ABO blood groups and natural antibodies

DIAMED'S VIEW Structure of antigens

Structure

The ABO blood groups are different because distinct glycosyltransferases add N-acetylgalactosamine (antigen A) or galactose (antigen B) terminal sugars to precursor molecules (Biosythesis and heritance of AB and H antigens) . Numerous variants are described that belong to 4 main groups: among Europeans, about 3% have both A and B antigens (group AB), 45% have A (A), 9% have B (B) and 43% have neither A nor B (O).

Natural antibodies react against A and B antigens

Everybody has natural antibodies in the serum specific for the A or B antigens that are not expressed by the same individual. Natural antibodies against AB blood groups were discovered in 1901 by Landsteiner, who observed that when the blood of certain of his laboratory staff members was mixed together, the red blood cells would sometimes agglutinate and sometimes not, so that a blood transfusion would no longer be effective. These antibodies correspond to antigen from bacteria and other environmental agents (vegetables, meat, ...) and cross-react with the A and B blood groups presenting similarities in the glucidic chains.

These are so called “natural antibodies” because they are produced out of a pregnancy or transfusion context. They originate from the adaptive immune system, but, like the defenses of the innate, natural immune system, they are always ready to function in that they can cross-react with novel pathogens. Anti-AB antibodies are mainly IgM. Many other natural antibodies occur; all humans reject vascularized xenografts from pigs. Regarding blood transfusion, hyperacute rejection means intravascular hemolysis by complement; IgM strongly activates the classical complement pathway, up to the formation of the membrane attack complex. The clinical condition is severe: shock, anuria, high mortality.

Transfusion rules

Since the A and B antigens also occur on bacteria of the commensal intestinal flora, every person with a normal immune system has circulating antibodies reacting with those sugars which are not present on own cells. This is a convincing demonstration of self-tolerance: group O produce anti-A and anti-B antibodies and thus tolerate only O cells (plasma is dangerous, but group O is considered as "universal donor" of erythrocyte concentrates).

Group AB, tolerant for A and B antigens, produce neither anti-A nor anti-B antibodies and thus accept AB, A, B or O cells (plasma AB is welcomed by all other groups, but red cells are rejected by all other groups).

Platelet transfusions, if possible, should also be ABO compatible regarding plasma blood group. If the platelets react with the recipient’s antibodies their half-life is shortened.