Sulfated glucuronyl glycolipids reacting with anti-myelin-associated glycoprotein monoclonal antibodies including IgM paraproteins in neuropathy: species distribution and partial characterization of epitopes |
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| Authors: | A A Ilyas M C Dalakas R O Brady R H Quarles |
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| Affiliation: | 1. Division of Neurotoxicology, National Center for Toxicological Research, Food and Drug Administration, Jefferson, AR 72079, United States;2. Pediatric and Maternal Health Staff, Office of New Drugs, Center for Drug Evaluation Research, Food and Drug Administration, Silver Spring, MD 20993, United States;3. Division of Epidemiology II, Office of Pharmacovigilance and Epidemiology, Office of Surveillance and Epidemiology, Center for Drug Evaluation Research, Food and Drug Administration, Silver Spring, MD 20993, United States;1. Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10461, United States;2. Department of Medicine, Division of Endocrinology, Albert Einstein College of Medicine, Bronx, NY 10461, United States;3. Department of Obstetrics and Gynecology and Women''s Health, Albert Einstein College of Medicine, Bronx, NY 10461, United States;4. Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, United States;1. Division of General Surgery, Department of Surgery, Yung Kung Campus, Chi-Mei Medical Center, Tainan, Taiwan;2. Chia Nan University of Pharmacy & Science, Tainan, Taiwan;3. Department of Physiology & Biophysics, National Defense Medical Center (NDMC), Taipei, Taiwan;4. Department of Family and Community Health, Tri-Service General Hospital, NDMC, Taipei, Taiwan;5. Department of Medical Research, Tri-Service General Hospital, Taipei, Taiwan;1. Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, China;2. Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou 215163, China |
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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.(ABSTRACT TRUNCATED AT 250 WORDS) |
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