title: Sensory neuropathy with monoclonal IgM binding to a trisulfated heparin disaccharide.
abstract: We studied clinical and serological features of five patients with polyneuropathy and serum immunoglobulin M (IgM) binding to the trisulfated disaccharide IdoA2S-GlcNS-6S (TS-HDS), the most abundant disaccharide component of heparin oligosaccharides. The patients all had painful, predominantly sensory polyneuropathies. Sensory loss was distal and panmodal. Electrophysiological and pathological studies were consistent with axonal loss, especially of unmyelinated axons. Immunohistochemistry showed IgM and kappa light chains deposited around the rim of intermediate-sized veins in the perimysium and epineurium. Serum IgM binding to TS-HDS was selective, present in high titer (>12,000), and limited to kappa light chains. We conclude that TS-HDS is a newly identified target carbohydrate antigen of some IgM M-proteins. Monoclonal IgM binding to TS-HDS is associated with a painful, predominantly sensory, polyneuropathy syndrome with axonal loss and deposition of IgM in veins. The role of IgM binding to TS-HDS in the pathogenesis of the neuropathy remains to be determined.
authors.affiliation: Washington University School of Medicine, Department of Neurology, Box 8111, 660 South Euclid Ave., St. Louis, MO 63110, USA. pestronk@kids.wustl.edu
authors.forename: Alan
authors.initials: A
authors.lastname: Pestronk
authors.forename: Rati
authors.initials: R
authors.lastname: Choksi
authors.forename: Eric
authors.initials: E
authors.lastname: Logigian
authors.forename: Muhammad T
authors.initials: MT
authors.lastname: Al-Lozi
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000097:blood* / Q000276:immunology; D001706:Biopsy; D004187:Disaccharides / Q000737:chemistry / Q000276:immunology*; D005260:Female; D006493:Heparin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000294:innervation / Q000473:pathology; D036421:Nerve Fibers, Unmyelinated / Q000473:pathology; D009431:Neural Conduction; D009475:Neurons, Afferent / Q000276:immunology*; D011115:Polyneuropathies / Q000276:immunology* / Q000473:pathology; D011485:Protein Binding / Q000276:immunology; D013431:Sulfates / Q000737:chemistry / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D004187:Disaccharides; D007075:Immunoglobulin M; D013431:Sulfates; C464536:heparin disaccharide; D006493:Heparin