ABO blood group system

The ABO blood group system is used to denote the presence of one, both, or neither of the A and B antigens on erythrocytes. For human blood transfusions, it is the most important of the 48 different blood type classification systems currently recognized by the International Society of Blood Transfusions as of
June 2025. A mismatch in this serotype can cause a potentially fatal adverse reaction after a transfusion, or an unwanted immune response to an organ transplant. Such mismatches are rare in modern medicine. The associated anti-A and anti-B antibodies are usually IgM antibodies, produced in the first years of life by sensitization to environmental substances such as food, bacteria, and viruses.
The ABO blood types were discovered by Karl Landsteiner in 1901; he received the Nobel Prize in Physiology or Medicine in 1930 for this discovery. ABO blood types are also present in other primates such as apes, monkeys and Old World monkeys.

History

Discovery

The ABO blood types were first discovered by an Austrian physician, Karl Landsteiner, working at the Pathological-Anatomical Institute of the University of Vienna. In 1900, he found that red blood cells would clump together when mixed in test tubes with sera from different persons, and that some human blood also agglutinated with animal blood. He wrote a two-sentence footnote:
This was the first evidence that blood variations exist in humans — it was believed that all humans have similar blood. The next year, in 1901, he made a definitive observation that blood serum of an individual would agglutinate with only those of certain individuals. Based on this he classified human blood into three groups, namely group A, group B, and group C. He defined that group A blood agglutinates with group B, but never with its own type. Similarly, group B blood agglutinates with group A. Group C blood is different in that it agglutinates with both A and B.
This was the discovery of blood groups for which Landsteiner was awarded the Nobel Prize in Physiology or Medicine in 1930. In his paper, he referred to the specific blood group interactions as isoagglutination, and also introduced the concept of agglutinins, which is the actual basis of antigen-antibody reaction in the ABO system. He asserted:
Thus, he discovered two antigens and two antibodies. His third group indicated absence of both A and B antigens, but contains anti-A and anti-B. The following year, his students Adriano Sturli and Alfred von Decastello discovered the fourth type.
In 1910, Ludwik Hirszfeld and Emil Freiherr von Dungern introduced the term 0 for the group Landsteiner designated as C, and AB for the type discovered by Sturli and von Decastello. They were also the first to explain the genetic inheritance of the blood groups.

Classification systems

Czech serologist Jan Janský independently introduced blood type classification in 1907 in a local journal. He used the Roman numerical I, II, III, and IV. Unknown to Janský, an American physician William L. Moss devised a slightly different classification using the same numerical; his I, II, III, and IV corresponding to modern AB, A, B, and O.
These two systems created confusion and potential danger in medical practice. Moss's system was adopted in Britain, France, and US, while Janský's was preferred in most European countries and some parts of US. To resolve the chaos, the American Association of Immunologists, the Society of American Bacteriologists, and the Association of Pathologists and Bacteriologists made a joint recommendation in 1921 that the Jansky classification be adopted based on priority. But it was not followed particularly where Moss's system had been used.
In 1927, Landsteiner had moved to the Rockefeller Institute for Medical Research in New York. As a member of a committee of the National Research Council concerned with blood grouping, he suggested to substitute Janský's and Moss's systems with the letters O, A, B, and AB. This classification was adopted by the National Research Council and became variously known as the National Research Council classification, the International classification, and most popularly the "new" Landsteiner classification. The new system was gradually accepted and by the early 1950s, it was universally followed.

Other developments

The first practical use of blood typing in transfusion was by an American physician Reuben Ottenberg in 1907. Large-scale application began during the First World War when citric acid began to be used for blood clot prevention. Felix Bernstein demonstrated the correct blood group inheritance pattern of multiple alleles at one locus in 1924. Watkins and Morgan, in England, discovered that the ABO epitopes were conferred by sugars, to be specific, N-acetylgalactosamine for the A-type and galactose for the B-type. After much published literature claiming that the ABH substances were all attached to glycosphingolipids, Finne et al. found that the human erythrocyte glycoproteins contain polylactosamine chains that contains ABH substances attached and represent the majority of the antigens. The main glycoproteins carrying the ABH antigens were identified to be the Band 3 and Band 4.5 proteins and glycophorin. Later, Yamamoto's group showed the precise glycosyl transferase set that confers the A, B and O epitopes.

