Anti-peripheral nerve myelin antibodies in Guillain-Barre syndrome bind a neutral glycolipid of peripheral myelin and cross-react with Forssman antigen.

Abstract

During acute-phase illness, serum of patients with GuillainBarre 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 (CFIT) 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 CiFF 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/mi). 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.

Terminal complement complexes concomitantly stimulate proliferation and rescue of Schwann cells from apoptosis

“…The sensitizing antibody used in all studies was a complement-fixing, antiperipheral nerve myelin immunoglobulin M (IgM) antibody from acute-phase GBS patient plasma and has been described previously by Koski et al (1986), and it was purified by ammonium sulfate/polyethelene glycol precipitation (Tatum, 1993). This antibody was characterized previously for its ability to facilitate complement-dependent demyelination of dissociated dorsal root ganglion/Schwann cell cocultures (Sawant-Mané et al, 1991, 1994 as well as its ability to bind myelin-associated glycolipids and mediate cytolysis of rodent Schwann cells (Koski et al, 1989;Sawant-Mané et al, 1994, 1996. After expansion with D-10 with BPE and forskolin, Schwann cells were incubated with excess antibody for 30 min at room temperature then stimulated with a complement source.…”

Guillain-Barr� syndrome and chronic inflammatory demyelinating polyneuropathy: Immune mechanisms and update on current therapies

“…The gangliosides GM, and GDIb, for instance, share the epitope Gal@ 1-3)GalNAc and therefore serum may contain antibodies with this fine specificity that cross-react between these two gangliosides. Antibodies against GM, are, however, not spe-\ Sl6 Annals of Neurology Supplement 1 to Volume 37,1995 cific for GBS, as they are also found in other disorders, especially lower motor neuron disease and multifocal motor neuropathy [58,591. In some studies in GBS patients, the presence of anti-GM, antibodies tended to be related to a more severe clinical course [SO, 60,611, but others did not support this 146,481.…”

Guillain-Barré Syndrome and Related Disorders

“…Furthermore, the observed clinical recovery following removal or neutralization of autoantibodies (or other pathogenic humoral factors) by plasmapheresis or intravenous immune globulin (IVIG) supports a role for B-cell-mediated processes in the pathogenesis of GBS [ 44 ] . Koski et al demonstrated that elevated serum levels of complement-fi xing anti-myelin antibodies correlated with disease activity in patients with GBS [ 45,46 ] . Recent autopsy studies revealed that local complement activation occurs at the site of nerve lesion, such as the axolemma in patients with AMAN and the Schwann cell membrane in patients with AIDP [ 47,48 ] .…”