Demyeliating neuropathy and monoclonal IgM antibody to myelin‐associated glycoprotein

Steck, Andreas; Murray, Norman; Meier, Claus; Page, Nicole; Perruisseau, Geneviève

doi:10.1212/wnl.33.1.19

Cited by 205 publications

(81 citation statements)

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“…MAG may prove to be a useful marker for human NK cells. At present there is no evidence that the anti-MAG antibody in patients with IgM monoclonal gammopathy with demyelinating neuropathy (4,17) or the MAG positive cells in our present study play an important role in the pathogenesis of central and peripheral demyelinating autoimmune disorders. However, MAG positive cells may participate in the pathogenesis of such autoimmune disorders because NK cells play an important role not only as cytotoxic cells in tumorbearing or virus-infected individuals but also as suppressor cells in immunoregulation (2, 5).…”

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confidence: 72%

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Myelin-associated glycoprotein (MAG): Expression on the surface of human natural killer cells

Tanaka¹,

Sato²,

Yanagisawa³

et al. 1984

Biomed. Res.

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The characterization of mononuclear cells in human peripheral blood stained by anti-myelin-associated glycoprotein (MAG) antiserum was examined in a two-color immunofluorescence study and by rosetting with K-562 cells, the target cells of human natural killer cells. Human mononuclear cells consisting of more than 95% of MAG positive cells were also stained with Leu 7, a monoclonal antibody against human natural killer cells, but only 50 to 90 % of Leu 7 positive cells were stained with anti-MAG antiserum. The cells that expressed T cell antigen or monocyte antigen were also stained with anti-MAG antiserum Myelin-associated glycoprotein (MAG), with an apparent molecular weight of 105 kDa (16), is a quantitatively minor constituent of purified myelin (11), which is lost early in the development of multiple sclerosis plaques (6), and was recently reported to be the antigen for a monoclonal IgM in demyelinating neuropathy (4, 17).Recently, using enzyme-linked immunosorbent assay (15) and immunohistochemistry (unpublished data), we found that Leu 7 (HNK-1), a monoclonal antibody which identifies human natural killer (NK) cells, could label human MAG purified from myelin of the central and peripheral nervous system. We also found that the same antigenic determinant as MAG exists on the cell surface of mononuclear cells in human peripheral blood and that MAG positive cells of healthy individuals stained by a heterologous antiserum were 9.1;|;2.1% of mononuclear cells in human peripheral blood (18).In the present report, we demonstrate that MAG positive cells are closely related to Leu 7 positive cells and that NK cells conjugated to K-562 cells are stained by Leu 7 and also by anti-MAG antiserum.Myelin was prepared from white matter dissected from a human brain by the method of Norton and Poduslo (10), and MAG was isolated from the purified myelin by the lithium diiodosalicylate-phenol method (12). Prior to immunization, MAG was further purified by gel filtration on a Sepharose CL-6B column equilibrated with 0.5% (w/v) sodium dodecyl sulfate, 1mM dithiothreitol and 10mM Tris-HC1 (pH 7.4), and then dialyzed against deionized water (3). MAG (250 pg) was emulsified with complete Freund's adjuvant and injected into the back of a Japanese white rabbit. Boosters were given 3 and 5 weeks after the initial injection. The rabbit was bled 5 weeks after the last immunization. Anti-MAG antiserum did not react to erythrocyte ghosts, liver homogenate, or IgG Fc receptors of human mononuclear cells in the peripheral blood (18).

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confidence: 72%

“…Myelin-associated glycoprotein (MAG), with an apparent molecular weight of 105 kDa (16), is a quantitatively minor constituent of purified myelin (11), which is lost early in the development of multiple sclerosis plaques (6), and was recently reported to be the antigen for a monoclonal IgM in demyelinating neuropathy (4,17).…”

mentioning

confidence: 99%

Myelin-associated glycoprotein (MAG): Expression on the surface of human natural killer cells

Tanaka¹,

Sato²,

Yanagisawa³

et al. 1984

Biomed. Res.

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“…Expression of the HNK-1 structure is spatially and temporally regulated, suggesting an important role in axon outgrowth (33). It is a predominant autoantigen in demyelinating diseases of the peripheral nervous system (34). Recently this glycan has been recognized to be a crucial player in synaptic plasticity involving inhibitory interneurons in the hippocampus (35).…”

Section: May Fulfill a Number Of Different Roles In Vivomentioning

confidence: 99%

Molecular Cloning and Expression of the Pituitary Glycoprotein HormoneN-Acetylgalactosamine-4-O-sulfotransferase

