In vitro induction of neuronal apoptosis by anti-Fas antibody-containing sera from amyotrophic lateral sclerosis patients.
Sera from 26% of patients with sporadic amyotrophic lateral sclerosis (ALS) induced in vitro apoptosis of a human neuroblastoma cell line, as detected by two methods, and most contained anti-Fas autoantibodies. In contrast, Alzheimer sera (studied as controls) very rarely induced apoptosis and did not contain detectable anti-Fas antibodies. Soluble Fas-ligand levels in ALS sera were not different from those in normal sera, except for slightly higher levels in a single case. In mixed cultures of rat embryonic brain and spinal cord cells, ALS sera (and agonistic anti-Fas monoclonal antibodies and soluble Fas-ligand) induced the apoptosis of a subpopulation of neurons. These neurons were motoneurons on the basis of staining with the monoclonal antibody SMI 32 and Fas expression was restricted to these SMI 32-positive neurons. These data are compatible with the hypothesis of the participation of an autoimmune mechanism possibly related to anti-Fas autoantibodies in certain ALS patients.
Yi
F H
FH
Laboratory of Immunology, University Hospital, 2 avenue Martin Luther King, CNRS EP 118, 87042 Cedex, Limoges, France.
Lautrette
C
C
Vermot-Desroches
C
C
Bordessoule
D
D
Couratier
P
P
Wijdenes
J
J
Preud'homme
J L
JL
Jauberteau
M O
MO
D000690:Amyotrophic Lateral Sclerosis / Q000276:immunology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D001323:Autoantibodies / Q000032:analysis / Q000494:pharmacology; D015153:Blotting, Western; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D061945:Caspase Inhibitors; D002490:Central Nervous System / Q000166:cytology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007106:Immune Sera / Q000494:pharmacology; D020287:In Situ Nick-End Labeling; D066298:In Vitro Techniques; D019169:Jurkat Cells; D008297:Male; D008875:Middle Aged; D009046:Motor Neurons / Q000166:cytology* / Q000276:immunology*; D009447:Neuroblastoma; D051381:Rats; D011994:Recombinant Proteins / Q000276:immunology; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000276:immunology*
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D007106:Immune Sera; D011994:Recombinant Proteins; D019014:fas Receptor; C505407:CASP3 protein, human; C505530:CASP8 protein, human; C506433:CASP9 protein, human; C505410:Casp3 protein, rat; C505528:Casp8 protein, rat; C506435:Casp9 protein, rat; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9