Anti-GM1/GD1b M-proteins damage human spinal cord neurons co-cultured with muscle.
IgM M-proteins in some motor neuron disease (MND) patients bind immunologically to shared determinants on gangliosides GM1 and GD1b. Since patients with these M-proteins have improved with immunotherapy the antibodies may be important in the pathogenesis of MND. To study how the M-proteins might damage motor neurons, we established co-cultures of human neurons from spinal cord explants and human myotubes. Antibodies from patient but not control serum bound to the cultured neurons. Neurons in co-cultures degenerated after incubation with patient but not control serum. These results demonstrate that anti-GM1 antibodies can bind to and destroy spinal cord neurons that are cultured with muscle. Nerve-muscle co-cultures can serve as a system to examine effects of anti-GM1/GD1b M-proteins on motor neurons.
Heiman-Patterson
T
T
Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107.
Krupa
T
T
Thompson
P
P
Nobile-Orazio
E
E
Tahmoush
A J
AJ
Shy
M E
ME
D001665:Binding Sites; D002240:Carbohydrate Sequence; D002450:Cell Communication; D002478:Cells, Cultured; D005333:Fetus; D005677:G(M1) Ganglioside / Q000276:immunology*; D005732:Gangliosides / Q000276:immunology*; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood / Q000378:metabolism / Q000633:toxicity*; D008875:Middle Aged; D008969:Molecular Sequence Data; D016472:Motor Neuron Disease / Q000097:blood / Q000276:immunology*; D009132:Muscles / Q000502:physiology*; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000473:pathology; D010266:Paraproteins / Q000378:metabolism / Q000633:toxicity*; D013116:Spinal Cord / Q000166:cytology*
D005732:Gangliosides; D007075:Immunoglobulin M; D010266:Paraproteins; C033851:ganglioside, GD1b; D005677:G(M1) Ganglioside