Sulfated glucuronyl glycolipids reacting with anti-myelin-associated glycoprotein monoclonal antibodies including IgM paraproteins in neuropathy

Species distribution and partial characterization of epitopes

Amjad Ilyas, Marinos C. Dalakas, Roscoe O. Brady, Richard H. Quarles

Research output: Contribution to journalArticle

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Abstract

It was recently established that anti-myelin associated glycoprotein (MAG) IgM paraproteins associated with neuropathy and a substantial number of experimentally produced rat and mouse monoclonal antibodies that react with MAG (e.g. HNK-1) also bind to some sulfated glucuronic acid-containing sphingoglycolipids of human peripheral nerve. A species study revealed that these glycolipids could be detected readily by TLC overlay experiments in the acidic glycolipid fractions from human, monkey, bovine, cat and dog peripheral nerve. The glycolipids were also present in the nerves of rat, mouse, rabbit, guinea pig and chicken, but their concentration was about an order of magnitude lower. These antigenic glycolipids were present in the purified myelin fraction from cat nerve, but their level was not enriched over that in whole homogenate. Partial characterization of the epitopes in the glycolipids was accomplished by comparing binding of the human and experimental monoclonal antibodies to sulfated glucuronyl paragloboside (SGPG), to the desulfated lipid (GPG), and to the methyl ester of the desulfated lipid (MeGPG). All of the human, mouse and rat antibodies reacted with the intact SGPG, but none exhibited binding to MeGPG indicating that either the sulfate or the free carboxyl group on SGPG was required for reactivity. Five out of 11 human IgM paraproteins retained partial and variable reactivity with GPG showing that the sulfate was not absolutely required for binding, while the other 6 did not react with GPG. These results demonstrate idiotypic heterogeneity among the IgM paraproteins. Only 1 of 14 monoclonal antibodies produced experimentally in mice or rats retained reactivity with GPG. The data indicate that the sulfated glucuronic acid moiety of the glycolipid is a critical part of the antigenic determinant for all of the human, mouse and rat monoclonal antibodies tested.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalBrain research
Volume385
Issue number1
DOIs
StatePublished - Oct 15 1986
Externally publishedYes

Fingerprint

Myelin-Associated Glycoprotein
Paraproteins
Glycolipids
Immunoglobulin M
Epitopes
Monoclonal Antibodies
Glucuronic Acid
Peripheral Nerves
Sulfates
Cats
Lipids
Glycosphingolipids
Myelin Sheath
Haplorhini
sulfoglycolipids
Chickens
Guinea Pigs
Esters
Dogs
Rabbits

All Science Journal Classification (ASJC) codes

  • Clinical Neurology
  • Molecular Biology
  • Neuroscience(all)
  • Developmental Biology

Cite this

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title = "Sulfated glucuronyl glycolipids reacting with anti-myelin-associated glycoprotein monoclonal antibodies including IgM paraproteins in neuropathy: Species distribution and partial characterization of epitopes",
abstract = "It was recently established that anti-myelin associated glycoprotein (MAG) IgM paraproteins associated with neuropathy and a substantial number of experimentally produced rat and mouse monoclonal antibodies that react with MAG (e.g. HNK-1) also bind to some sulfated glucuronic acid-containing sphingoglycolipids of human peripheral nerve. A species study revealed that these glycolipids could be detected readily by TLC overlay experiments in the acidic glycolipid fractions from human, monkey, bovine, cat and dog peripheral nerve. The glycolipids were also present in the nerves of rat, mouse, rabbit, guinea pig and chicken, but their concentration was about an order of magnitude lower. These antigenic glycolipids were present in the purified myelin fraction from cat nerve, but their level was not enriched over that in whole homogenate. Partial characterization of the epitopes in the glycolipids was accomplished by comparing binding of the human and experimental monoclonal antibodies to sulfated glucuronyl paragloboside (SGPG), to the desulfated lipid (GPG), and to the methyl ester of the desulfated lipid (MeGPG). All of the human, mouse and rat antibodies reacted with the intact SGPG, but none exhibited binding to MeGPG indicating that either the sulfate or the free carboxyl group on SGPG was required for reactivity. Five out of 11 human IgM paraproteins retained partial and variable reactivity with GPG showing that the sulfate was not absolutely required for binding, while the other 6 did not react with GPG. These results demonstrate idiotypic heterogeneity among the IgM paraproteins. Only 1 of 14 monoclonal antibodies produced experimentally in mice or rats retained reactivity with GPG. The data indicate that the sulfated glucuronic acid moiety of the glycolipid is a critical part of the antigenic determinant for all of the human, mouse and rat monoclonal antibodies tested.",
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Sulfated glucuronyl glycolipids reacting with anti-myelin-associated glycoprotein monoclonal antibodies including IgM paraproteins in neuropathy : Species distribution and partial characterization of epitopes. / Ilyas, Amjad; Dalakas, Marinos C.; Brady, Roscoe O.; Quarles, Richard H.

In: Brain research, Vol. 385, No. 1, 15.10.1986, p. 1-9.

Research output: Contribution to journalArticle

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