Serum anti‐GQ_1b IgG antibodies recognize surface epitopes on Campylobacter jejuni from patients with Miller Fisher syndrome

Abstract

Three patients who had diarrhea prior to the development of Miller Fisher syndrome are presented. Campylobacter jejuni was isolated from stool specimens from all patients. High titers of anti-GQ1b IgG antibodies were demonstrated in the serum of these patients by enzyme-linked immunosorbent assay and thin-layer chromatography overlay. In enzyme-linked immunosorbent assay inhibition studies the anti-GQ1b IgG antibodies bound specifically to whole bacteria of the Miller Fisher syndrome-associated C. jejuni strains. The presence of anti-GQ1b IgG binding epitopes on the surface of the C. jejuni from the patients was not exclusively associated with a specific Penner serotype. It is suggested that anti-GQ1b antibodies are formed during the initial infection that elicits Miller Fisher syndrome. The cross-reactivity of anti-GQ1b IgG antibodies with surface epitopes on Miller Fisher syndrome-associated C. jejuni strains supports the hypothesis of molecular mimicry between bacteria and neural tissue.

A somatically mutated human antiganglioside IgM antibody that induces experimental neuropathy in mice is encoded by the variable region heavy chain gene, V1-18.

“…MFS bears a strong clinical resemblance to the phenotype seen in the CANOMAD and over 95% of MFS cases have IgG antibodies to epitopes present on GQ1b and GT1a and other NeuAc(␣2-8)NeuAc(␣2-3)Gal configured gangliosides including GD1b, GT1b, and GD3 (53)(54)(55). It has previously been shown that both the anti-GQ1b antibodies in MFS sera and anti-GM1 antibodies in GBS sera react with carbohydrate epitopes on Cj LPS, and the model proposed for the illness is thus one of molecular mimicry in which the humoral immune response to Cj LPS fortuitously cross-reacts with neural ganglioside antigens, thereby inducing the neuropathy (7)(8)(9)(10)(11). It is possible that antidisialosyl IgM antibodies that occur in CAN-OMAD patients also arise as a result of an immune response primarily generated towards bacterial LPS, in the same way that IgM anti-GM1 antibodies from motor neuropathy patients have been shown to react with Cj LPS.…”

“…Several distinct phenotypes of autoimmune neuropathy are associated with high serum levels of antiganglioside antibodies (3)(4)(5)(6). Current evidence suggests that antiganglioside antibodies arise as a result of molecular mimicry with structurally similar bacterial lipopolysaccharides that provide the antigenic stimulation for their production (7)(8)(9)(10)(11). It is assumed that the antibodies induce neuropathy by binding to nerve surface gangliosides and activating proinflammatory pathways or by causing physiological block of ganglioside-modulated peripheral nerve functions.…”

Detection of Conserved N-Linked Glycans and Phase-variable Lipooligosaccharides and Capsules from Campylobacter Cells by Mass Spectrometry and High Resolution Magic Angle Spinning NMR Spectroscopy

“…jejuni LOSs have received much attention due to their unique mimicry of human ganglioside structures (21,22) and their potential involvement in the induction of the autoimmune polyneuropathies, Guillain-Barré (GBS), and Miller Fisher syndromes (23,24). C. jejuni LOSs have also recently been shown to be phase-variable and important in virulence (25)(26)(27).…”

The current place of high-dose immunoglobulins in the treatment of neuromuscular disorders

“…In Miller-Fisher syndrome similarly anti-GQ1b antibodies could only be absorbed using C. jejuni bacteria isolated from the patients themselves. 48,49 Finally, a pathophysiological effect of IgG containing anti-GQ1b antibodies of Miller-Fisher patients has been demonstrated in a mouse phrenic nerve/diaphragm preparation. 68 All these findings lead to the hypothesis that an infectious agent induces in susceptible persons an immune response involving antibodies cross-reacting with gangliosides present in peripheral nerves.…”

“…1). 48 The relation between C. jejuni infection and the occurrence of antiganglioside antibodies has also been more directly studied. C. jejuni isolated from GBS patients contain a GM1-like structure.…”