Strongly enhanced toxicity of the mushroom toxin alpha-amanitin by an amatoxin-specific Fab or monoclonal antibody.
A monoclonal antibody, with high affinity against the mushroom toxin alpha-amanitin, was prepared. Administration of the Fab fragment of the monoclonal antibody to mice caused a 50-fold increase in alpha-amanitin toxicity. Electron micrographs showed normal appearance of hepatocytes but typical, amanitin-induced lesions in cells of the proximal convoluted tubules of the kidney. The pronounced nephrotoxicity is mainly explained by glomerular filtration and tubular reabsorption of the Fab-amatoxin complex and, to a lesser extent, of the immunoglobulin-amatoxin complex, which is still c. Twice as toxic as free alpha-amanitin. To our knowledge this is the first reported case where immunoglobulins or their fragments enhance rather than decrease the activity of a toxin. Accordingly, immunotherapy of Amanita mushroom poisoning in humans does not appear promising.
Faulstich
H
H
Max-Planck-Institut für Medizinische Forschung, Heidelberg, F.R.G.
Kirchner
K
K
Derenzini
M
M
D000546:Amanitins / Q000276:immunology / Q000627:therapeutic use / Q000633:toxicity*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology* / Q000627:therapeutic use; D007684:Kidney Tubules / Q000187:drug effects / Q000648:ultrastructure; D051379:Mice; D008815:Mice, Inbred Strains; D008854:Microscopy, Electron; D009145:Mushroom Poisoning / Q000628:therapy
D000546:Amanitins; D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; C049197:beta-amanitin; C018097:2-methyl-demethyl gamma-amanitin; C018207:amatoxin