About two thirds of GBS cases occur after a respiratory or gastrointestinal infection, and the pathogen can be identified in about half of these cases [15]. Some of the more common preceding infections include C. jejuni cytomegalovirus, Epstein-Barr virus, Mycoplasma pneumonia, Hemophilus influenza, influenza A, and hepatitis E virus [2]. The best explanation for the association of GBS and aforementioned infections is molecular mimicry between the components of pathogens and axonal or myelin structures. C. jejuni is the most common antecedent infection in GBS, ranging from 26 to 65% of the cases depending on the geographic location [4]. Patients with AMAN after C. jejuni infection have high titers of antibodies to GM1 and GD1a, which is the result of cross-reactivity between lipo-oligosaccharides from the bacterial wall of C. jejuni and respective gangliosides of the motor nerve axons [16, 17]. On the other hand, lipo-oligosaccharides that mimic the carbohydrate moiety of peripheral nerve gangliosides are expressed in only a subset of C. jejuni strains, Penner D: 19 serogroup, as it is different from other serotypes in containing genes for enzymes involved in synthesis of sialic acids which result in molecular mimicry with gangliosides GM1, GD1a ND GD1B [1]. As a result, GBS is a relatively rare outcome of these infections: e.g., only one out of 5000 C. pylori gastroenteritis results in GBS [18]. Whether C. jejuni infection is a cause of AIDP is a matter of controversy. A previous study showed that only 5 of 22 (23%) of patients with GBS post C. jejuni infection had AIDP, but when they were followed by repeated nerve conduction studies, all of those who had prolonged motor distal latencies normalized in less than 2 weeks suggestive for impaired axonal conductivity (seen in AMAN) rather than segmental demyelination seen in AIDP, which is associated with more slowing of the nerve conduction study in the same time period during remyelination [19]. A neuropathy characterized by severe axonal degeneration and seropositivity for IgG or IgM GM1 antibodies has also been reported in patients who received ganglioside injections for chronic pain [20]. IgG antibodies against GQ1b and GD1a are detected in more than 90% of patients with MFS [2123], as well as patients with AIDP who have ophthalmoplegia. As about half of patients with pharyngeal-cervical-brachial variants are seropositive for IgG anti- GT1a antibodies which cross-reacts with GQ1b, it is considered to be in the broad spectrum of MFS [7].

Differences in anatomical expression of gangliosides explain the diverse phenotypic manifestations of GBS variants. GM1 is suggested to be expressed more in the motor than sensory nerve roots, therefore providing possible explanation for motor involvement of AMAN [23]. On the other hand, GM1/GD1a is also present in the sensory nerves [24]. The predominant or pure motor involvement could be the result of specificity of autoantibodies for epitopes of these gangliosides that are only present in the motor axons. Furthermore, nodes of Ranvier of the distal, intramuscular portion of the motor axons are suggested to be particularly susceptible to complement activation by antibodies to GD1a [25]. The blood-nerve barrier is more permeable in the unmyelinated distal branches of the motor nerves and the nerve roots, making these parts of the peripheral nerves more vulnerable to circulating factors such as autoantibodies and complement [26, 27]. Ophthalmoplegia and areflexia in MFS which is associated with antibodies directed to GQ1b are explained by high expression of GQ1b in the oculomotor nerves and muscle spindles [23].

The autoantigen involved in AIDP is so far unknown, and most of the AIDP patients are not seropositive for antiganglioside antibodies. Some of the putative antigens include proteins which are expressed at the nodes of Ranvier (neurofascin 186, gliomedin, sodium channels, ankyrin, and spectrin) and at the paranode (neu- rofascin 155, contactin/Caspr 1, and connexins Cx31.3, Cx3232) [23].

A recently identified molecular target is moesin in patients with CMV infection as antibodies against moesin were present in most of AIDP cases after CMV but not with other GBS patients or other neurological disease controls [28]. Moesin is expressed in the microvilli of the Schwann cells and has been proposed to have a critical role in myelination [29].

There is also evidence for involvement of T cells in the pathogenesis of GBS, based on: (1) T cell infiltration is present in experimental allergic neuritis (EAN) which is considered as an animal model of GBS. (2) There is increased frequency of Th1 and Th17 levels in the blood and of T cell-related cytokines (IFN gamma, IL-17, and IL-22) in the cerebrospinal fluid of GBS patients [30-32]. (3) Reduced number and abnormal function of CD4+Foxp3+ (Treg) cells, which have a critical role in immune homeostasis, have been demonstrated in the blood of GBS patients [32, 33].

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