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Abstract:
H. Faulstich, K. Kirchiner and M. Derenzini. Strongly enhanced toxicity of the mushroom toxin α-amanitin by an amatoxin-specific Fab or monoclonal antibody. Toxicon26, 491–499, 1988. — A monoclonal antibody, with high affinity against the mushroom toxin α-amanitin, was prepared. Administration of the Fab fragment of the monoclonal antibody to mice caused a 50-fold increase in α-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 α-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.
