ABO BLOOD GROUP SYSTEMs

The ABO blood group system is the most important blood type system (or blood group system) in human blood transfusion. The associated anti-A 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 other animals, for example apes such [1] as chimpanzees, bonobos, and gorillas.
Contents
[hide]

1 History of discoveries 2 ABO antigens 3 Serology

3.1 Origin theories

4 Nonantigen biology 5 Transfusion reactions 6 ABO hemolytic disease of the newborn 7 Inheritance 8 Distribution and evolutionary history

o o

8.1 Genetics 8.2 ABO and Rh distribution by country

9 Association with von Willebrand factor 10 Disease association 11 Subgroups

11.1 A1 and A2

12 Bombay phenotype 13 Nomenclature in Europe and former USSR 14 Examples of ABO and Rhesus D slide testing method 15 Universal blood created from other types, and artificial blood 16 Pseudoscience 17 See also 18 References 19 Further reading 20 External links

History of discoveries [edit]

The ABO blood group system is widely credited to have been discovered by the Austrian scientist Karl [2] 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 Jansk had independently pioneered the classification of [3] human blood into four groups, but Landsteiner's independent discovery had been accepted by the scientific world while Jansk remained in relative obscurity. Jansk's classification is however still used in Russia and states of former USSR (see below). In America, W.L. Moss published his own (very similar) [4] work in 1910. Landsteiner described A, B, and O; Alfred von Decastello and Adriano Sturli discovered the fourth type, [5] AB, in 1902. Ludwik Hirszfeld and E. von Dungern discovered the heritability of ABO blood groups in 191011, with Felix Bernstein demonstrating the correct blood group inheritance pattern of [6] 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 [7][8][9] 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 [10] [11] polylactosamine chain that contains the major portion of the ABH substances attached. Later, [12] Yamamoto's group showed the precise glycosyl transferase set that confers the A, B and O epitopes.

ABO antigens [edit]

Diagram showing the carbohydrate chains that determine the ABO blood group

The H antigen is an essential precursor to the ABO blood group antigens. The H locus, which is located on chromosome 19, contains three exons that span more than 5 kb of genomic DNA; 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 -D-galactose, -D-N-acetylglucosamine, -D-galactose, and 2-linked, -L-fucose, the chain being attached to the protein or ceramide.

The ABO locus, which is located on chromosome 9, 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 aglycosyltransferase that bonds -Nacetylgalactosamine to the D-galactose end of the H antigen, producing the A antigen. The B allele encodes a glycosyltransferase that bonds -D-galactose to the D-galactose end of the H antigen, creating the B antigen. In the case of the O allele, when compared to the A allele, exon 6 lacks one nucleotide (guanine), which results in a loss of enzymatic activity. This difference, which occurs at position 261, causes a frameshift that results in the premature termination of the translation and, thus, degradation of the mRNA. This results in the 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 glycosphingolipid.

Serology [edit]
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 [edit]

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 (RBCs) 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 -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 [13] as E. coli, cross-reacting with the -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 [14][15] 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 [citation needed] recessive alleles.

However, it is more likely that the force driving evolution of allele diversity is simply negative frequencydependent 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 [16] populations would, then, be a consequence of natural selection on individuals.

Nonantigen biology [edit]

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 [17][18] enzymes. ABO antigens are found having similar roles on epithelial cells as well as red blood cells.

Transfusion reactions [edit]

For a blood donor and recipient to be ABO-compatible for a transfusion, the recipient cannot be able to produce Anti-A or Anti-B antibodies that correspond to the A or B antigens on the surface of the donor's red blood cells (since the red blood cells are isolated from whole blood before transfusion, it is unimportant whether the donor blood has antibodies in its plasma). If the antibodies of the recipient's blood and the antigens on the donor's red blood cells do correspond, the donor blood is rejected. In addition to the ABO system, the Rh blood group system can affect transfusion compatibility. An individual is either positive or negative for the Rh factor; this is denoted by a '+' or '-' after their ABO type. Blood that is Rh-negative can be transfused into a person who is Rh-positive, but an Rh-negative individual can create antibodies for Rh-positive RBCs. Because of this, the AB+ blood type is referred to as the "universal recipient" (marked by * below), as it possesses neither Anti-B or Anti-A antibodies in its plasma, and can receive both Rh-positive and Rhnegative blood. Similarly, the O- blood type is called the "universal donor" (marked by ** below); since its red blood cells have no A or B antigens and are Rh-negative, no other blood type will reject it.

ABO and Rh blood type donation showing matches between donor and recipient types

Donors

O+

A+

B+

AB+

O- **

A-

B-

AB-

O+ Recipients A+

B+

AB+ *

O-

A-

B-

AB-

ABO hemolytic disease of the newborn [edit]

Main article: Hemolytic disease of the newborn (ABO) 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 theIgM 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 [edit]

A and B are codominant, giving the AB phenotype.

