Abstract
Guillain-Barre syndrome (GBS), characterized by acute progressive limb weakness and areflexia, is the prototype of postinfectious autoimmune diseases. Campylobacter jejuni is the most frequently identified agent of infection in GBS patients, often preceding acute motor axonal neuropathy (AMAN), a variant of GBS. Anti-GM1, anti-GM1b, anti- GD1a, and anti-GalNAc-GD1a IgG antibodies are associated with AMAN. Carbohydrate mimicry [Galβ1-3GalNAcβ1- 4(NeuAcα 2-3)Galβ1-] was seen between the lipo-oligosaccharide of C. jejuni isolated from an AMAN patient and human GM1 ganglioside. Sensitization with the lipo-oligosaccharide of C. jejuni induces AMAN in rabbits as does sensitization with GM1 ganglioside. Paralyzed rabbits have pathological changes in their peripheral nerves identical to changes seen in human GBS. C. jejuni infection may induce anti-ganglioside antibodies by molecular mimicry, eliciting AMAN. This is the first verification of the causative mechanism of molecular mimicry in an autoimmue disease. To express ganglioside mimics, C. jejuni requires specific gene combinations that function in sialic acid biosynthesis or transfer. The knockout mutants of these landmark genes of GBS show reduced reactivity with GBS patients sera, and fail to induce an antiganglioside antibody response in mice. These genes are crucial for the induction of neuropathogenic cross-reactive antibodies. An approach for evaluating intravenous immune globulin, a treatment for GBS, based on our animal model of AMAN is also discussed in this review, and recent advances made in this field are described.
Keywords: Autoimmune disease, Campylobacter jejuni, ganglioside, Guillain-Barre syndrome, molecular mimicry
CNS & Neurological Disorders - Drug Targets
Title: Ganglioside Mimicry as a Cause of Guillain-Barre Syndrome
Volume: 5 Issue: 4
Author(s): Tomoko Komagamine and Nobuhiro Yuki
Affiliation:
Keywords: Autoimmune disease, Campylobacter jejuni, ganglioside, Guillain-Barre syndrome, molecular mimicry
Abstract: Guillain-Barre syndrome (GBS), characterized by acute progressive limb weakness and areflexia, is the prototype of postinfectious autoimmune diseases. Campylobacter jejuni is the most frequently identified agent of infection in GBS patients, often preceding acute motor axonal neuropathy (AMAN), a variant of GBS. Anti-GM1, anti-GM1b, anti- GD1a, and anti-GalNAc-GD1a IgG antibodies are associated with AMAN. Carbohydrate mimicry [Galβ1-3GalNAcβ1- 4(NeuAcα 2-3)Galβ1-] was seen between the lipo-oligosaccharide of C. jejuni isolated from an AMAN patient and human GM1 ganglioside. Sensitization with the lipo-oligosaccharide of C. jejuni induces AMAN in rabbits as does sensitization with GM1 ganglioside. Paralyzed rabbits have pathological changes in their peripheral nerves identical to changes seen in human GBS. C. jejuni infection may induce anti-ganglioside antibodies by molecular mimicry, eliciting AMAN. This is the first verification of the causative mechanism of molecular mimicry in an autoimmue disease. To express ganglioside mimics, C. jejuni requires specific gene combinations that function in sialic acid biosynthesis or transfer. The knockout mutants of these landmark genes of GBS show reduced reactivity with GBS patients sera, and fail to induce an antiganglioside antibody response in mice. These genes are crucial for the induction of neuropathogenic cross-reactive antibodies. An approach for evaluating intravenous immune globulin, a treatment for GBS, based on our animal model of AMAN is also discussed in this review, and recent advances made in this field are described.
Export Options
About this article
Cite this article as:
Komagamine Tomoko and Yuki Nobuhiro, Ganglioside Mimicry as a Cause of Guillain-Barre Syndrome, CNS & Neurological Disorders - Drug Targets 2006; 5 (4) . https://dx.doi.org/10.2174/187152706777950765
DOI https://dx.doi.org/10.2174/187152706777950765 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
Call for Papers in Thematic Issues
Diagnosis and treatment of central nervous system infectious diseases
Infectious diseases of the central nervous system (CNS) can be divided into bacterial, tuberculous, viral, fungal, parasitic infections, etc. Early etiological treatment is often the most crucial means to reduce the mortality rate of patients with central nervous system infections, reduce complications and sequelae, and improve prognosis. The initial clinical ...read more
Techniques of Drug Repurposing: Delivering a new life to Herbs & Drugs
Of late, with the adaptation of innovative approaches and integration of advancements made towards medical sciences as well as the availability of a wide range of tools; several therapeutic challenges are being translated into viable clinical solutions, with a high degree of efficacy, safety, and selectivity. With a better understanding ...read more
Trends and perspectives in the rational management of CNS disorders
Central nervous system (CNS) diseases enforce a significant global health burden, driving ongoing efforts to improve our understanding and effectiveness of therapy. This issue investigates current advances in the discipline, focusing on the understanding as well as therapeutic handling of various CNS diseases. The issue covers a variety of diseases, ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Animal Models to Investigate Pathomechanisms and Evaluate Novel Treatments for Autoimmune Bullous Dermatoses
Current Pharmaceutical Design The Immunosuppressive Role of Adenosine A2A Receptors in Ischemia Reperfusion Injury and Islet Transplantation
Current Diabetes Reviews Autoimmune Diseases and Atherosclerosis: The Inflammatory Connection
Current Immunology Reviews (Discontinued) Gastrointestinal Immune System and Brain Dialogue Implicated in Neuroinflammatory and Neurodegenerative Diseases
Current Molecular Medicine Imatinib Mesylate: An Innovation in Treatment of Autoimmune Diseases
Recent Patents on Inflammation & Allergy Drug Discovery Chronic Immune Stimulation Correlates with Reduced Phenylalanine Turnover
Current Drug Metabolism The Janus Face of CD4+CD25+ Regulatory T Cells in Cancer and Autoimmunity
Current Medicinal Chemistry Generation of Regulatory T Cells to Antigen Expressed in the Retina
Current Immunology Reviews (Discontinued) Apoptosis and Autoimmune Disease
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents Inhibitors Targeting the LFA-1/ICAM-1 Cell-Adhesion Interaction: Design and Mechanism of Action
Current Pharmaceutical Design Update on ICOS: A Possible Target for Turning-Off Autoimmunity
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Personalized Therapies in Pediatric Inflammatory and Autoimmune Diseases
Current Pharmaceutical Design Colon as Target for Drug Delivery
Current Drug Therapy Identification of Expressed miRNAs in Human Rheumatoid Arthritis Using Computational Approach – Discovery of a New miR-7167 from Human
MicroRNA Tissue-specific Glucocorticoid Signaling May Determine the Resistance Against Glucocorticoids in Autoimmune Diseases
Current Medicinal Chemistry Animal Models of Lupus and Lupus Nephritis
Current Pharmaceutical Design HSP60 as a Drug Target
Current Pharmaceutical Design Micronutrients at the Interface Between Inflammation and Infection Ascorbic Acid and Calciferol. Part 2: Calciferol and the Significance of Nutrient Supplements
Inflammation & Allergy - Drug Targets (Discontinued) Comparative Genomics for the Investigation of Autoimmune Diseases
Current Pharmaceutical Design Interferon: Cellular Executioner or White Knight?
Current Medicinal Chemistry