Campylobacteriosis is a frequent antecedent event in Guillain-Barré syndrome (GBS), inducing high-titer serum antibodies for ganglioside antigens in the peripheral nervous system (PNS). Molecular mimicry between the lipooligosaccharide (LOS) component of Campylobacter jejuni and human peripheral nerve gangliosides is believed to play an important role in the pathogenesis of GBS. Conventional treatment strategies for patients with GBS include plasmapheresis, intravenous immunoglobulin (IVIG), and immunosuppression, which are invasive or relatively ineffective. In this study, we used our animal model of GBS, in which Lewis rats were immunized with GD3-like LOS isolated from C. jejuni. The animals developed anti-GD3 ganglioside antibodies and manifested neuromuscular dysfunction. To develop novel therapeutic strategies, we treated the animals by intraperitoneal administration of an anti-GD3 antiidiotype monoclonal antibody (BEC2) that specifically interacts with the pathogenic antibody. The treated animals had a remarkable reduction of anti-GD3 antibody titers and improvement of motor nerve functions. The results suggest that ganglioside mimics, such as antiidiotype antibodies, may be powerful reagents for therapeutic intervention in GBS by neutralizing specific pathogenic antiganglioside antibodies.
Keywordsganglioside; Campylobacter jejuni; Guillain-Barré; syndrome; lipooligosaccharide; GD3 ganglioside; anti-idiotype antibody Guillain-Barré syndrome (GBS) is an immune-mediated peripheral neuropathy characterized by neuromuscular weakness and frequently accompanied by flaccid paralysis and may occasionally lead to death. The major pathological hallmarks involve demyelination, axonal degeneration, and/or impairment of neurotransmission by ion channel blockage (Rinaldi and Willison, 2008;van Doorn et al., 2008;Kaida et al., 2009 immune responses triggered by an infectious agent or vaccination allow disease development and the underlying pathogenetic mechanisms (Langmuir et al., 1984;Kuwabara, 2004;Souayah et al., 2007). The most commonly identified microbial agents are Campylobacter jejuni (C. jejuni), Haemophilus influenzae, cytomegalovirus (CMV), Epstein-Barr virus, and Mycoplasma pneumoniae (Hughes et al., 1999;Hadden et al., 2001;Sivadon-Tardy et al., 2006. A preceding infectious event and patient-related host factors also seem to be related to certain subtypes of GBS and may affect the severity of the disease (Geleijns et al., 2005;Caporale et al., 2006;Yuki, 2007). C. jejuni infection frequently induces antiganglioside antibodies in the patient's serum (Yuki et al., 1990;Usuki et al., 2006b). Thus, despite the possibility of other pathogenic mechanisms, an antibodymediated process is one of the major insults to the nerve, causing both conduction block and velocity loss and the ensuing clinical symptoms (Rinaldi and Willison, 2008;van Doorn et al., 2008;Kaida et al., 2009).The etiology of GBS has been not been fully clarified; one possibility is based on molecular mimicry and cross-reacting antiglycolip...