Monoclonal antibodies raised against Guillain-Barré syndrome–associated Campylobacter jejuni lipopolysaccharides react with neuronal gangliosides and paralyze muscle-nerve preparations

Abstract

Ganglioside binding properties were calculated from half-maximal binding studies and graded as follows: 0,-; <10 2 , +; >10 2 <10 3 , ++; >10 3 , +++. LPS reactivity as assessed by ELISA and TLC overlay is scored as present (+) or absent (-). See Methods.

Identification of two aberrant transcripts derived from a hybridoma with amplification of functional immunoglobulin variable genes

“…This unexpected abVH-LF8 showed high homology to both aberrant genes and functional ones, according to the GenBank database. The results confirm the homology of P3-X63-Ag8.653 and OUR-1, an ouabain-resistant subclone of the former, 29 and verify that some aberrant V H genes have high homology to the functional ones. It could be confusing to distinguish functional V H genes from aberrant ones.…”

Ganglioside Molecular Mimicry and Its Pathological Roles in Guillain-Barré Syndrome and Related Diseases

“…More than 90% of patients with Miller-Fisher syndrome have sera with anti-GQ1b and anti-GT1a antibodies, which may also react with other disialylated gangliosides, including GD3 and GD1b. Structural studies on LPSs from neuropathy-associated C. jejuni strains have revealed GT1a-like and GD3-like core oligosaccharides (27). The LPS cores of a C. jejuni strain of serotype HS:10 isolated from a patient with Miller-Fisher syn- drome have a terminal trisaccharide epitope of GD3 ganglioside (67).…”

“…This trisaccharide epitope is also present in LPS cores of serotype HS:19 strains from patients with GBS (67). Goodyear et al (27) reported that the OH4382 isolate (HS:19 serotype) and the PG836 isolate (HS:10 serotype) have an LPS that bears a GD3 ganglioside-like structure and that OH4384 has an LPS that bears a GT1a-like structure. C. jejuni, including the Miller-Fisher syndrome-associated serotypes HS:2 and HS:23, had GT1a-like and GQ1b-like oligosaccharides (59).…”

“…To further investigate the role of structural mimicry in developing pathogenic autoantibodies, Goodyear et al (27) immunized mice with GT1a/GD3-like C. jejuni LPS and then developed a monoclonal antibody that reacted with both the immunizing LPS and GQ1b/GT1a/GD3 gangliosides. Immunohistological studies revealed binding of the antibodies to ganglioside-rich sites, including motor nerve terminals.…”

Autoantobodies activate small GTPase RhoA to modulate neurite outgrowth

“…8,17,18 Nerve repair/regeneration forms the basis of recovery in the majority of patients with GBS. Our group has focused on the pathophysiologic effects of anti-ganglioside Abs on nerve repair/regeneration (injured nerve fibers) for last few years keeping in view the patients with incomplete recovery and the following related clinical observations.…”