Acute motor axonal neuropathy with high titer IgG and IgA anti-GD1 a antibodies following Campylobacter enteritis

Ragno, Michele; Torrieri, Filomena; Guglielmo, Giovanni; Fermani, P.; Uncini, Antonino

doi:10.1016/s0022-510x(96)05349-x

Cited by 38 publications

(18 citation statements)

References 42 publications

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“…In the US patients studied, high titers of IgG anti-GD1a antibodies were found in 1 of the 2 axonal cases but in none of the AIDP cases. Although case reports have suggested that IgG anti-GD1a can occur in GBS, [32][33][34][35][36] most studies have not found this association. 13,14,16,37 We suggest the association between AMAN and IgG anti-GD1a was not recognized, as most studies involved GBS populations consisting predominantly, if not exclusively, of AIDP patients.…”

Section: Discussionmentioning

confidence: 97%

Anti-GD1a antibody is associated with axonal but not demyelinating forms of Guillain-Barr� syndrome

et al. 1999

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Immunopathological studies suggest that the target of immune attack is different in the subtypes of Guillain‐Barré syndrome (GBS). In acute motor axonal neuropathy (AMAN), the attack appears directed against the axolemma and nodes of Ranvier. In acute inflammatory demyelinating polyneuropathy (AIDP), the attack appears directed against a component of the Schwann cell. However, the nature of the antigenic targets is still not clear. We prospectively studied 138 Chinese GBS patients and found that IgG anti‐GD1a antibodies were closely associated with AMAN but not AIDP. With a cutoff titer of greater than 1:100, 60% of AMAN versus 4% of AIDP patients had IgG anti‐GD1a antibodies; with a cutoff titer of greater than 1:1,000, 24% of AMAN patients and none of the AIDP patients had IgG anti‐GD1a antibodies. In contrast, low levels of IgG anti‐GM1 antibodies (>1:100) were detected in both the AMAN and the AIDP forms (57% vs 35%, NS). High titers of IgG anti‐GM1 (>1:1,000) were more common in the AMAN form (24% vs 8%, NS). Serological evidence of recent Campylobacter infection was detected in 81% of AMAN and 50% of AIDP patients, and anti‐ganglioside antibodies were common in both Campylobacter‐infected and noninfected patients. Our results suggest that IgG anti‐GD1a antibodies may be involved in the pathogenesis of AMAN. Ann Neurol 1999;45:168–173

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Section: Discussionmentioning

confidence: 97%

Anti-GD1a antibody is associated with axonal but not demyelinating forms of Guillain-Barr� syndrome

et al. 1999

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“…The acute motor axonal neuropathy (AMAN) variant, in which only motor axons are affected, is characterized by the presence of serum anti-GD1a ganglioside antibodies (Abs) (Lugaresi et al, 1997;Ho et al, 1999;Ogawara et al, 2000;Ilyas et al, 2001). Clinical and pathological evidence indicates multiple locations as potential sites of injury, including the nodes of Ranvier , ventral roots and distal nerves (Feasby et al, 1986), and motor nerve terminals (Ho et al, 1997;Kuwabara et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Overexpression of GD1a Ganglioside Sensitizes Motor Nerve Terminals to Anti-GD1a Antibody-Mediated Injury in a Model of Acute Motor Axonal Neuropathy

et al. 2005

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Anti-GD1a ganglioside antibodies (Abs) are the serological hallmark of the acute motor axonal form of the post-infectious paralysis, Guillain-Barré syndrome. Development of a disease model in mice has been impeded by the weak immunogenicity of gangliosides and the apparent resistance of GD1a-containing neural membranes to anti-GD1a antibody-mediated injury. Here we used mice with altered ganglioside biosynthesis to generate such a model at motor nerve terminals. First, we bypassed immunological tolerance by immunizing GD1a-deficient, ␤-1,4-N-acetylgalactosaminyl transferase knock-out mice with GD1a ganglioside-mimicking antigens from Campylobacter jejuni and generated high-titer anti-GD1a antisera and complement fixing monoclonal Abs (mAbs). Next, we exposed ex vivo nerve-muscle preparations from GD1a-overexpressing, GD3 synthase knock-out mice to the anti-GD1a mAbs in the presence of a source of complement and investigated morphological and electrophysiological damage. Dense antibody and complement deposits were observed only over presynaptic motor axons, accompanied by severe ultrastructural damage and electrophysiological blockade of motor nerve terminal function. Perisynaptic Schwann cells and postsynaptic membranes were unaffected. In contrast, normal mice were not only unresponsive to immunization with GD1a but also resistant to neural injury during anti-GD1a Ab exposure, demonstrating the central role of membrane antigen density in modulating both immune tolerance to GD1a and axonal susceptibility to anti-GD1a Abmediated injury. Identical paralyzing effects were observed when testing mouse and human anti-GD1a-positive sera. These data indicate that anti-GD1a Abs arise via molecular mimicry and are likely to be clinically relevant in injuring peripheral nerve axonal membranes containing sufficiently high levels of GD1a.

