Ganglioside mimicry and peripheral nerve disease

Abstract

Four criteria must be satisfied to conclude that a given microorganism causes Guillain-Barré (GBS) or Fisher (FS) syndrome associated with anti-ganglioside antibodies: (1) an epidemiological association between the infecting microbe and GBS or FS; (2) isolation in the acute progressive phase of illness of that microorganism from GBS or FS patients with associated anti-ganglioside IgG antibodies; (3) identification of a microbial ganglioside mimic; and (4) a GBS or FS with associated anti-ganglioside antibodies model produced by sensitization with the microbe itself or its component, as well as with ganglioside. Campylobacter jejuni is a definitive causative microorganism of acute motor axonal neuropathy and may cause FS and related conditions. Haemophilus influenzae and Mycoplasma pneumoniae are possible causative microorganisms of acute motor axonal neuropathy or FS. Acute and chronic inflammatory demyelinating polyneuropathies may be produced by mechanisms other than ganglioside mimicry.

Molecular mimicry in neurological disease: what is the evidence?

“…Cytomegalovirus (CMV), EBV or Mycoplasma pneumoniae infection precedes the development of disease in a proportion of these patients [44,47,48]. The acute motor axonal neuropathy (AMAN) form (which is more common in Japan and Asia) [12,44,47,48] and the Fisher syndrome (FS, which is clinically characterized by ophthalmoplegia, ataxia and areflexia) are associated with infection with Campylobacter jejuni (C. jejuni) and antibody attack directed at peripheral nervous system axons at several sites, including the axolemma, nodes of Ranvier or pre-synaptic nerve terminal of the neuromuscular junction (NMJ) [12, 31, 45, 49 -52].…”

“…One subtype, known as acute inflammatory demyelinating polyneuropathy (AIDP) is associated with T lymphocytes, antibody formation and macrophages directed toward Schwann cells or myelin, resulting in demyelination and peripheral nervous system dysfunction [44]. AIDP is the most frequent clinical presentation of GBS, particularly in the western hemisphere [12,45,47]. Cytomegalovirus (CMV), EBV or Mycoplasma pneumoniae infection precedes the development of disease in a proportion of these patients [44,47,48].…”

“…These patients develop the acute onset of flaccid paralysis with variable amounts of sensory and autonomic dysfunction associated with antecedent infection [12,31,44,45]. Immune attack of the peripheral nervous system targets, either Schwann cells (myelin-producing cells) or axons thought to cause GBS [12, 44 -46].…”

“…To implicate molecular mimicry in the pathogenesis of disease, the following traditional criteria are generally accepted: (1) there is linear or conformational homology of a peptide between an environmental agent and self-antigen, (2) there is a cellular and/or antibody-mediated immune response directed to the homologous peptide, (3) the immune response is present in patients with disease and absent or reduced in patients without disease, (4) the immune response to the homologous peptide results in organ-specific damage and (5) the organ specific damage results in disease. Other corollaries that support the existence of molecular mimicry include: epidemiological data linking infection exposure to the neurological disease [3, 11,12], evidence that the immune response contributes to the pathology of the disease process [11,12], data showing mimicking epitopes are not random but include functionally significant regions of a molecule [4, 8,13], data showing that the phenotype of the T cell reaction directed at the infecting agent is identical to that directed at the autoantigen [7] and animal models that closely mimic human disease [2, 5, 12, 14 -16]. Although there is a vast amount of data showing cross-reactivity between infectious agents and host antigens, only recently have experiments been performed that strongly suggest that these cross-reactive immune reactions damage nervous system targets.…”

Campylobacterbacteremia: A rare and under-reported event?

“…A variety of post-infectious complications, including reactive arthritis (RA), Guillain-Barré syndrome (GBS) and Miller Fisher syndrome (MFS), have been associated with Campylobacter infections [31][32][33][34][35], with the latter two syndromes being linked to the expression of ganglioside mimics on the lipo-oligosaccharide (LOS) structures of certain C. jejuni strains. Essentially, upon infection, certain bacterial ganglioside mimics may facilitate the development of auto-antibodies to ganglioside structures present on the neurons of the host, leading to a temporary infection-associated paralysis [33].…”