Anti-GM(2) IgM antibody-induced complement-mediated cytotoxicity in patients with dysimmune neuropathies.
Anti-GM2 IgM antibodies have been reported in some patients with dysimmune neuropathy or lower motor neuron syndrome. To determine whether these antibodies can induce complement-dependent cytolysis we performed a cytotoxicity assay on neuroblastoma cells with sera from seven patients with demyelinating dysimmune neuropathies and high titers of anti-GM2 IgM. As controls we used sera from seven patients with other anti-neural reactivities, six with the same neuropathies but no anti-GM2 or other anti-neural reactivity and from eight normal subjects. Of the seven positive sera tested, six induced complement-mediated cytotoxicity, while none of the controls had any relevant effect on neuroblastoma cells. Preincubation of positive sera with purified GM2 removed cytotoxic activity. Affinity purified anti-GM2 IgM had the same cytotoxic anti-GM2 effect of whole serum while serum or complement alone did not have any effect. In four anti-GM2-positive patients the percentage of cell lysis correlated with anti-GM2 titers and with IgM staining of neuroblastoma cells while in two the cytotoxic effect was higher than expected from antibody titers. Complement-mediated cell lysis induced by anti-GM2 IgM antibodies may be a possible mechanism of neural damage in patients with dysimmune neuropathy and high titers of anti-GM2 IgM antibodies.
Giorgio Spagnol Service of Clinical Neuroimmunology, Milan, Italy.
B
B
Cavanna
H
H
Jiang
S
S
Allaria
M
M
Carpo
G
G
Scarlato
E
E
Nobile-Orazio
D002846:Chromatography, Affinity; D003167:Complement Activation / Q000276:immunology*; D005678:G(M2) Ganglioside / Q000276:immunology*; D020275:Guillain-Barre Syndrome / Q000276:immunology*; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology* / Q000302:isolation & purification; D016472:Motor Neuron Disease / Q000276:immunology*; D009447:Neuroblastoma; D014407:Tumor Cells, Cultured
D007075:Immunoglobulin M; D005678:G(M2) Ganglioside