Specificity of xenoreactive anti-Gal alpha 1-3Gal IgM for alpha-galactosyl ligands

The transplantation of organs from lower animals such as pigs into humans is prevented by a severe rejection reaction initiated by complement fixing xenoreactive natural antibodies. Most anti-pig xenoreactive natural antibodies in humans are thought to recognize Gal alpha 1-3Gal beta 1-4GlcNAc and are also thought to recognize, albeit less avidly, Gal alpha 1-6Glc. Gal alpha 1-6Glc has been used as a ligand for purification of 'anti-Gal alpha 1-3Gal antibodies' and as a therapeutic or reagent to prevent the binding of these antibodies to porcine organs or cells, We tested the specificity of anti-Gal alpha 1-3Gal IgM for Gal alpha 1-6Glc and related saccharides. Based on inhibition of binding of xenoreactive anti-Gal alpha 1-3Gal IgM to porcine cells by soluble saccharides, anti-Gal alpha 1-3Gal IgM in a human serum was found to consist of a mixture of antibodies which have a similar affinity for Gal alpha 1-3Gal but varying affinities for Gal alpha l-6Glc and other structures, Twenty to 40% of the anti-Galal-3Gal IgM from the population tested did not recognize Gal alpha 1-6Glc. The binding of anti-Gal alpha 1-3Gal IgM to Gal alpha 1-6Glc varied widely from individual to individual, some samples lacking almost entirely anti-Gal alpha 1-3Gal IgM which bound to Gal alpha 1-6Glc.