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“…It is associated with a wide range of precipitating bacterial and viral infections, including Campylobacter jejuni enteritis in 10 to 50% of cases depending on geographical region (5,30,46). In addition to immune responses specific to the preceding infection, 40% of postCampylobacter infection GBS sera contain transient immunoglobulin M (IgM), IgA, and IgG antibodies to a variety of self gangliosides, including GM1, GM2, GD1a, GalNAc-GD1a, GD1b, GD3, GT1a, and GQ1b, which are believed to be among the principal pathogenic factors (7,8,28,37,65). Gangliosides are a family of sialic-acid-containing glycosphingolipids distributed throughout the body but highly enriched in the nervous system, where they are capable of acting as targets for anti-ganglioside autoantibodies (22,34,35,60).…”

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confidence: 99%

Tolerance to Self Gangliosides Is the Major Factor Restricting the Antibody Response to Lipopolysaccharide Core Oligosaccharides inCampylobacter jejuniStrains Associated with Guillain-Barré Syndrome

et al. 2002

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Guillain-Barré syndrome followingCampylobacter jejuni infection is frequently associated with anti-ganglioside autoantibodies mediated by molecular mimicry with ganglioside-like oligosaccharides on bacterial lipopolysaccharide (LPS). The regulation of antibody responses to these T-cell-independent antigens is poorly understood, and only a minority of Campylobacter-infected individuals develop anti-ganglioside antibodies. This study investigates the response to gangliosides and LPS in strains of mice by using a range of immunization strategies. In normal mice following intraperitoneal immunization, antibody responses to gangliosides and LPS are low level but can be enhanced by the antigen format or coadministration of protein to recruit T-cell help. Class switching from the predominant immunoglobulin M (IgM) response to IgG3 occurs at low levels, suggesting B1-cell involvement. Systemic immunization results in poor responses. In GalNAc transferase knockout mice that lack all complex gangliosides and instead express high levels of GM3 and GD3, generation of anti-ganglioside antibodies upon immunization with either complex gangliosides or gangliosidemimicking LPS is greatly enhanced and exhibits class switching to T-cell-dependent IgG isotypes and immunological memory, indicating that tolerance to self gangliosides is a major regulatory factor. Responses to GD3 are suppressed in knockout mice compared with wild-type mice, in which responses to GD3 are induced specifically by GD3 and as a result of polyclonal B-cell activation by LPS. The anti-ganglioside response generated in response to LPS is also dependent on the epitope density of the ganglioside mimicked and can be further manipulated by providing secondary signals via lipid A and CD40 ligation.

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Acute motor axonal neuropathy with high titer IgG and IgA anti-GD1 a antibodies following Campylobacter enteritis

Cited by 38 publications

References 42 publications

Anti-GD1a antibody is associated with axonal but not demyelinating forms of Guillain-Barr� syndrome

Anti-GD1a antibody is associated with axonal but not demyelinating forms of Guillain-Barr� syndrome

Overexpression of GD1a Ganglioside Sensitizes Motor Nerve Terminals to Anti-GD1a Antibody-Mediated Injury in a Model of Acute Motor Axonal Neuropathy

Tolerance to Self Gangliosides Is the Major Factor Restricting the Antibody Response to Lipopolysaccharide Core Oligosaccharides inCampylobacter jejuniStrains Associated with Guillain-Barré Syndrome

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