BCH201 General Biochemistry

Topic Blood Group substances

Lecturer:

Learning Objectives: At the end of the class, students should be able to

 Name the types of blood group systems available

 Explain the ABO blood group
 Describe the Rhesus (Rh) blood group system
 Describe the H blood group system

A blood type (also called a blood group) is a classification of blood based on the
presence or absence of inherited antigenic substances on the surface of red blood
cells (RBCs). In the early 20th century, Karl Landsteiner, an Austrian scientist,
observed the surface of the RBCs and found two distinct chemical molecules. A
series of tests reported by Karl Landsteiner in 1900 led to the discovery of the ABO
blood groups and the development of routine blood grouping procedures. ABO
remains the most significant for transfusion practice. It is the only system in which
the reciprocal (or antithetical) antibodies (see Table 1) are consistently and
predictably present in the sera of normal people who have had no exposure to
human RBCs. Because of these antibodies, transfusion of ABO-incompatible blood
may cause severe intravascular haemolysis as well as the other manifestations of an
acute haemolytic transfusion reaction.

Table 1. Interpretation of ABO groups

Group Anti-A Anti-B A cells B cells

A + 0 0 +

B 0 + + 0

O 0 0 + +

AB + + 0 0

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ABO blood group system

Antigens of the ABO system

Red blood cell antigens may be proteins, carbohydrates, glycoproteins or

glycolipids, depending on the blood group system; some of these antigens are also
present on the surface of other types of cells of various tissues. Several of these
RBC surface antigens that stem from one allele (or very closely linked genes),
collectively form a blood group system

Three common alleles (A, B and O) are located at the ABO locus on chromosome
9. The A and B genes encode glycosyltransferases that produce the A and B
antigens, respectively. The O gene is considered to be non-functional, because its
protein product determines no detectable blood group antigen. The RBCs of group O
persons lack A and B, but carry an abundant amount of H antigen, the precursor
material on which A and B antigens are built.

Direct agglutination tests are used to detect A and B antigens on RBCs. Reagent
antibodies frequently produce weaker reactions with RBCs from new-borns than with
RBCs from adults. Although they can be detected on the RBCs of 5–6-week-old
embryos, A and B antigens are not fully developed at birth, presumably because the
branching oligosaccharide structures develop gradually. By the time a person is 2–4
years old, A and B antigen expression is fully developed, and remains fairly constant
throughout life.

Antibodies of the ABO system

Anti-A and anti-B, the common immunoglobulin M (IgM) antibodies to the RBC
surface antigens of the ABO blood group system, are sometimes described as being
‘naturally occurring’; however, this is a misnomer, because these antibodies are
formed in infancy by sensitization in the same way as other antibodies.

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The theory that explains how these antibodies are developed states that antigens
similar to the A and B antigens occur in nature, including in food, plants and bacteria.
After birth an infant gut becomes colonized with normal flora that expresses these A-
like and B-like antigens, causing the immune system to make antibodies to those
antigens that the RBCs do not possess. Therefore, people who are blood type A will
have anti-B, blood type B will have anti-A, blood type O will have both anti-A and
anti-B, and blood type AB will have neither. Because of these so called ‘naturally
occurring’ and expected antibodies, it is important to correctly determine a patient's
blood type prior to transfusion of any blood component. These naturally occurring
antibodies are of the IgM class, which have the capability of agglutinating (clumping)
and damaging RBCs within the blood vessels, possibly leading to death. It is not
necessary to determine any other blood groups, because almost all other RBC
antibodies can only develop through active immunization, which can only
occur through either previous blood transfusion or pregnancy. A test called the
antibody screen is always performed on patients who may require RBC transfusion,
and this test will detect most clinically significant RBC antibodies.

Rh blood group system

The Rh system is the second most significant blood group system in human blood
transfusion. There are five major antigens within the Rh blood group system: D, C,
E, c and e.

The most significant Rh antigen is the RhD antigen, because it is the most
immunogenic of the five main Rh antigens. It is common for RhD-negative
individuals not to have any anti-RhD IgG or IgM antibodies, because anti-RhD
antibodies are not usually produced by sensitization against environmental
substances. However, RhD-negative individuals can produce IgG anti-RhD
antibodies following a sensitizing event: possibly a fetomaternal transfusion of
blood from a fetus in pregnancy or occasionally a blood transfusion with RhD-
positive RBCs.

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Discovery of RhD antigen

The first human example of the antibody against the D antigen was reported in 1939
by Levine and Stetson, who found it in the serum of a woman whose fetus had
haemolytic disease of the newborn and who experienced a haemolytic reaction after
transfusion of her husband's blood. In 1940, Landsteiner and Wiener described an
antibody obtained by immunizing guinea pigs and rabbits with the RBCs of Rhesus
monkeys; it agglutinated the RBCs of approximately 85% of humans tested, and they
called the corresponding determinant the Rh factor. In the same year, Levine and
Katzin found similar antibodies in the serum of several recently delivered women,
and at least one of these sera gave reactions that paralleled those of the animal anti-
Rhesus sera. Also in 1940, Wiener and Peters observed antibodies of the same
specificity in the serum of persons whose RBCs lacked the determinant, who had
received ABO-compatible transfusions in the past. Later evidence established that
the antigen detected by animal anti-Rhesus and human anti-D were not identical, but
by that time the Rh blood group system had already received its name.

The H system

The H system has two genes, H and h, and one antigen, H, which serves as the
precursor molecule on which A and B antigens are built. On group O RBCs, there is
no A or B, and the membrane expresses abundant H. Individuals of the rare Oh
phenotype, whose RBCs lack H, have anti-A and anti-B, and a potent and clinically
significant anti-H in their serum. The term ‘Bombay’ has been used for the phenotype
in which RBCs lack H, A and B, because examples of such RBCs were first
discovered in Bombay, India. The Oh phenotype becomes apparent when serum
from the Oh individual is tested against group O RBCs, and strong, immediate
reactions occur.

Other blood group systems

The International Society of Blood Transfusion currently recognizes 30 blood group

systems (including the ABO ISBT No: 001 and Rh systems ISBT No: 004). Thus, in

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addition to the ABO antigens and Rh antigens, many other antigens are expressed
on the RBC surface membrane. A complete blood type would describe a full set of
30 substances on the surface of RBCs, and an individual's blood type is one of the
many possible combinations of blood group antigens. Across the 30 blood groups,
over 600 different blood group antigens have been found, but many of these are very
rare or are mainly found in certain ethnic groups. Almost always, an individual has
the same blood group for life; but very rarely an individual's blood type changes
through addition or suppression of an antigen in infection, malignancy or
autoimmune disease.