Dissecting the Role of Anti-ganglioside Antibodies in Guillain-Barré Syndrome: an Animal Model Approach
Autor(es): Asthana Pallavi,Vong Joaquim Si Long,Kumar Gajendra,Chang Raymond Chuen-Chung,Zhang Gang,Sheikh Kazim A,Ma Chi Him Eddie
Resumo: 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 Fc?RIII 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.
Palavras-Chave: Anti-ganglioside complex; Fc receptor; Guillain-Barré syndrome; Monoclonal antibody; Peripheral nervous system
Imprenta: Molecular Neurobiology, v. 53, n. 7, p. 4981-4991, 2015
Identificador do objeto digital: 10.1007/s12035-015-9430-9
Descritores: Guillain-Barre Syndrome - Cell ; Guillain-Barre Syndrome - Immune response ; Guillain-Barre Syndrome - Antibodies ; Guillain-Barre Syndrome - Autoimmunity
Data de publicação: 2015