Cross-reactive antibodies against GM2 and CMV-infected fibroblasts in Guillain–Barré syndrome

Ang, C. Wim; Jacobs, Bart C.; Brandenburg, A. H.; Laman, Jon D.; Meché, F. G. A. Van Der; Osterhaus, A.D.M.E.; Doorn, Pieter A. van

doi:10.1212/wnl.54.7.1453

Cited by 77 publications

(43 citation statements)

References 32 publications

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“…Viral agents are hypothesized to lead to anti-ganglioside response via presentation of host ganglioside during viral budding from infected cells (Evans and Webb, 1986;Ang et al, 2000). The characteristics and pathological properties of our anti-GD1a antibodies and antisera arising in response to GD1a-KLH immunization were very similar to those seen in response to LOS immunization.…”

Section: Discussionmentioning

confidence: 56%

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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Section: Discussionmentioning

confidence: 56%

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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“…The implication of antiganglioside GM2 antibodies in the pathogenesis of GBS related to CMV has been described [15] . It has been demonstrated that CMV-infected fibroblasts express ganglioside-like epitopes that specifically recognize anti-GM2 antibodies [16] . These results suggest that, in CMVinfected GBS patients, infected cells with CMV can express epitopes inducing an immune response against gangliosides.…”

Section: Discussionmentioning

confidence: 99%

Guillain-Barré syndrome following hepatitis E

Loly¹,

Rikir²,

Seivert³

et al. 2009

WJG

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Guillain-Barré syndrome (GBS) is often triggered by a preceding bacterial or viral infection. Occasionally, it has been observed in association with acute hepatitis A, B and C, and three cases have been previously described in India in which GBS was associated with acute hepatitis E. A molecular mimicry mechanism is supposed to be involved in the pathogenesis of GBS triggered by infectious agents, although the nature of the shared epitopes has not been characterized in most instances, including that in the case of hepatotropic viruses. We report a case of GBS following acute hepatitis E in a European individual. The presence of antiganglioside GM2 antibodies in this patient suggested molecular mimicry involving ganglioside GM2 in the pathogenesis of GBS associated with hepatitis E.

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“…The preceding infections with CMV, EBV, and Campylobacter jejuni in patients with the syndrome have been reported to be associated with severe axonal degeneration and presence of anti-ganglioside antibodies [Hughes et al, 1999;Hadden et al, 2001;Yuki, 2001]. Generation of anti-ganglioside antibodies has been attributed to molecular mimicry between the epitopes of the infecting pathogen and/or epitopes expressed by infected cells [Shimoya et al, 1997;Ang et al, 2000]. In the present case there was no recent infection with CMV, EBV and also of the clinical features of Campylobacter enteritis.…”

Section: Discussionmentioning

confidence: 99%

Case report: Hepatitis A preceding Guillain–Barré Syndrome

et al. 2006

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A case of acute hepatitis A with Guillain-Barré Syndrome subtype AMAN (acute motor axonal neuropathy) in a 17-year-old male is reported. Serum and cerebrospinal fluid were positive for anti-hepatitis A virus (HAV) IgM, IgG, and IgA. The onset of the syndrome was evident in week 3 of illness. The remarkably high titers of serum anti-HAV IgG appeared unique to a hepatitis A patient with the syndrome. Phylogenetic analysis of the HAV genome detected in the serum and feces revealed genotype IIIA, circulating commonly in Pune, western India.

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Cross-reactive antibodies against GM2 and CMV-infected fibroblasts in Guillain–Barré syndrome

Cited by 77 publications

References 32 publications

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

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

Guillain-Barré syndrome following hepatitis E

Case report: Hepatitis A preceding Guillain–Barré Syndrome

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