Guillain‐Barré Syndrome Animal Model: The First Proof of Molecular Mimicry in Human Autoimmune Disorder

Shahrizaila, Nortina; Yuki, Nobuhiro

doi:10.1155/2011/829129

Cited by 80 publications

(65 citation statements)

References 26 publications

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“…22 Several clinical patterns have since been described in association with certain anti-ganglioside antibodies. This includes the association of pure motor GBS with IgG anti-GM1/ GalNAc-GD1a antibodies 6 and IgG antibodies to Represents the single gangliosides and ganglioside complexes that showed a significant association with the electrodiagnostic subtypes.…”

Section: Resultsmentioning

confidence: 99%

Antibodies to single glycolipids and glycolipid complexes in Guillain-Barré syndrome subtypes

et al. 2014

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Objective: To comprehensively investigate the relationship between antibodies to single glycolipids and their complexes and Guillain-Barré syndrome subtypes and clinical features.Methods: In acute sera from 199 patients with Guillain-Barré syndrome, immunoglobulin G (IgG) antibodies to glycolipids and ganglioside complexes were tested using ELISA against individual antigens from single glycolipids including gangliosides (LM1, GM1, GM1b, GD1a, GalNAc-GD1a, GD1b, GT1a, GT1b, GQ1b) and a neutral glycolipid, asialo-GM1 (GA1), and antigens from the combination of 2 different glycolipids. Based on serial nerve conduction studies, the electrodiagnoses were as follows: 69 demyelinating subtype, 85 axonal subtypes, and 45 unclassified.Results: Significant associations were detected between acute motor axonal neuropathy subtype and IgG antibodies to GM1, GalNAc-GD1a, GA1, or LM1/GA1 complex. Reversible conduction failure was significantly associated with IgG antibodies to GM1, GalNAc-GD1a, GD1b, or complex of LM1/GA1. No significant association was demonstrated between acute inflammatory demyelinating polyneuropathy and any of the glycolipids or ganglioside complexes. Antiganglioside complex antibodies alone were detected in 7 patients (5 axonal subtype). Conclusions:The current study demonstrates that antibodies to single glycolipids and ganglioside complexes are associated with acute motor axonal neuropathy or acute motor conduction block neuropathy but not acute inflammatory demyelinating polyneuropathy. Classification of evidence:This study provides Class II evidence that antibodies to glycolipids are increased in patients with acute motor axonal neuropathy and acute motor conduction block neuropathy but not acute inflammatory demyelinating polyneuropathy. Neurology ® 2014;83:118-124 GLOSSARY AIDP 5 acute inflammatory demyelinating polyneuropathy; AMAN 5 acute motor axonal neuropathy; AMCBN 5 acute motor conduction block neuropathy; GBS 5 Guillain-Barré syndrome; GSC 5 ganglioside complex; Ig 5 immunoglobulin; NCS 5 nerve conduction study.Guillain-Barré syndrome (GBS) is an acute immune-mediated polyneuropathy with 2 major subtypes: acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonal neuropathy (AMAN).1 Within the axonal subtype, there are now recognized variants evident on nerve conduction studies (NCS), which demonstrate early reversible conduction failure, referred to as acute motor conduction block neuropathy (AMCBN).2 There is robust evidence that immunoglobulin G (IgG) anti-ganglioside antibodies are associated with the pathogenesis of AMAN, whereas the target antigens in AIDP remain elusive. The patients who were seronegative for antibodies to single gangliosides were found to have anti-GSC antibodies. The authors have since described further associations between anti-GSC antibodies and variants of GBS. This includes antibodies to LM1 and its complexes in AIDP, 5 to complex of GM1 and GalNAc-GD1a (GM1/GalNAc-GD1a) in AMCBN,6 and to complexes of GD1a/GD1b and GD1b/GT1b in pa...

