ABO Blood Group System

          The ABO blood group system was the first system described and remains the most significant used for transfusion medicine. A mismatch of ABO may be fatal, whereas a mismatch of other blood groups initially is harmless. This situation occurs because anti-A and anti-B usually are present in the blood of adults lacking the corresponding antigen. These antibodies are stimulated by the ubiquitous distribution of the antigen that forms part of the membrane structure of many bacteria, plants, and animals. For this reason, all donor blood for transfusion is tested and labeled with the ABO group. The four main phenotypes are A, B, AB, and O, the latter indicating a lack of both A and B antigens. The sugars defining A and B antigens are added to carbohydrate chains carrying the H antigen (fucose), which is "hidden" by the A or B sugar. Thus group A or B erythrocytes appear to have less H antigen than group O cells. Nonetheless, H is found on all human erythrocytes except those in rare individuals of the O_h (Bombay) phenotype.

       Anti-A or anti-B can cause intravascular hemolysis when ABO-incompatible RBCs are transfused. Because A and B antigens also are expressed on most tissue cells, ABO compatibility is a significant consideration in solid organ transplantation. However, ABO incompatibility only rarely causes clinical HDN because antibodies directed against A and B antigens are predominantly immunoglobulin (Ig)M, which do not cross the placenta, and because A and B antigens are not fully developed on RBCs from a fetus.

       Although the ABO blood group system has only four phenotypes, more than 90 alleles have been identified by DNA analyses. The ABO gene was cloned in 1990 following purification of A transferase.^17,18 A and B transferase have only four amino acid differences in the catalytic domain, two of which (Leu266Met and Gly268Ala) are primarily responsible for substrate specificity.¹⁹ The group O phenotype results from mutations in A or B alleles that cause loss of glycosyltransferase activity. The most common group O (O₁) results from a single nucleotide deletion near the 5' end of the gene that causes a frameshift and early termination with no active enzyme production.²⁰ The ABO gene has seven exons, and A or B subgroups (with only few exceptions) result from a variety of mutations in exon 7 that cause alterations in the catalytic domain of the glycosyltransferase (reviewed by Chester and Olsson²¹). The rare B(A), A(B), and cis-AB phenotypes expressing both A and B antigens result from variant glycosyltransferases that have a combination of A- and B-specific residues.^22,23 Numerous common and rare ABO alleles have been reported, and current information is available on the blood group antigen gene mutation database web site (http://www.aecom.yu.edu). In addition to single point mutations, recombinations and gene rearrangements can result in hybrids with unexpected activity of the transferase. This situation makes typing of ABO by DNA analysis difficult to interpret.²⁴ The function of the ABO system is not known, although several disease associations are well established.