TY - JOUR
T1 - Dissecting the Role of Anti-ganglioside Antibodies in Guillain-Barré Syndrome
T2 - an Animal Model Approach
AU - Asthana, Pallavi
AU - Vong, Joaquim Si Long
AU - Kumar, Gajendra
AU - Chang, Raymond Chuen Chung
AU - Zhang, Gang
AU - Sheikh, Kazim A.
AU - Ma, Chi Him Eddie
N1 - Funding information:
This work is supported in part by The Health and Medical Research Fund (HMRF), Food and Health Bureau, Hong Kong Special Administrative Region Government (ref. no. 01122016, 01122026, and 12134101) and ECS/GRF grants from the Research Grant Council of the Hong Kong Special Administrative Region Government (CityU 161212, CityU 160813, and CityU 11100015).
Publisher Copyright:
© 2015, Springer Science+Business Media New York.
PY - 2016/9
Y1 - 2016/9
N2 - 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.
AB - 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.
KW - Anti-ganglioside complex
KW - Fc receptor
KW - Guillain-Barré syndrome
KW - Monoclonal antibody
KW - Peripheral nervous system
UR - http://www.scopus.com/inward/record.url?scp=84941712001&partnerID=8YFLogxK
U2 - 10.1007/s12035-015-9430-9
DO - 10.1007/s12035-015-9430-9
M3 - Review article
C2 - 26374552
AN - SCOPUS:84941712001
SN - 0893-7648
VL - 53
SP - 4981
EP - 4991
JO - Molecular Neurobiology
JF - Molecular Neurobiology
IS - 7
ER -