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Section: Resultsmentioning

confidence: 99%

Antibodies to single glycolipids and glycolipid complexes in Guillain-Barré syndrome subtypes

et al. 2014

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“…In the realm of autoimmunity, similarity between self and pathogen has also been called molecular mimicry [9]; however this terminology does not allow for differentiation between different types of mimicry -structural (as in cross-reactive B cell epitopes), or mechanism-related (as in Epstein -Barr virus (EBV)'s adoption of IL-10 as a mediator of immune regulation [10]). In this article, we will specifically focus on T cell epitope redundancy, as defined below, which is one of the direct results of the TCR training on self in the thymus [11] and education of these T cells in the periphery [12].…”

Section: Tcr Degeneracy Epitope Redundancy Mimicry and Camouflagementioning

confidence: 99%

T cell epitope redundancy: cross-conservation of the TCR face between pathogens and self and its implications for vaccines and autoimmunity

Moise

Beseme

Tassone

et al. 2016

Expert Review of Vaccines

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SummaryT cells are extensively trained on 'self' in the thymus and then move to the periphery, where they seek out and destroy infections and regulate immune response to self-antigens. T cell receptors (TCR) on T cells' surface recognize T cell epitopes, short linear strings of amino acids presented by antigen-presenting cells. Some of these epitopes activate T effectors, while others activate regulatory T cells. It was recently discovered that T cell epitopes that are highly conserved on their TCR face with human genome sequences are often associated with T cells that regulate immune response. These TCR-cross-conserved or 'redundant epitopes' are more common in proteins found in pathogens that have co-evolved with humans than in other noncommensal pathogens. Epitope redundancy might be the link between pathogens and autoimmune disease. This article reviews recently published data and addresses epitope redundancy, the "elephant in the room" for vaccine developers and T cell immunologists.

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“…Molecular mimicry often occurs by design and manifests as a control during various regulatory mechanisms (4). It also occurs as an accidental encounter of structural resemblances, particularly in the immune system, sometimes culminating in pathological conditions such as autoimmune disorders (5)(6)(7)(8). The molecular mimicry between self and viral or bacterial peptides generally leads to the activation of self-reactive T cells resulting in autoimmune pathologies, for example, multiple sclerosis, autoimmune hepatitis, and myocarditis (9)(10)(11).…”

mentioning

confidence: 99%

Structural Evaluation of a Mimicry-Recognizing Paratope: Plasticity in Antigen–Antibody Interactions Manifests in Molecular Mimicry

Tapryal

Gaur

Kaur

et al. 2013

The Journal of Immunology

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Molecular mimicry manifests antagonistically with respect to the specificity of immune recognition. However, it often occurs because different Ags share surface topologies in terms of shape or chemical nature. It also occurs when a flexible paratope accommodates dissimilar Ags by adjusting structural features according to the antigenic epitopes or differential positioning in the Ag combining site. Toward deciphering the structural basis of molecular mimicry, mAb 2D10 was isolated from a maturing immune response elicited against methyl α-d-mannopyranoside and also bound equivalently to a dodecapeptide. The physicochemical evidence of this carbohydrate–peptide mimicry in the case of mAb 2D10 had been established earlier. These studies had strongly suggested direct involvement of a flexible paratope in the observed mimicry. Surprisingly, comparison of the Ag-free structure of single-chain variable fragment 2D10 with those bound to sugar and peptide Ags revealed a conformationally invariant state of the Ab while binding to chemically and structurally disparate Ags. This equivalent binding of the two dissimilar Ags was through mutually independent interactions, demonstrating functional equivalence in the absence of structural correlation. Thus, existence of a multispecific, mature Ab in the secondary immune response was evident, as was the plasticity in the interactions while accommodating topologically diverse Ags. Although our data highlight the structural basis of receptor multispecificity, they also illustrate mechanisms adopted by the immune system to neutralize the escape mutants generated during pathogenic insult.

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Guillain‐Barré Syndrome Animal Model: The First Proof of Molecular Mimicry in Human Autoimmune Disorder

Cited by 80 publications

References 26 publications

Antibodies to single glycolipids and glycolipid complexes in Guillain-Barré syndrome subtypes

Antibodies to single glycolipids and glycolipid complexes in Guillain-Barré syndrome subtypes

T cell epitope redundancy: cross-conservation of the TCR face between pathogens and self and its implications for vaccines and autoimmunity

Structural Evaluation of a Mimicry-Recognizing Paratope: Plasticity in Antigen–Antibody Interactions Manifests in Molecular Mimicry

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