Blood groups are inherited from both parents. The ABO blood type is controlled by a A B single gene (the ABO gene) with three alleles: i, I , andI . The gene encodes a glycosyltransferasethat 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 I allele gives type A, I gives type B, and i gives type O. As both I and I are dominant over i, A A A only ii people have type O blood. Individuals with I I or I i have type A blood, and individuals B B B A B with I I or I i have type B. I I 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 B A type A and a type B couple can also have a type O child if they are both heterozygous ( I i,I i) The cisAB 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 A 1 or B [19] red blood cells, which can help solve the problem of an apparently genetically impossible blood group.
A B A B

Distribution and evolutionary history [edit]

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 [20] 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:
[21][22]

A101 (A1) B101 (B1) O01 (O1) A201 (A2) O02 (O1v) O03 (O2)

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

Genetics [edit]
There are two common O alleles, O01 and O02. These are identical to the group A allele (A01) for the first 261 nucleotides, at which point a guanosine base is deleted, resulting in a frame-shift mutation that produces a premature stop codon and failure to produce a functional A or B transferase. This deletion is found in all populations worldwide and presumably arose before humans migrated out of Africa (50,000 to 100,000 years ago). The second most common allele for group O (termed O02) is considered to be an even more ancient than the O01 allele. Some evolutionary biologists theorize that the I allele evolved earliest, followed by O (by the deletion of a B [citation needed] single nucleotide, shifting the reading frame) and then I . This chronology accounts for the
A [23]

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 [24] occurred at least three times in humans. From oldest to youngest, these lineages comprise the following alleles: A101/A201/O09, B101, O02and O01. The continued presence of the O alleles is [24] 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 [edit]

Frequency of O group in indigenous populations around the world

ABO and Rh blood type distribution by country (population averages)

Country

Population

[25]

O+

A+

B+

AB+

O-

A-

B-

AB-

Australia

[26]

21,262,641

40.0%

31.0%

8.0%

2.0%

9.0%

7.0%

2.0%

1.0%

Austria

[27]

8,210,281

30.0%

33.0%

12.0%

6.0%

7.0%

8.0%

3.0%

1.0%

Belgium

[28]

10,414,336

38.0%

34.0%

8.5%

4.1%

7.0%

6.0%

1.5%

0.8%

Brazil

[29]

198,739,269

36.0%

34.0%

8.0%

2.5%

9.0%

8.0%

2.0%

0.5%

Canada

[30]

33,487,208

39.0%

36.0%

7.6%

2.5%

7.0%

6.0%

1.4%

0.5%

ABO and Rh blood type distribution by country (population averages)

Country

Population

[25]

O+

A+

B+

AB+

O-

A-

B-

AB-

China

[31]

1,339,724,852

47.7%

27.8%

18.9%

5.0%

0.3%

0.2%

0.1% 0.03%

Czech Republic

[32]

10,532,770

27.0%

36.0%

15.0%

7.0%

5.0%

6.0%

3.0%

1.0%

Denmark

[33]

5,500,510

35.0%

37.0%

8.0%

4.0%

6.0%

7.0%

2.0%

1.0%

Estonia

[34]

1,299,371

41.0%

31.0%

8.0%

4.0%

8.0%

5.9%

1.2%

0.9%

Finland

[35]

5,250,275

27.0%

38.0%

15.0%

7.0%

4.0%

6.0%

2.0%

1.0%

France

[36]

62,150,775

36.0%

37.0%

9.0%

3.0%

6.0%

7.0%

1.0%

1.0%

Germany

[37]

82,329,758

35.0%

37.0%

9.0%

4.0%

6.0%

6.0%

2.0%

1.0%

Hong Kong SAR

[38]

7,055,071 41.51% 26.13% 25.34%

6.35% 0.32% 0.17% 0.14% 0.05%

Iceland

[39]

306,694

47.6%

26.4%

9.3%

1.6%

8.4%

4.6%

1.7%

0.4%

Ireland

[40]

4,203,200

47.0%

26.0%

9.0%

2.0%

8.0%

5.0%

2.0%

1.0%

Israel

[41]

7,233,701

32.0%

34.0%

17.0%

7.0%

3.0%

4.0%

2.0%

1.0%

Korea

[42]

73,000,000

36.6%

32.8%

21.0%

9.0%

0.4%

0.2% 0.09% 0.03%

ABO and Rh blood type distribution by country (population averages)

Country

Population

[25]

O+

A+

B+

AB+

O-

A-

B-

AB-

Netherlands

[43]

