Blood Groups in Human

Introduction:

The human blood groups are usually defined by the antigens present on the surface of the erythrocytes. Specific alloantibodies serologically define these antigens. Blood groups were discovered by Karl Landsteiner at the beginning of the twentieth century when he noted that plasma from one individual agglutinates the RBCs from other. In 1945, Coombs, Mourant, and Race developed the technique of the antiglobulin test, which allowed the study of non-agglutinating antibodies. Since then, 349 blood group antigens have been identified by the International Society of Blood Transfusion (ISBT). The majority of these antigens belong to 43 blood groups. A gene or cluster of closely related genes controls the genetically discrete group of antigens. The number of antigens in the group determines the complexity of blood groups. Some of these blood groups (like Hh, Kx, Globoside) are simple and contain a single antigen; others are complex and contain about fifty antigens. MNS and Rh blood groups are the most complex, with 46 and 52 antigens, respectively. Some blood group antigens are synthesized by RBCs and present on their surface. Other antigens are found throughout the body. Biochemically, the blood antigens are of two kinds—first, the protein determinants, and second, the carbohydrate determinants.

The blood group system:

A blood group system consists of one or more antigens controlled by a single gene locus or two or more homologous genes. However, ABO and RH blood groups are most important for a blood transfusion, but some other blood antigens are known to cause hemolytic transfusion reactions or hemolytic disease in newborns. Some important blood groups are discussed below.

ABO Blood Group

In 1900, Landsteiner reported, ‘ The serum of healthy humans has an agglutinating effect on animal blood corpuscles and human blood corpuscles from different individuals.’ In the following year, he also recognized three blood types: A, B and C (later called O). Epstein and Ottenberg suggested that the blood groups are inherited. In 1910, Von Dungern and Hirschfeld confirmed that the A and B antigens inheritance obeyed Mendel’s laws. In 1924, Bernstein showed that only three alleles (IA, IB & IO) at one locus were necessary for its inheritance.

There is three alleles IA, IB & IO  located on chromosome 9, which produces three antigens, A, B and O, respectively. There are six possible combinations of these three alleles (genotypes). As the alleles, IA and IB are codominant to each other, and both are dominant over IO allele, only four blood types in this group are possible.

For the discovery of blood groups, Landsteiner received the Noble prize in 1930.

The table below represents the blood types of the ABO blood group, antigens present on the RBCs, antibodies present in the serum, and possible genotypes.

ABO blood type

Antigen on RBCs

Antibodies in serum

Genotypes

A (two sub-types)

A

Anti-B

IAIA, IAIO

B

B

Anti-A

IBIB, IBIO

AB

Both A and B

None

IAIB

O

None

Both anti-A and anti-B

IOIO

Although the alleles of the ABO gene are located on chromosome 9; chromosome 19 carries genes that produce H-antigen. The gene products (enzymes) of the ABO gene modify the H-antigen. The products of IA allele are a glycosyltransferase enzyme which adds a terminal N-acetylglucosamine to the H-substance on the RBC membrane producing antigen A. IB allele produces another glycosyltransferase enzyme which adds a terminal galactose to the H-substance producing antigen B. IO allele produces inactive transferase enzyme which is incapable of adding any sugar to the H-antigen and hence, it remains unaltered. The pathway for synthesis of A and B antigens from H-substance, the structure of these antigens, and their cartoon representation are as follows.

Synthesis pathway of antigens of ABO blood group
Schematic representation of A and B antigens, and H substance of ABO blood group
Cartoon of the A and B antigens of ABO blood group

Rh Blood Group and Rh incompatibility:

Investigation of a haemolytic blood transfusion reaction by Levine and Stetson in 1939 led to identifying Rh antigen. Rh stands for Rhesus, as the antigen was identified by alloantibody produced in rabbits by injecting RBCs of the Rhesus monkey. The Rh antigen is present in the RBCs of nearly 80% of the population. Later, it was found that the Rh-positive was inherited as a dominant character.

The Rh antigens (52 in number) are encoded by two homologous genes, RHD and RHCE, located on chromosome 1. RHD produces antigen D (RH1), often called Rh or rhesus antigen, and RHCE produces Cc and Ee antigens. The presence or absence of the D antigen produces two phenotypes, Rh-positive and Rh-negative respectively.

Rh incompatibility:

When a person with Rh-negative blood is exposed to Rh-positive blood, the Rh-negative person starts preparing antibodies against the Rh antigen. Hence, this blood group is also significant for blood transfusion.

Levine et al. confirmed that incompatibility between mother and foetus was the cause of erythroblastosis fetalis or haemolytic disease of the newborn (HDN). HDN is caused if the pregnant mother is Rh negative and the developing foetus is Rh positive. During childbirth, the accidental mixing of blood from a child with the mother’s blood causes anti-Rh antibodies in the mother’s blood. During the subsequent pregnancy, if the foetus is Rh positive, an anti-Rh antibody developed in the mother’s blood during the previous pregnancy leak into the foetal blood, causing loss of RBCs which leads to severe anaemia and jaundice or even death of the young one.

