Isohemagglutinins and xenoreactive antibodies: members of a distinct family of natural antibodies.

Just as anti-blood group A and anti-blood group B antibodies pose a strong humoral barrier to the transplantation of allogeneic organs or blood, xenoreactive natural antibodies directed against Gal alpha 1-3Gal pose a barrier to the transplantation of xenogeneic organs or blood. We tested the idea that, although "natural" iso-hemagglutinins and xenoreactive natural antibodies recognize distinct structures, they have a similar origin and function. Anti-A antibodies, anti-B antibodies, and xenoreactive natural antibodies were present in serum at similar concentrations and varied with age, gender, and the concentration of total IgM in serum in a similar manner. Anti-A antibodies, anti-B antibodies, and xenoreactive natural antibodies, unlike some elicited antibodies, had a high degree of thermal lability and bound more avidly at lower temperatures. The natural antibodies manifest remarkable homogeneity and high functional avidity for determinants on a cell surface but only a weak affinity for monovalent ligands. These findings suggest that anti-A antibodies, anti-B antibodies, and xenoreactive natural antibodies specific for Gal alpha 1-3Gal have a common origin and function and, given similar antigen density on target cells, provide similar humoral barriers to transplantation or transfusion and that these antibodies may be members of a common "family" of antibodies.