Anti-peripheral nerve myelin antibodies in Guillain-Barre syndrome bind a neutral glycolipid of peripheral myelin and cross-react with Forssman antigen.
During acute-phase illness, serum of patients with Guillain-Barre syndrome (GBS) contain complement-fixing antibodies (Ab) to peripheral nerve myelin (PNM). We investigated PNM lipids as putative antigens for these Ab since GBS serum retained significant reactivity to PNM treated with protease. Ab binding to specific lipids was studied with a C1 fixation and transfer (C1FT) assay using fractions of PNM lipid reincorporated into liposomes as antigen targets or to lipids on HPTLC plates with peroxidase-labeled goat Ab to human IgM. Reactivity was detected to a neutral glycolipid (NGL) of human PNM with a similar number of carbohydrates residues to that of Forssman hapten (Forss). Anti-NGL Ab titers in GBS patients (50-220 U/ml) were significantly elevated over disease and normal controls (0-5 and 0-6 U/ml). We studied possible antigenic cross-reactivity of these Ab with Forss by first quantitating Ab activity with C1FT assay and liposomes containing Forss. All 12 GBS sera tested showed titers (54-272 U/ml) significantly elevated over 11 disease controls (0-22 U/ml) and 25 normal controls (0-11 U/ml). GBS serum Ab reacted with Forss isolated from dog nerve or sheep erythrocytes on HPTLC plates. Further, absorption of 80-100% of anti-NGL Ab activity and 17-97% of anti-PNM Ab activity from eight GBS patient serums was accomplished with liposomes containing Forss but not with control liposomes. In seven GBS patients anti-NGL Ab activity represented only a portion of anti-PNM Ab activity. These results suggest that a glycolipid with antigenic cross-reactivity to Forssman hapten may be responsible for some of the anti-PNM Ab activity in GBS.
Koski
C L
CL
Department of Neurology, University of Maryland School of Medicine, Baltimore 21201.
Chou
D K
DK
Jungalwala
F B
FB
D000906:Antibodies / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology; D002855:Chromatography, Thin Layer; D003172:Complement C1 / Q000276:immunology; D003429:Cross Reactions; D005577:Forssman Antigen / Q000276:immunology; D006017:Glycolipids / Q000378:metabolism*; D006801:Humans; D007075:Immunoglobulin M / Q000378:metabolism; D009186:Myelin Sheath / Q000276:immunology* / Q000378:metabolism; D010525:Peripheral Nerves / Q000276:immunology*; D011129:Polyradiculoneuropathy / Q000276:immunology*; D011402:Pronase / Q000494:pharmacology
D000906:Antibodies; D000911:Antibodies, Monoclonal; D003172:Complement C1; D006017:Glycolipids; D007075:Immunoglobulin M; D005577:Forssman Antigen; D011402:Pronase