Harmful effects of anti-GalNAc-GD1a antibodies and TNF-alpha on rat dorsal root ganglia.
The clinical characteristics of five (22%) of 23 patients with Guillain-Barré syndrome (GBS), whose serum contained immunoglobulin G (IgG) antibodies to the ganglioside N-acetylgalactosaminyl GD1a (GalNAc-GD1a), included pure motor weakness of the axonal type. These patients had a relatively good prognosis, but displayed higher serum tumor necrosis factor-alpha (TNF-alpha) titers than the other GBS patients. We examined the effect of serum from these patients with IgG anti-GalNAc-GD1a antibodies on neurites from cultured rat dorsal root ganglia (DRG) and found it to damage the myelin in well-elongated DRG neurites and monolayer cultures of Schwann cells and neurons. In the regeneration model, serum from these patients delayed neurite extension and inhibited Schwann cell proliferation. Neurons in cultured monolayers showed vacuolation and decreased rapidly in number. Schwann cells were also vacuolated and readily detached from the substratum. The effects of IgG anti-GalNAc-GD1a antibodies purified from one of the patients, rabbit serum after immunization with GalNAc-GD1a, and recombinant TNF-alpha were also examined. IgG anti-GalNAc-GD1a antibodies mainly inhibited the regeneration and preservation of neurons, while TNF-alpha mainly induced morphological changes in well-proliferated Schwann cells and myelin.
Kamakura
Keiko
K
Third Department of Internal Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan. kkmkrtng@ndmc.ac.jp
Kaida
Ken-ichi
K
Kusunoki
Susumu
S
Miyamoto
Norikazu
N
Masaki
Toshihiro
T
Nakamura
Ryohji
R
Motoyoshi
Kazuo
K
Fukuda
Jun
J
D000293:Adolescent; D000328:Adult; D000818:Animals; D000831:Animals, Newborn; D000888:Antibodies, Anti-Idiotypic / Q000633:toxicity*; D002648:Child; D002855:Chromatography, Thin Layer / Q000379:methods; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005455:Fluorescent Antibody Technique / Q000379:methods; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects*; D005732:Gangliosides / Q000097:blood / Q000276:immunology*; D020275:Guillain-Barre Syndrome / Q000097:blood / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D004676:Myelin Basic Protein / Q000378:metabolism; D009186:Myelin Sheath / Q000187:drug effects; D016501:Neurites / Q000187:drug effects; D016900:Neurofilament Proteins / Q000378:metabolism; D009924:Organ Culture Techniques; D051381:Rats; D009418:S100 Proteins / Q000378:metabolism; D012583:Schwann Cells / Q000187:drug effects; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000633:toxicity*
D000888:Antibodies, Anti-Idiotypic; D005732:Gangliosides; D004676:Myelin Basic Protein; D016900:Neurofilament Proteins; D009418:S100 Proteins; D014409:Tumor Necrosis Factor-alpha; C055253:IV(4)-galactosyl-N-acetylganglioside GD1a