ABO blood group system



The ABO blood group system is the most important blood type system (or blood group system) in human blood transfusion. The associated anti-A antibodies and anti-B antibodies are usually IgM antibodies, which are usually produced in the first years of life by sensitization to environmental substances such as food, bacteria, and viruses. ABO blood types are also present in some animals, for example apes such as chimpanzees, bonobos, and gorillas.

History of discoveries
The ABO blood group system is widely credited to have been discovered by the Austrian scientist Karl Landsteiner, who found three different blood types in 1900; he was awarded the Nobel Prize in Physiology or Medicine in 1930 for his work. Due to inadequate communication at the time it was subsequently found that Czech serologist Jan Janský had independently pioneered the classification of human blood into four groups, but Landsteiner's independent discovery had been accepted by the scientific world while Janský remained in relative obscurity. Janský's classification is however still used in Russia and states of former USSR (see below). In America, Moss published his own (very similar) work in 1910.

Landsteiner described A, B, and O; Alfred von Decastello and Adriano Sturli discovered the fourth type, AB, in 1902. Ludwik Hirszfeld and E. von Dungern discovered the heritability of ABO blood groups in 1910–11, with Felix Bernstein demonstrating 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, Laine's group (1988) found that the band 3 protein expressed a long polylactosamine chain that contains the major portion of the ABH substances attached. Later, Yamamoto's group showed the precise glycosyl transferase set that confers the A, B and O epitopes.

ABO antigens


The H antigen is an essential precursor to the ABO blood group antigens. The H locus is located on chromosome 19. It contains 3 exons that span more than 5 kb of genomic DNA, and it encodes a fucosyltransferase that produces the H antigen on RBCs. The H antigen is a carbohydrate sequence with carbohydrates linked mainly to protein (with a minor fraction attached to ceramide moiety). It consists of a chain of β-D-galactose, β-D-N-acetylglucosamine, β-D-galactose, and 2-linked, α-L-fucose, the chain being attached to the protein or ceramide.

The ABO locus is located on chromosome 9. It contains 7 exons that span more than 18 kb of genomic DNA. Exon 7 is the largest and contains most of the coding sequence. The ABO locus has three main alleleic forms: A, B, and O. The A allele encodes a glycosyltransferase that bonds α-N-acetylgalactosamine to D-galactose end of H antigen, producing the A antigen. The B allele encodes a glycosyltransferase that joins α-D-galactose bonded to D-galactose end of H antigen, creating the B antigen.

In case of O allele, the exon 6 contains a deletion that results in a loss of enzymatic activity. The O allele differs from the A allele by deletion of only one nucleotide – guanine at position 261. The deletion causes a frameshift, and results in premature termination of translation, and thus, degradation of the mRNA. This results in H antigen remaining unchanged in case of O groups.

The majority of the ABO antigens are expressed on the ends of long polylactosamine chains attached mainly to band 3 protein, the anion exchange protein of the RBC membrane, and a minority of the epitopes are expressed on neutral glycosphingolipids.

Serology
Anti-A and anti-B antibodies (called isohaemagglutinins), which are not present in the newborn, appear in the first years of life. They are isoantibodies, that is, they are produced by an individual against antigens produced by members of the same species (isoantigens). Anti-A and anti-B antibodies are usually IgM type, which are not able to pass through the placenta to the fetal blood circulation. O-type individuals can produce IgG-type ABO antibodies.

Origin theories
It is possible that food and environmental antigens (bacterial, viral, or plant antigens) have epitopes similar enough to A and B glycoprotein antigens. The antibodies created against these environmental antigens in the first years of life can cross-react with ABO-incompatible red blood cells that it comes in contact with during blood transfusion later in life. Anti-A antibodies are hypothesized to originate from immune response towards influenza virus, whose epitopes are similar enough to the α-D-N-galactosamine on the A glycoprotein to be able to elicit a cross-reaction. Anti-B antibodies are hypothesized to originate from antibodies produced against Gram-negative bacteria, such as E. coli, cross-reacting with the α-D-galactose on the B glycoprotein.

The "Light in the Dark theory" (DelNagro, 1998) suggests that, when budding viruses acquire host cell membranes from one human patient (in particular, from the lung and mucosal epithelium where they are highly expressed), they also take along ABO blood antigens from those membranes, and may carry them into secondary recipients where these antigens can elicit a host immune response against these non-self foreign blood antigens. These viral-carried human blood antigens may be responsible for priming newborns into producing neutralizing antibodies against foreign blood antigens. Support for this theory has come to light in recent experiments with HIV. HIV can be neutralized in in vitro experiments using antibodies against blood group antigens specifically expressed on the HIV-producing cell lines.

