Characterization of sulfated glucuronic acid containing glycolipids reacting with IgM M-proteins in patients with neuropathy.

T Ariga,T Kohriyama,L Freddo,N Latov,M Saito,K Kon,S Ando,M Suzuki,M E Hemling,K L Rinehart

doi:10.1016/s0021-9258(19)75864-5

Abstract

In some patients with neuropathy and plasma cell dyscrasia, the serum IgM M-proteins are known to bind to the myelin associated glycoprotein and to peripheral nerve glycolipids. We have isolated two acidic glycolipids which bind to the M-protein from human cauda equina by DEAE-Sephadex, Iatrobeads, and high performance liquid column chromatographies. The major acidic glycolipid migrated between GM1 and GD1a and the minor acidic glycolipid migrated between GD1a and GD1b. Their structures were elucidated by sugar analysis, enzymatic digestion, mild acid hydrolysis, permethylation, fast atom bombardment mass spectrometry, and NMR studies. Their core structure was confirmed to be paragloboside by high performance thin-layer chromatography-immunostaining using anti-paragloboside monoclonal antibody. Both acidic glycolipids lacked sialic acid but contained sulfated glucuronic acid as their acidic moiety. The sulfate group in the glucuronic acid was established by periodate oxidation and permethylation studies to be attached to the 3 position. The structures of the two acidic glycolipids are therefore consistent with the following: IV3GlcUA(3-sulfate)nLcOse4Cer and VI3GlcUA(3-sulfate)nLcOse6Cer. Additionally, the free carboxyl group on the glucuronic acid residue was shown to be necessary to bind the IgM M-proteins from neuropathy patients.

Highlights

In some patients with neuropathy and plasma cell somepatientswithneuropathy and plasmacelldyscrasia dyscrasia, the serum IgM“proteins are knownto thereareIgM“proteins that reactwithmyelin [5,6,7,8] or bind to the myelin associated glycoprotein and to pe- with myelin-associated glycoprotein (MAG)’
Recent studies have indicated that the “proteins bind glycolipids which bind to the “protein from human t o a carbohydrate determinant shared bay number of periphcaudaequina byDEAE-Sephadex,Iatrobeads,and eral nerve glycoproteins, including MAG, and by two acidic high performanceliquid columnchromatographies
GD1, and GDlh.Their structures were elucidated by sugar analysis, enzymatic digestionm, ild acid hydrolysis,permethylation,fastatombombardment mass spectrometry, and NMR studies

Summary

The major acidicglycolipid migrated between GMMI

GD1, and GDlh.Their structures were elucidated by sugar analysis, enzymatic digestionm, ild acid hydrolysis,permethylation,fastatombombardment mass spectrometry, and NMR studies. Their core structure agrneldypcoorltiepdidtsh ai ntp et hr iepr ehaecrtai lvneegrlvyec o l i p(i1d2sl-a1c5k).s i aWl i ceahcaivder e cen tly and are not gangliosideasnd that anti-MAG “proteins probably bind to the same or closelyrelatedcarbohydrate determinants of both the glycoproteins and glycolipids [15]. Chou et al [16]havetentativelycharacterizedthemajor was confirmed to be paragloboside by high perform- glycolipid(SGPG)antigen as sulfatedglucuronicacid-conance thin-layer chromatography-immunostaining us- taining paragloboside In this paperwe describe the isolationand characterization acidic glycolipids lacked sialic acid but contained sul- of both acidic glycolipidsS, GPG and SGLPG, from the human fated glucuronic aciads their acidicmoiety. Glycolipids are consistent with thfoellowing: IV3GlcUA(3-sulfate)nLcOselCer and V13GlcUA(3-sul-

DISCUSSION

Peripheral NervSoyusstem GlycolipidsfrHomuman Cauda Equina

SUPPLEUENTAL UATERIAL TO

Peripheral Nervous System Glycolipidsfrom Human Cauda Equina

Fatty acid