A. van Doorn, Leonard H. van den Berg, Herbert Hooijkaas, J. Stork, Nicolette C. Notermans, Bart C. Jacobs

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Abstract

BACKGROUND: Detection of serum antibodies to myelin-associated glycoprotein (MAG) by Western blot (WB) is a valuable assay to diagnose a distinct type of demyelinating polyneuropathy with immunoglobulin M (IgM) monoclonal gammopathy. In this study, the diagnostic accuracy of a new and more practical ELISA to detect these antibodies was validated. METHODS: Routine WBs from 2 independent laboratories and ELISA were used to detect anti-MAG IgM in serum from 207 patients with neuropathy and controls. The sensitivity and specificity of these assays were compared and related to the patient clinical and electrophysiologic characteristics. RESULTS: In ELISA, anti-MAG antibodies were found in serum from 49 (72%) of 68 patients with demyelinating polyneuropathy and IgM monoclonal gammopathy. However, in this subgroup of patients, only 30 (44%) and 37 (54%) were positive in the 2 WBs. All of the patients positive in the 2 WBs were also positive in ELISA. A high correlation was found for IgM activity in ELISA to MAG and sulfate-3-glucuronyl paragloboside (SGPG) (Spearman rho = 0.72, p < 0.0001), supporting the notion that the shared sulfated glucuronic acid moiety of MAG and SGPG is preserved. Most patients positive in anti-MAG ELISA had a slowly progressive sensory-motor demyelinating polyneuropathy, even if the WB was negative. In control groups, however, 4 WB-negative patients with a nondemyelinating monoclonal gammopathy-related polyneuropathy were positive in anti-MAG ELISA. The remaining samples were negative in ELISA. CONCLUSION: ELISA is more sensitive than Western blot to diagnose anti-myelin-associated glycoprotein related polyneuropathy, although a positive serology may be found in other forms of polyneuropathy as well.

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BACKGROUND: Detection of serum antibodies to myelin-associated glycoprotein (MAG) by Western blot (WB) is a valuable assay to diagnose a distinct type of demyelinating polyneuropathy with immunoglobulin M (IgM) monoclonal gammopathy. In this study, the diagnostic accuracy of a new and more practical ELISA to detect these antibodies was validated. METHODS: Routine WBs from 2 independent laboratories and ELISA were used to detect anti-MAG IgM in serum from 207 patients with neuropathy and controls. The sensitivity and specificity of these assays were compared and related to the patient clinical and electrophysiologic characteristics. RESULTS: In ELISA, anti-MAG antibodies were found in serum from 49 (72%) of 68 patients with demyelinating polyneuropathy and IgM monoclonal gammopathy. However, in this subgroup of patients, only 30 (44%) and 37 (54%) were positive in the 2 WBs. All of the patients positive in the 2 WBs were also positive in ELISA. A high correlation was found for IgM activity in ELISA to MAG and sulfate-3-glucuronyl paragloboside (SGPG) (Spearman rho = 0.72, p < 0.0001), supporting the notion that the shared sulfated glucuronic acid moiety of MAG and SGPG is preserved. Most patients positive in anti-MAG ELISA had a slowly progressive sensory-motor demyelinating polyneuropathy, even if the WB was negative. In control groups, however, 4 WB-negative patients with a nondemyelinating monoclonal gammopathy-related polyneuropathy were positive in anti-MAG ELISA. The remaining samples were negative in ELISA. CONCLUSION: ELISA is more sensitive than Western blot to diagnose anti-myelin-associated glycoprotein related polyneuropathy, although a positive serology may be found in other forms of polyneuropathy as well.

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Available abstract

BACKGROUND: Detection of serum antibodies to myelin-associated glycoprotein (MAG) by Western blot (WB) is a valuable assay to diagnose a distinct type of demyelinating polyneuropathy with immunoglobulin M (IgM) monoclonal gammopathy. In this study, the diagnostic accuracy of a new and more practical ELISA to detect these antibodies was validated. METHODS: Routine WBs from 2 independent laboratories and ELISA were used to detect anti-MAG IgM in serum from 207 patients with neuropathy and controls. The sensitivity and specificity of these assays were compared and related to the patient clinical and electrophysiologic characteristics. RESULTS: In ELISA, anti-MAG antibodies were found in serum from 49 (72%) of 68 patients with demyelinating polyneuropathy and IgM monoclonal gammopathy. However, in this subgroup of patients, only 30 (44%) and 37 (54%) were positive in the 2 WBs. All of the patients positive in the 2 WBs were also positive in ELISA. A high correlation was found for IgM activity in ELISA to MAG and sulfate-3-glucuronyl paragloboside (SGPG) (Spearman rho = 0.72, p < 0.0001), supporting the notion that the shared sulfated glucuronic acid moiety of MAG and SGPG is preserved. Most patients positive in anti-MAG ELISA had a slowly progressive sensory-motor demyelinating polyneuropathy, even if the WB was negative. In control groups, however, 4 WB-negative patients with a nondemyelinating monoclonal gammopathy-related polyneuropathy were positive in anti-MAG ELISA. The remaining samples were negative in ELISA. CONCLUSION: ELISA is more sensitive than Western blot to diagnose anti-myelin-associated glycoprotein related polyneuropathy, although a positive serology may be found in other forms of polyneuropathy as well.

Key concepts: Polyneuropathy, Gammopathy, Antibody, Medicine, Serology, Myelin-associated glycoprotein, Chronic inflammatory demyelinating polyneuropathy, Immunology

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