title: Dissecting the Role of Anti-ganglioside Antibodies in Guillain-Barré Syndrome: an Animal Model Approach.
abstract: Guillain-Barré syndrome (GBS) is an autoimmune polyneuropathy disease affecting the peripheral nervous system (PNS). Most of the GBS patients experienced neurological symptoms such as paresthesia, weakness, pain, and areflexia. There are also combinations of non-neurological symptoms which include upper respiratory tract infection and diarrhea. One of the major causes of GBS is due largely to the autoantibodies against gangliosides located on the peripheral nerves. Gangliosides are sialic acid-bearing glycosphingolipids consisting of a ceramide lipid anchor with one or more sialic acids attached to a neutral sugar backbone. Molecular mimicry between the outer components of oligosaccharide of gangliosides on nerve membrane and lipo-oligosaccharide of microbes is thought to trigger the autoimmunity. Intra-peritoneal implantation of monoclonal ganglioside antibodies secreting hybridoma into animals induced peripheral neuropathy. Recent studies demonstrated that injection of synthesized anti-ganglioside antibodies raised by hybridoma cells into mice initiates immune response against peripheral nerves, and eventually failure in peripheral nerve regeneration. Accumulating evidences indicate that the conjugation of anti-ganglioside monoclonal antibodies to activating FcγRIII present on the circulating macrophages inhibits axonal regeneration. The activation of RhoA signaling pathways is also involved in neurite outgrowth inhibition. However, the link between these two molecular events remains unresolved and requires further investigation. Development of anti-ganglioside antagonists can serve as targeted therapy for the treatment of GBS and will open a new approach of drug development with maximum efficacy and specificity.
authors.affiliation: Department of Biomedical Sciences, City University of Hong Kong, Tat Chee Avenue, Hong Kong, People's Republic of China.
authors.forename: Pallavi
authors.initials: P
authors.lastname: Asthana
authors.affiliation: Department of Biomedical Sciences, City University of Hong Kong, Tat Chee Avenue, Hong Kong, People's Republic of China.
authors.forename: Joaquim Si Long
authors.initials: JS
authors.lastname: Vong
authors.affiliation: Department of Biomedical Sciences, City University of Hong Kong, Tat Chee Avenue, Hong Kong, People's Republic of China.
authors.forename: Gajendra
authors.initials: G
authors.lastname: Kumar
authors.affiliation: Laboratory of Neurodegenerative Diseases, School of Biomedical Sciences, LKS Faculty of Medicine, and State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Pokfulam, Hong Kong, People's Republic of China.
authors.forename: Raymond Chuen-Chung
authors.initials: RC
authors.lastname: Chang
authors.affiliation: Department of Neurology, University of Texas Medical School at Houston, 6431 Fannin Street, Houston, TX, 77030, USA.
authors.forename: Gang
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Department of Neurology, University of Texas Medical School at Houston, 6431 Fannin Street, Houston, TX, 77030, USA.
authors.forename: Kazim A
authors.initials: KA
authors.lastname: Sheikh
authors.affiliation: Department of Biomedical Sciences, City University of Hong Kong, Tat Chee Avenue, Hong Kong, People's Republic of China. eddiema@cityu.edu.hk.|Centre for Biosystems, Neuroscience, and Nanotechnology, City University of Hong Kong, Tat Chee Avenue, Hong Kong, People's Republic of China. eddiema@cityu.edu.hk.|State Key Laboratory in Marine Pollution, City University of Hong Kong, Tat Chee Avenue, Hong Kong, People's Republic of China. eddiema@cityu.edu.hk.
authors.forename: Chi Him Eddie
authors.initials: CH
authors.lastname: Ma
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D005732:Gangliosides / Q000097:blood / Q000276:immunology*; D020275:Guillain-Barre Syndrome / Q000097:blood / Q000276:immunology* / Q000628:therapy*; D006801:Humans; D007111:Immunity, Cellular / Q000502:physiology; D007167:Immunotherapy / Q000379:methods / Q000639:trends
chemical_list: D001323:Autoantibodies; D005732:Gangliosides
keywords: Anti-ganglioside complex; Fc receptor; Guillain-Barré syndrome; Monoclonal antibody; Peripheral nervous system