The ABO blood group system is a classic example of agglutinogens and their corresponding isoantibodies. There are three of these antigens—A, B, and O—whose genes are placed in one locus on each of two paired chromosomes. These genes are alleles, meaning that they are interchangeable at their chromosome location. Therefore, each of the paired chromosomes carries any one of the three antigen genes. A and B are relatively strong antigens and serologically behave like dominant genes, whereas O is not detected by commercial typing sera and therefore the O antigen behaves serologically like a recessive gene. Blood group O is diagnosed by absence of reaction for either A or B antigen, so that O blood type implies O antigen on both chromosomes rather than only one. This makes four major phenotype groups possible—A, B, AB, and O—since A and B are dominant over O. Furthermore, when either A or B antigen is present on anindividual’s RBCs, the corresponding isoantibodies anti-A or anti-B will be absent from his or her serum; conversely, if an individual lacks either A or B antigen, his or her serum will contain the isoantibody to the missing isoantigen. O is so weak an antigen that for practical purposes it is considered nonantigenic. Therefore, a person who is AA or AO will have anti-B isoantibodies in his or her serum, a person who is OO will have both anti-A and anti-B isoantibodies, and so on. Why the body is stimulated to produce antibodies to the missing A or B antigens is not completely understood, but apparently antigens similar to ABO substances exist elsewhere in nature and somehow cause a natural sensitization. Anti-A and Anti-B are not detectable at birth, are weakly detectable at age 3-6 months, and gain maximum strength at age 5 years. Anti-A or anti-B incord blood or neonatal serum is usually of maternal origin.
Anti-A and anti-B are bivalent antibodies that react in saline at room temperature. Ordinarily, little difficulty is encountered in ABO typing. However, newborn A and B antigens may be weak and may not reach full strength until age 2-4 years, presenting the potential for false negative reaction in the newborn. There is a more common potentially serious situation that arises from the fact that subgroups of agglutinogen A exist. These are called A1, A2, and A3. The most common and strongest of these is A1, which comprises about 80% of group A and AB red cells, with A2 cells comprising most of the remaining 20% of red cells. A2 is troublesome because it is sometimes so weak that some commercial anti-A serums failto detect it. This may cause A2B to be falsely typed as B or A2O to be falsely typed as O. This situation is more likely to occur with polyclonal antibody typing sera and is not frequent with present-day potent blended monoclonal antibody typing sera (2 of 7124 patients in one study). Group A subgroups weaker than A2 exist but are rare. They are easily missed, even with potent anti-A typing serums. The main importance of the A2 subgroup is that persons with A2 sometimes have antibodies to A1 (the most common subgroup of A).
Anti-A1 is said to occur on 1%-8% of A2 persons and 22%-35% of A2B persons. These antibodies are usually not clinically important but may occasionally produce blood bank typing problems.
Group O serum contains an antibody (anti-A1B) that reacts against group A and group B cells more strongly than separate antibodies against group Aor group B cells. Serum from group O persons with high titer of anti-A1B was used to make an antiserum that can detect weak subgroups of A or B. Blended monoclonal A-B antibody is now available that produces even stronger reactions than the naturally occurring antibody.