For Blood transfusion, ABO and Rh blood group is very significant. Hence, the blood types of these two groups are represented together. The (+) and the (-) signs with blood type represent Rh positive and negative, respectively.

Blood transfusion compatibility:

Blood Type

Can be transfused to

Can Receive From

A-Positive

A-Positive, AB-Positive

A-Positive, A-Negative,

O-Positive, O- Negative

A-Negative

A-Positive, A-Negative,

AB-Positive, AB-Negative

A-Negative, O- Negative

B-Positive

B-Positive, AB-Positive

B-Positive, B-Negative,

O-Positive, O- Negative

B-Negative

B-Positive, B-Negative,

AB-Positive, AB-Negative

B-Negative, O- Negative

AB-Positive

AB-Positive

ALL (Universal Acceptor)

AB-Negative

AB-Positive, AB-Negative

A-Negative, B-Negative,

AB-Negative, O- Negative

O-Positive

A-Positive, B-Positive,

AB-Positive, O-Positive

O-Positive, O- Negative

O-Negative

ALL (Universal Doner)

O- Negative

MNS Blood Group

MNS was the second blood group discovered. It was discovered by Landsteiner and Levine in 1927 when antibodies against M and N antigens were found. MN is polymorphic in all populations. M and N determinants are carried on glycophorin A (GPA). Sialic acid also plays a role in expressing M and N antigens. In 1947, another related S-antigen was found, expressing glycophorin B (GPB). MNS blood group system is clinically not significant.

The Bombay Phenotype

There are a few blood groups which contain only one antigen. One such group is Hh blood group. Hh blood group contains the antigen H. It is found on all RBCs and serves as the precursor of A and B antigen synthesis.

Because the H antigen (H substance) serves as a precursor of A and B antigens, the absence of the H antigen will lead to the absence of either of the antigens of the ABO blood group. In such cases, the individual carrying mutation for H antigen will not be able to form A or B antigen even if the genes for their production are present. Such individuals will have “O” type blood. It was discovered in Bombay, India, in 1952, and therefore, it was named the “Bombay phenotype“.  

Out of more than thirty blood groups discovered in humans, ABO and Rh blood groups are clinically significant. With the advancement of technology, more and more information is being gathered about human blood groups. It is helping us improve medical technologies to treat patients suffering from blood-related disorders.

References:

Daniels, G. (2013). Human Blood Groups: Daniels/human blood groups (3rd ed.). Wiley-Blackwell.

Storry, J. R., et al. “International Society of Blood Transfusion Working Party on red cell immunogenetics and blood group terminology: Cancun report (2012).” Vox sanguinis 107.1 (2014): 90-96.

Coombs, Robin Royston Amos, A. E. Mourant, and R. R. Race. “Detection of weak and “incomplete” Rh agglutinins: a new test.” Rhesus haemolytic disease. Springer, Dordrecht, 1945. 88-88.

Landsteiner K. Zur Kenntnis der antifermentativen, lytischen und agglutinietenden Wirkungen des Blutserums und der Lymphe. Zentralbl Bakt 1900;27: 357–66.

Landsteiner K. Über Agglutinationserscheinungen normalen menschlichen Blutes. Agglutination phenomena in normal human blood. Wien Klin Wochenschr 1901;14:1132–4.

Epstein AA, Ottenberg R. A simple method of performing serum reactions. Proc NY Path Soc 1908;8:117–23.

von Dungern E, Hirschfeld L. Ueber Vererbung gruppenspezifischer Strukturen des Blutes. Z Immun Forsch 1910;6:284–92. [For translation see Transfusion 1962;2:70–4.]

Bernstein F. Ergebnisse einer biostatistischen zusammenfassenden Betrachtung über die erblichen Blutstrukturen des Menschen. Klin Wochenschr 1924;3:1495–7.

Bernstein F. Zussammenfassende Betrachttungen über die erblichen Blutstrukturen des Menschen. Z Indukt Abstamm u VerebLehre 1925;37:237–70.

Blood Group Terminology | The International Society of Blood Transfusion (ISBT) (isbtweb.org)

https://www.sciencedirect.com/referencework/9780080961569/brenners-encyclopedia-of-genetics

Levine P, Burnham L, Katzin EM, Vogel P. The role of iso-immunization in the pathogenesis of erythroblastosis fetalis. Am J Obst Gynecol 1941;42:925–37.

Levine P, Katzin EM, Burnham L. Isoimmunization in pregnancy: its possible bearing on the etiology of erythroblastosis foetalis. J Am Med Assoc 1941;116: 825–7.

Levine P, Vogel P, Katzin EM, Burnham L. Pathogenesis of erythroblastosis fetalis: statistical evidence. Science 1941;94:371–2.

blood group A antigen type 1 | C28H48N2O20 – PubChem (nih.gov)

Blood Group Type V B-antigen | C24H42O20 – PubChem (nih.gov)

https://www.ncbi.nlm.nih.gov/books/NBK2268/

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