The "Light in the Dark theory" suggests a novel evolutionary hypothesis: there is true communal immunity, which has developed to reduce the inter-transmissibility of viruses within a population. It suggests that individuals in a population supply and make a diversity of unique antigenic moieties so as to keep the population as a whole more resistant to infection. A system set up ideally to work with variable recessive alleles.

However, it is more likely that the force driving evolution of allele diversity is simply negative frequency-dependent selection; cells with rare variants of membrane antigens are more easily distinguished by the immune system from pathogens carrying antigens from other hosts. Thus, individuals possessing rare types are better equipped to detect pathogens. The high within-population diversity observed in human populations would, then, be a consequence of natural selection on individuals

Nonantigen biology
The carbohydrate molecules on the surfaces of red blood cells have roles in cell membrane   integrity,  cell adhesion, membrane transportation of molecules, and acting as receptors for extracellular ligands, and enzymes. ABO antigens are found having similar roles on epithelial cells as well as red blood cells.

Transfusion reactions
Due to the presence of isoantibodies against non-self blood group antigens, individuals of type A blood group immediately raise anti-B antibodies against B-blood group RBCs if transfused with blood from B group. The anti-B antibodies bind to B antigens on RBCs and cause complement-mediated lysis of the RBCs. The same happens for B and O groups (which raises both anti-A and anti-B antibodies). However, only blood group AB does not have anti-A and anti-B isoantibodies. This is because both A and B-antigens are present on the RBCs and are both self-antigens, hence they can receive blood from all groups and are universal recipient.

As far as transfusion compatibility is concerned, it is not strictly as simple as matching A, B, and O groups. In other words, no individual will ever receive a blood transfusion based on the ABO system alone. The rhesus factor must also be considered. Together, the rhesus factor and ABO grouping are the two most important compatibility factors to consider. An individual may be Rh+ or Rh-. In simpler terms, if an individual is blood type A and positive for the rhesus factor, then he or she is deemed "A+".


 * * Type AB+ is the universal recipient: Although those with AB blood type may be referred to as universal recipients, in actuality, type AB+ blood is that of the universal recipient, whereas type AB- is not. This is an important distinction to make.


 * ** Because A-, A+, B-, B+, AB-, AB+, O- and O+ individuals can all receive blood from donors of type O- blood, an individual with type O- blood is deemed universal donor. In similar manner, O+ is not the universal donor blood type.

One caveat to this axiom of 'universal donor' is that this applies to packed RBCs, and not to whole blood products. Using the first table, type O carries anti-A and anti-B antibodies in the serum. To transfuse a type A, B, or AB recipient with type O whole blood would produce a hemolytic transfusion reaction due to the antibodies found in the serum of whole blood.

No antibodies are formed against the H antigen, except in those individuals with the Bombay phenotype.

In ABH secretors, ABH antigens are secreted by most mucus-producing cells of the body interfacing with the environment, including lung, skin, liver, pancreas, stomach, intestines, ovaries, and prostate.

ABO hemolytic disease of the newborn
ABO blood group incompatibilities between the mother and child does not usually cause hemolytic disease of the newborn (HDN) because antibodies to the ABO blood groups are usually of the IgM type, which do not cross the placenta; however, in an O-type mother, IgG ABO antibodies are produced and the baby can develop ABO hemolytic disease of the newborn.

Inheritance


Blood groups are inherited from both parents. The ABO blood type is controlled by a single gene (the ABO gene) with three alleles: i, IA, and IB. 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 (9q34).

The IA allele gives type A, IB gives type B, and i gives type O. As both IA and IB are dominant over i, only ii people have type O blood. Individuals with IAIA or IAi have type A blood, and individuals with IBIB or IBi have type B. IAIB 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 type A and a type B couple can also have a type O child if they are both heterozygous (IBi,IAi) 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.

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 Vikings, Danes, Saxons, Celts, and Normans who contributed the morphemes to the placenames and the genes to the population.

There are six common alleles in white individuals of the ABO gene that produce one's blood type:


 * A
 * A101 (A1)
 * A201 (A2)


 * B
 * B101 (B1)


 * O
 * O01 (O1)
 * O02 (O1v)
 * O03 (O2)

Many rare variants of these alleles have been found in human populations around the world.

Some evolutionary biologists theorize that the IA allele evolved earliest, followed by O (by the deletion of a single nucleotide, shifting the reading frame) and then IB. This chronology accounts for the percentage of people worldwide with each blood type. It is consistent with the accepted patterns of early population movements and varying prevalent blood types in different parts of the world: for instance, B is very common in populations of Asian descent, but rare in ones of Western European descent. Another theory states 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 earliest.

