Antigen Expression - Variation in Antigen Expression

        RBCs from individuals who are homozygous for an allele typically have a greater number of antigen sites than do individuals who are heterozygous. Consequently, their RBCs can react more strongly with antibody. This difference in expression and antigen–antibody reactivity because of zygosity is known as dosage. For example, RBCs from a homozygous MM individual carry a double dose of M antigen and react more strongly with anti-M than do RBCs from a MN heterozygous individual carrying only a single dose of M. Antithetical antigens C/c, E/e, M/N, S/s, and Jk^a/Jk^b commonly show dosage. Dosage is less obvious with D, K/k, and Lu^a/Lu^b antigens. It typically is more apparent within a family than between families. Dosage within the Duffy system also may not be serologically obvious because Fy(a+b–) or Fy(a–b+) phenotypes are seen in either homozygous (Fy^aFy^a or Fy^bFy^b) or heterozygous (Fy^aFy or Fy^bFy) individuals.

Antigen Expression - Antigen Development on Fetal Erythrocytes

         Most RBC antigens can be detected early in fetal development (A, B, and H antigens can be detected at 5–6 weeks' gestation), but not all are fully developed at birth. A, B, H, I, P1, Lu^a, Lu^b, Yt^a, Xg^a, Vel, Bg, Knops, and Dombrock antigen expression is considerably weaker on cord erythrocytes than on RBCs from adults. Le^a, sometimes Le^b, Ch/Rg, AnWj, and Sd^a, are not readily detectable, although 50 percent of cord samples type Le(a+) with more sensitive test methods. Full expression of A, B, H, I, and Lewis antigens usually is present by age 3 years, whereas full expression of P1 and Lutheran antigens may not occur until age 7 years.

Other Blood Group Systems

          In terms of transfusion and HDN, the other blood group systems and their antigens become important only when antibody develops. Transfusion service laboratories identify (antibody identification) the specificity and characterize the reactivity of antibodies detected in routine testing (antibody screening). Once this information is known, the blood bank assesses the clinical significance of the antibody and selects the most appropriate blood for transfusion. A detailed description of all the blood group antigens is beyond the scope of this chapter. Because the molecular bases of most blood group antigens and phenotypes are known, DNA analysis can be used to type transfused patients and to identify the fetus at risk for HDN.

Rh Blood Group System

        The Rh (not Rhesus) system is the second most important blood group system in transfusion medicine because antigen-positive RBCs frequently immunize antigen-negative individuals through transfusion and pregnancy.

       Inheritance of Rh antigens is determined by a complex of two closely linked genes: one encodes the protein carrying D antigen (RhD); the other encodes the protein carrying C or c and E or e antigens (RhCE). RBCs from Rh-positive people have both RhD and RhCE, whereas Rh-negative RBCs have only RHCE. In the Rh system, eight common antigen combinations or haplotypes are possible: Dce (R₀, Rh₀), DCe (R₁, Rh₁), DcE (R_2, Rh₂), DCE (R_Z, Rh_z), ce (r, rh), Ce (r', hr'), cE (r″, hr″), and CE (ry, rh″). The letter "d" is commonly used to designate the lack of D, but there is no d antigen or anti-d.

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.