An anti-ganglioside antibody-secreting hybridoma induces neuropathy in mice.
Immune responses against gangliosides are strongly implicated in the pathogenesis of some variants of Guillain-Barré syndrome (GBS). For example, IgG antibodies against GM1, GD1a, and related gangliosides are frequently present in patients with post-Campylobacter acute motor axonal neuropathy (AMAN) variant of GBS, and immunization of rabbits with GM1 has produced a model of AMAN. However, the role of anti-ganglioside antibodies in GBS continues to be debated because of lack of a passive transfer model. We recently have raised several monoclonal IgG anti-ganglioside antibodies. We passively transfer these antibodies by intraperitoneal hybridoma implantation and by systemic administration of purified anti-ganglioside antibodies in mice. Approximately half the animals implanted with an intraperitoneal clone of anti-ganglioside antibody-secreting hybridoma developed a patchy, predominantly axonal neuropathy affecting a small proportion of nerve fibers. In contrast to hybridoma implantation, passive transfer with systemically administered anti-ganglioside antibodies did not cause nerve fiber degeneration despite high titre circulating antibodies. Blood-nerve barrier studies indicate that animals implanted with hybridoma had leaky blood-nerve barrier compared to mice that received systemically administered anti-ganglioside antibodies. Our findings suggest that in addition to circulating antibodies, factors such as antibody accessibility and nerve fiber resistance to antibody-mediated injury play a role in the development of neuropathy.
Department of Neurology, Johns Hopkins Medical Institutions, Baltimore, MD 21205, USA. ksheik@jhmi.edu
Kazim A
KA
Sheikh
Gang
G
Zhang
Yanpin
Y
Gong
Ronald L
RL
Schnaar
John W
JW
Griffin
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood; D000917:Antibody Formation; D001812:Blood-Brain Barrier / Q000378:metabolism; D015153:Blotting, Western / Q000379:methods; D002199:Capillary Permeability / Q000502:physiology; D004195:Disease Models, Animal; D005677:G(M1) Ganglioside / Q000276:immunology; D005732:Gangliosides / Q000276:immunology*; D006825:Hybridomas / Q000276:immunology*; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000009:adverse effects; D007150:Immunohistochemistry / Q000379:methods; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology; D010525:Peripheral Nerves / Q000473:pathology / Q000648:ultrastructure; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000473:pathology; D013045:Species Specificity; D013116:Spinal Cord / Q000033:anatomy & histology / Q000378:metabolism
D000911:Antibodies, Monoclonal; D005732:Gangliosides; D007074:Immunoglobulin G; D019394:Ki-67 Antigen; C021298:ganglioside, GD1a; D005677:G(M1) Ganglioside