ABO and Rh distribution by country


{| class="wikitable collapsible collapsed" ! Racial & Ethnic Distribution of ABO (without Rh) Blood Types (This table has more entries than the table above but does not distinguish between Rh types.)

Blood group B has its highest frequency in Northern India and neighboring Central Asia, and its incidence diminishes both towards the west and the east, falling to single digit percentages in Spain. It is believed to have been entirely absent from Native American and Australian Aboriginal populations prior to the arrival of Europeans in those areas.

Blood group A is associated with high frequencies in Europe, especially in Scandinavia and Central Europe, although its highest frequencies occur in some Australian Aborigine populations and the Blackfoot Indians of Montana.

Association with von Willebrand factor
The ABO antigen is also expressed on the von Willebrand factor (vWF) glycoprotein, which participates in hemostasis (control of bleeding). In fact, having type O blood predisposes to bleeding, as 30% of the total genetic variation observed in plasma vWF is explained by the effect of the ABO blood group, and individuals with group O blood normally have significantly lower plasma levels of vWF (and Factor VIII) than do non-O individuals. In addition, vWF is degraded more rapidly due to the higher prevalence of blood group O with the Cys1584 variant of vWF (an amino acid polymorphism in VWF): the gene for ADAMTS13 (vWF-cleaving protease) maps to the ninth chromosome (9q34), the same locus as ABO blood type. Higher levels of vWF are more common amongst people who have had ischaemic stroke (from blood clotting) for the first time. The results of this study found that the occurrence was not affected by ADAMTS13 polymorphism, and the only significant genetic factor was the person's blood group.

Disease association
Compared to non-O group (A, AB, and B) individuals, O group individuals have a 14% reduced risk of squamous cell carcinoma and 4% reduced risk of basal cell carcinoma. It is also associated with a reduced risk of pancreatic cancer. The B antigen links with increased risk of ovarian cancer. Gastric cancer has reported to be more common in blood group A and least in group O.

A1 and A2
The A blood type contains about twenty subgroups, of which A1 and A2 are the most common (over 99%). A1 makes up about 80% of all A-type blood, with A2 making up the rest. These two subgroups are interchangeable as far as transfusion is concerned, but complications can sometimes arise in rare cases when typing the blood.

Bombay phenotype
Individuals with the rare Bombay phenotype (hh) do not express antigen H on their red blood cells. As H antigen serves as precursor for producing A and B antigens, the absence of H antigen means the individuals do not have A or B antigens as well (similar to O blood group). However, unlike O group, the H antigen is absent, hence the individuals produce isoantibodies to antigen H as well as to both A and B antigens. In case they receive blood from O blood group, the anti-H antibodies will bind to H antigen on RBC of donor blood and destroy the RBCs by complement-mediated lysis. Therefore Bombay phenotype can receive blood only from other hh donors (although they can donate as though they were type O).

Nomenclature in Europe and former USSR
In parts of Europe, the "O" in ABO blood type is substituted with "0" (zero), signifying the lack of A or B antigen. In the former USSR blood types are referenced using numbers and Roman numerals instead of letters. This is Janský's original classification of blood types. It designates the blood types of humans as I, II, III, and IV, which are elsewhere designated, respectively, as O, A, B, and AB. The designation A and B with reference to blood groups was proposed by Ludwik Hirszfeld.

Examples of ABO and Rhesus D slide testing method
In the slide testing method shown above, three drops of blood are placed on a glass slide with liquid reagents. Agglutination indicates the presence of blood group antigens in the blood.

Universal blood created from other types, and artificial blood
In April 2007, an international team of researchers announced in the journal Nature Biotechnology an inexpensive and efficient way to convert types A, B, and AB blood into type O. This is done by using glycosidase enzymes from specific bacteria to strip the blood group antigens from red blood cells. The removal of A and B antigens still does not address the problem of the Rhesus blood group antigen on the blood cells of Rhesus positive individuals, and so blood from Rhesus negative donors must be used. Patient trials will be conducted before the method can be relied on in live situations.

Another approach to the blood antigen problem is the manufacture of artificial blood, which could act as a substitute in emergencies. BBC.

Conjectures
There are numerous popular conjectures surrounding ABO blood groups. These beliefs have existed since the ABO blood groups were identified and can be found in different cultures throughout the world. For example, during the 1930s, connecting blood groups to personality types became popular in Japan and other areas of the world.

The popularity of Peter J. D'Adamo's book, Eat Right For Your Blood Type suggests that these conjectures persist. This book claims that ABO blood type determines one's optimal diet.

Additional myths include the idea that group A causes severe hangovers, group O is associated with perfect teeth, and those with blood group A2 have the highest IQs. Scientific evidence in support of these concepts is nonexistent.