Xia¹,

Evers²,

Kang³

et al. 2000

Journal of Biological Chemistry

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The pituitary hormones LH, 1 thyrotropin, and pro-opiomelanocortin bear unique N-linked oligosaccharides that terminate with the sequence SO 4 -4-GalNAc␤1,4GlcNAc␤1,2Man␣ (1-6).The terminal GalNAc-4-SO 4 is recognized by a receptor, the Man/GalNAc-4-SO 4 receptor (7-9), which is located in hepatic endothelial cells and controls the circulatory half-life of LH and other glycoproteins bearing this structure (10, 11). A short circulatory half-life in conjunction with the regulated release from storage granules in the gonadotroph produces the episodic rise and fall seen in circulating LH levels (12, 13). This is essential for efficient activation of the LH receptor in the ovary and testis due to the down-regulation and internalization of the activated receptor by ␤-arrestin (14). Sequential actions of a hormone-specific ␤1,4 GalNAc-transferase and a GalNAc-4-sulfotransferase are required for the synthesis of GalNAc-4-SO 4 on LH and other glycoproteins (13,(15)(16)(17)(18)(19). Three key functions have been conserved throughout vertebrate evolution: 1) the peptide recognition determinant utilized by the GalNAc-transferase, 2) the GalNAc-transferase itself, and 3) the GalNAc-4-sulfotransferase. As a result, Nlinked structures terminating with ␤1,4-linked GalNAc-4-SO 4 occur on glycoprotein hormones from all vertebrate species (20). GalNAc-transferase and GalNAc-4-sulfotransferase activities with the same properties as those expressed in the pituitary have been detected in other tissues and cells (21). Furthermore, a number of other glycoproteins bearing N-and O-linked structures terminating with ␤1,4-linked GalNAc-4-SO 4 have been described (2,5,(22)(23)(24)(25)(26). Thus, oligosaccharides terminating with GalNAc-4-SO 4 may fulfill a number of different roles in vivo.Recently the HNK-1 sulfotransferase (HNK-1 ST), a glucuronyl-3-sulfotransferase that mediates synthesis of the HNK-1 epitope SO 4 -3-GlcA␤1,3Gal␤1,4GlcNAc (27) was cloned (28, 29). The HNK-1 structure is found in the central and peripheral nervous systems on glycolipids and glycoproteins involved in neural recognition and synaptogenesis (Ref. 30; for reviews, see Refs. 31 and 32). Expression of the HNK-1 structure is spatially and temporally regulated, suggesting an important role in axon outgrowth (33). It is a predominant autoantigen in demyelinating diseases of the peripheral nervous system (34). Recently this glycan has been recognized to be a crucial player in synaptic plasticity involving inhibitory interneurons in the hippocampus (35). The sulfate group of the HNK-1 glycan is essential for its function (36, 37).

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“…Although the etiology of this type of neuropathy remains unknown, the deposition of antibodies on the myelin sheaths of nerves (2)(3)(4)(5)(6)(7)(8) and the binding of IgM and IgG paraproteins to peripheral nerve myelin (6)(7)(8)(9)(10)(11)(12) suggest that the paraproteins play a causative role in neuropathy. Moreover, IgM paraproteins from some polyneuropathy patients have been found to react with human myelin-associated glycoprotein (MAG) by several groups (13)(14)(15)(16). Recently, these antibodies have been shown to react with the carbohydrate moeities of MAG (16)(17)(18), acidic glycolipids of human peripheral nerve (16,19), and low Mr glycoproteins in the peripheral nervous system (18,20,21).…”

Section: Introductionmentioning

confidence: 99%

Polyneuropathy with monoclonal gammopathy: glycolipids are frequently antigens for IgM paraproteins.

Ilyas¹,

Quarles

Dalakas

et al. 1985

Proc. Natl. Acad. Sci. U.S.A.

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Immunoglobulins from patients with paraproteinemic polyneuropathy were screened for reactivity with nerve and brain glycolipids by ELISA and/or a thin-layerchromatogram-overlay technique. The myelin-associated glycoprotein (MAG) has been shown to be an antigen in many neuropathy patients with IgM gammopathy, but this study focused on seven neuropathy patients in which the IgM paraproteins had been shown not to react with this glycoprotein. Five of these seven had IgM that reacted with components in the acidic glycolipid fraction of human sciatic nerve, and three of these IgMs also reacted with components in the acidic glycolipid fraction of human brain. Little or no reactivity with glycolipids was detected for two patients with neuropathy and IgG gammopathy or for two with neuropathy and IgA gammopathy. The results suggest that neuropathy-patient IgM paraproteins not reactive with MAG often react with acidic glycolipids and thus define a subset of paraproteinemic neuropathies. Since the IgM paraproteins that react with MAG also react with acidic glycolipids of nerve, glycolipid antigens appear to be quite common among the IgM paraproteinemic neuropathies.

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Demyeliating neuropathy and monoclonal IgM antibody to myelin‐associated glycoprotein

Cited by 205 publications

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<b>Myelin-associated glycoprotein (MAG): Expression on the surface of human natural killer </b><b>cells </b>

<b>Myelin-associated glycoprotein (MAG): Expression on the surface of human natural killer </b><b>cells </b>

Molecular Cloning and Expression of the Pituitary Glycoprotein HormoneN-Acetylgalactosamine-4-O-sulfotransferase

Polyneuropathy with monoclonal gammopathy: glycolipids are frequently antigens for IgM paraproteins.

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