Genetics

Blood groups are inherited from both parents. The ABO blood type is controlled by a single gene with three types of alleles inferred from classical genetics: i, I^A, and I^B. The I designation stands for isoagglutinogen, another term for antigen. The gene encodes a glycosyltransferase—that is, an enzyme that modifies the carbohydrate content of the red blood cell antigens. The gene is located on the long arm of the ninth chromosome.
The I^A allele gives type A, I^B gives type B, and i gives type O. As both I^A and I^B are dominant over i, only ii people have type O blood. Individuals with I^AI^A or I^Ai have type A blood, and individuals with I^BI^B or I^Bi have type B. I^AI^B people have both phenotypes, because A and B express a special dominance relationship: codominance, which means that type A and B parents can have an AB child. A couple with type A and type B can also have a type O child if they are both heterozygous. The cis-AB phenotype has a single enzyme that creates both A and B antigens. The resulting red blood cells do not usually express A or B antigen at the same level that would be expected on common group A₁ or B red blood cells, which can help solve the problem of an apparently genetically impossible blood group.
Individuals with the rare Bombay phenotype produce antibodies against the A, B, and O groups and can only receive transfusions from other hh individuals. The table above summarizes the various blood groups that children may inherit from their parents. Genotypes are shown in the second column and in small print for the offspring: AO and AA both test as type A; BO and BB test as type B. The four possibilities represent the combinations obtained when one allele is taken from each parent; each has a 25% chance, but some occur more than once. The text above them summarizes the outcomes.
Historically, ABO blood tests were used in paternity testing, but in 1957 only 50% of American men falsely accused were able to use them as evidence against paternity. Occasionally, the blood types of children are not consistent with expectations—for example, a type O child can be born to an AB parent—due to rare situations, such as Bombay phenotype and cis AB.

Subgroups

The A blood type contains about 20 subgroups, of which A1 and A2 are the most common. A1 makes up about 80% of all A-type blood, with A2 making up almost all of the rest. These two subgroups are not always interchangeable as far as transfusion is concerned, as some A2 individuals produce antibodies against the A1 antigen. Complications can sometimes arise in rare cases when typing the blood.
With the development of DNA sequencing, it has been possible to identify a much larger number of alleles at the ABO locus, each of which can be categorized as A, B, or O in terms of the reaction to transfusion, but which can be distinguished by variations in the DNA sequence. There are six common alleles in white individuals of the ABO gene that produce one's blood type:

A	B	O
A101 A201	B101	O01 O02 O03

The same study also identified 18 rare alleles, which generally have a weaker glycosylation activity. People with weak alleles of A can sometimes express anti-A antibodies, though these are usually not clinically significant as they do not stably interact with the antigen at body temperature.
Cis AB is another rare variant, in which A and B antigens are transmitted together from a single parent.

Distribution and evolutionary history

The distribution of the blood groups A, B, O and AB varies across the world according to the population. There are also variations in blood type distribution within human subpopulations.
In the UK, the distribution of blood type frequencies through the population still shows some correlation to the distribution of placenames and to the successive invasions and migrations including Celts, Norsemen, Danes, Anglo-Saxons, and Normans who contributed the morphemes to the placenames and the genes to the population. The native Celts tended to have more type O blood, while the other populations tended to have more type A.
The two common O alleles, O01 and O02, share their first 261 nucleotides with the group A allele A01. However, unlike the group A allele, a guanosine base is subsequently deleted. A premature stop codon results from this frame-shift mutation. This variant is found worldwide, and likely predates human migration from Africa. The O01 allele is considered to predate the O02 allele.
Some evolutionary biologists theorize that there are four main lineages of the ABO gene and that mutations creating type O have occurred at least three times in humans. From oldest to youngest, these lineages comprise the following alleles: A101/A201/O09, B101, O02 and O01. The continued presence of the O alleles is hypothesized to be the result of balancing selection. Both theories contradict the previously held theory that type O blood evolved first.