Blood Type

Blood has two main components: serum and cells. In 1900 Karl Landsteiner, a physician at the University of Vienna, Austria, noted that the sera of some individuals caused the red cells of others to agglutinate. This observation led to the discovery of the ABO blood group system, for which Landsteiner received the Nobel Prize. Based on the reactions between the red blood cells and the sera, he was able to divide individuals into three groups: A, B, and O. Two years later, two of his students discovered the fourth and rarest type, namely AB.

Antigens and Antibodies

To understand blood typing, it is necessary to define antigen and antibody. An antigen is a substance, usually a protein or a glycoprotein, which, when injected into a human (or other organism) that does not have the antigen,

RELATIONSHIPS BETWEEN BLOOD TYPES AND ANTIBODIES
Blood Type	Antigens on Red Blood Cell	Can Donate Blood To	Antibodies in Serum	Can Receive Blood From
A	A	A, AB	Anti-B	A, O
B	B	B, AB	Anti-A	B, O
AB	A and B	AB	None	AB, O
O	None	A, B, AB, O	Anti-A and anti-B	O

will cause an antibody to be produced. Antibodies are a specific type of immune-system proteins known as immunoglobulins, whose role is to fight infections by binding themselves to antigens. In the case of the ABO blood groups, the antigens are present on the surface of the red blood cell, while the antibodies are in the serum. These antibodies are unique to the ABO system and are termed "naturally occurring antibodies." The table shows the relationships between blood types and antibodies.

This aspect of the ABO blood group system is very important in transfusion. Blood group O individuals are said to be universal donors, because their blood can be used for transfusion in individuals who have any one of the four blood types. On the other hand, individuals with blood type A can only donate to either type A or type AB, and individuals with blood type B can only donate to B or AB types. AB individuals can only donate to type AB. However, before any transfusions, donor blood is mixed with serum from the recipient (a process called cross matching) to ensure that no agglutination will occur after transfusion.

Multiple Alleles

The genetic basis of the ABO blood group system is an example of multiple alleles. There are three alleles, A, B, and O, at the ABO locus on chromosome 9. The expression of the O allele is recessive to that of A and B, which are said to be co-dominant. Thus, the genotypes AO and AA express blood type A, BO and BB express blood type B, AB expresses blood type AB, and OO expresses blood type O. In the past, ABO blood group typing was used extensively both in forensic cases as well as for paternity testing. More recently, DNA testing, which is much more informative, has superseded these tests.

The ABO blood group substances are glycoproteins, the basic molecule of which is known as the H substance. This H substance is present in unmodified form in individuals with blood type O. Adding extra sugar molecules to the H substance produces the A and B substances. The frequency of the ABO blood types varies widely across the globe. For example, blood group B has a frequency of 25 percent in Asians, 17 percent in Africans, but only 8 percent in Caucasians. The frequency of blood group O in Europe increases as one travels from southern to northern countries.

Alleles at a locus independent of the ABO blood group locus, known as the secretor locus, determine an individual's ability to secrete the ABO blood group substances in saliva and other body fluids. There are two genes, Se and se, where Se is dominant to se. In other words, an individual with at least one Se gene is a secretor. Approximately 77 percent of Europeans are secretors. This frequency is rarely less than 50 percent and sometimes as high as 100 percent in other populations.

An interesting aspect of the ABO blood groups is their association with disease. Among individuals with stomach and peptic ulcers, there is an excess of type O individuals, whereas among those with cancer of the stomach, there is an excess of type A individuals. Not all type O individuals have an increased risk for peptic or stomach ulcers, however. If type O individuals are secretors, they are protected against ulceration, whereas non-secretors have a two-fold increased risk. Thus the presence of ABO blood group substances act as a protective agent against the development of stomach and peptic ulcers.

The Rh System

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 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.

P. Michael Conneally

Bibliography

Cavalli-Sforza, L. L., and W. F. Bodmer. The Genetics of Human Populations. San Francisco: W. H. Freeman and Company, 1971.

Huang, Cheng-Han, Philip Z. Liu, and Jeffrey G. Cheng. "Molecular Biology and Genetics of the Rh Blood Group System." Seminars in Hematology 37, no. 2 (2000): 150-165.

Race, R. R., and Ruth Sanger. Blood Groups in Man, 6th ed. Oxford, U.K.: Blackwell Scientific Publications, 1975.

Internet Resource

"Blood Types." Indiana State University. <http://www.indstate.edu/thcme/mwking/abo-bloodgroups.gif>.