Blood Type

The second most important blood group in humans is the Rhesus (Rh) system. Landsteiner and Wiener discovered the Rh blood group in 1940. They found that when they injected rabbits with Rhesus monkey blood; the rabbits produced antibodies against the Rhesus red cells. These antibodies reacted with red blood cells taken from 85 percent of Caucasians in New York City, who were thus said to be Rh positive, while the remaining 15 percent were Rh negative.

One year earlier (1939), Levine and Stetson published a paper describing the mother of a stillborn infant who had a severe reaction when transfused with her husband's blood. They tested the woman's serum and found that it reacted with 77 percent of blood donors. They postulated that the mother had been exposed to blood from her fetus and produced an antibody that reacted with it. The same antigen was present in the baby's father, explaining the woman's reaction to his blood. Their conclusion Incompatability in Rh type can cause hemolytic anemia in a second child. was correct, and later they realized that they had discovered the same antigen (Rh) that was discovered in the following year. The antibody found in the mother of the stillborn child was shown to be identical to the anti-Rh antibody produced in the rabbit by Landsteiner and Wiener.

The Rh blood group system is the major cause of hemolytic anemia in the newborn. A fetus who is Rh⁺ and whose mother is Rh⁻ is at high risk for this disorder, because the mother will produce antibodies against the fetal antigen. The first such fetus is usually not at risk since the fetal cells do not enter the mother's circulation until the time of birth. Only at this time does the mother produce anti-Rh⁺ antibodies. This complicates future pregnancies, because her antibodies will enter the fetal circulation system and react with fetal blood, causing hemolysis.

A treatment for Rh⁻ women at risk to have an Rh⁺ fetus is now widely used. Anti-Rh⁺ antibody is injected into the mother soon after her first delivery. This antibody coats the fetal Rh⁺ cells in the mother's circulation, which prevents them from causing antibody production in the mother and, therefore, her next child will not be at risk for hemolytic anemia.

The precise genetics of the complex Rh system has been in dispute since the early discoveries. The Rh blood group system is, in fact, much more complex than simply Rh⁺ and Rh⁻. There are two genes, one of which has four possible alleles, giving six antigens of which five are commonly tested. The first is D, which is the dominant gene that determines whether one is Rh⁺ or Rh⁻. Individuals with genotypes DD and Dd are Rh⁺ and those who are dd are Rh⁻. The DD and Dd genotypes cannot be distinguished from one another, since there is no "anti-d" antibody. The remaining four antigens are C, c, E, and e. The Rh locus is on the short arm of chromosome 1 and consists of two tandem genes. The first, RHCE, codes for non-RhD proteins while the second codes for the RhD protein. The Rh polypeptide has been sequenced. It contains 417 amino acids. Thus the molecular genetics conferring different antigenic Rh types is now clear.