A human antibody binds to alpha-galactose receptors and mimics the effects of Clostridium difficile toxin A in rat colon

Background & Aims: Nearly all human sera contain an immunoglobulin G antibody (antigalactose) that binds the trisaccharide Gal alpha 1-3Gal beta 1-4GlcNAc expressed on cells from most mammals but not humans, Because the Clostridium difficile toxin A receptor in rodents contains this trisaccharide, the aim of this study was to examine whether antigalactose could mimic the enterotoxic effects of toxin A and bind to receptors containing this trisaccharide. Methods: Fluid secretion, [H-3]-mannitol permeability, and release of rat mast cell protease Il and prostaglandin E(2) were measured after luminal exposure of rat colon to either purified human anti-galactose, control immunoglobulin G, toxin A, or buffer, Results: Toxin A (5 mu g) and antigalactose (250 mu g) but not control immunoglobulin (250 mu g) stimulated colonic fluid secretion and caused increased mannitol permeability and rat mast cell protease II release, Antigalactose and toxin A and, to a lesser degree, control immunoglobulin G also stimulated release of prostaglandin E(2), but only toxin A produced acute inflammation of rat colonic mucosa, Antigalactose and toxin A bound specifically to a single class of colonic brush border receptors with dissociation constants of 10(-6) mol/L and 5.4 x 18(-8) mol/L, respectively. Conclusions: Fluid secretion, increased permeability, and mast cell activation occur in rat colon when toxin A or human antigalactose immunoglobulin G bind to receptors bearing the trisaccharide Gal alpha 1-3Gal beta 1-4GlcNAc.