16,715,999

39.5%

35.0%

6.7%

2.5%

7.5%

7.0%

1.3%

0.5%

New Zealand

[44]

4,213,418

38.0%

32.0%

9.0%

3.0%

9.0%

6.0%

2.0%

1.0%

Norway

[45]

4,660,539

34.0%

42.5%

6.8%

3.4%

6.0%

7.5%

1.2%

0.6%

Poland

[46]

38,482,919

31.0%

32.0%

15.0%

7.0%

6.0%

6.0%

2.0%

1.0%

Portugal

[47]

10,707,924

36.2%

39.8%

6.6%

2.9%

6.0%

6.6%

1.1%

0.5%

Saudi Arabia

[48]

28,686,633

48.0%

24.0%

17.0%

4.0%

4.0%

2.0%

1.0%

0.3%

South Africa

[49]

49,320,000

39.0%

32.0%

12.0%

3.0%

7.0%

5.0%

2.0%

1.0%

Spain

[50]

40,525,002

36.0%

34.0%

8.0%

2.5%

9.0%

8.0%

2.0%

0.5%

Sweden

[51]

9,059,651

32.0%

37.0%

10.0%

5.0%

6.0%

7.0%

2.0%

1.0%

Turkey

[52]

76,805,524

29.8%

37.8%

14.2%

7.2%

3.9%

4.7%

1.6%

0.8%

United Kingdom

[53]

61,113,205

37.0%

35.0%

8.0%

3.0%

7.0%

7.0%

2.0%

1.0%

United States

[54]

307,212,123

37.4%

35.7%

8.5%

3.4%

6.6%

6.3%

1.5%

0.6%

ABO and Rh blood type distribution by country (population averages)

Country

Population

[25]

O+

A+

B+

AB+

O-

A-

B-

AB-

Weighted mean

2,261,025,244

36.4%

28.3%

20.6%

5.1%

4.3%

3.5%

1.4%

0.5%

50.0% and above 40.049.9% 30.039.9% 20.029.9% 10.019.9% 5.09.9% [show]Racial & Ethnic Distribution of ABO (without Rh) Blood Types
[55]

(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 [56][57] 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 [57][58] 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 [59][60] Blackfoot Indians of Montana. Additional sources.
[61][62]

Association with von Willebrand factor [edit]

The ABO antigen is also expressed on the von Willebrand factor (vWF) glycoprotein, which participates [64] in hemostasis (control of bleeding). In fact, having type O blood predisposes to bleeding, as 30% of the [65] 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) [66][67] than do non-O individuals. In addition, vWF is degraded more rapidly due to the higher prevalence of [68] 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 [69] 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.
[63]

Disease association [edit]

Compared to non-O group (A, AB, and B) individuals, O group individuals have a 14% reduced risk [70] of squamous cell carcinoma and 4% reduced risk of basal cell carcinoma. It is also associated with a [71][72] reduced risk of pancreatic cancer. The B antigen links with increased risk of ovarian [73] [74] cancer. Gastric cancer has reported to be more common in blood group A and least in group O.

According to Glass, Holmgren, et al., those in the O blood group have an increased risk of infection with cholera, and those O-group individuals who are infected have more severe infections. The mechanisms behind this association with cholera are currently unclear in the literature. The title of the referenced article is: "Predisposition for cholera of individuals with O blood group. Possible evolutionary [75] significance."

Subgroups [edit]
This section requires expansion.(October 2009)

A1 and A2 [edit]
The A blood type contains about twenty subgroups, of which A1 and A2 are the most common (over [76] 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 [76] cases when typing the blood.

Bombay phenotype [edit]

Main article: Hh antigen system 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 [edit]

Ukraine marine uniform imprint, showing the wearer's blood type as "B (III) Rh+"

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 Jansk's original classification of blood types. It designates the blood types of humans as I, [77] 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 [edit]

Blood group O positive: neither anti-A nor anti-B have agglutinated, but anti-Rh has

Result: Blood group A positive: anti-A and anti-Rh have agglutinated but anti-B has not.

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 [edit]
In April 2007, an international team of researchers announced in the journal Nature Biotechnology an [78] 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 theRhesus 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 [79] substitute in emergencies.

Pseudoscience [edit]
Peter J. D'Adamo's book, Eat Right For Your Blood Type, offers a history of human blood type development and claims that ABO blood groups can be used to determine the proper diet for your body to maintain its proper balance, as well as to predict personality traits and disease susceptibility. No published research is referenced, indicating that the information is not supported by any scientific evidence. During the 1930s, connecting blood groups to personality types became popular in Japan and other areas [80] of the world. Additional ideas include: 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 [81] virtually nonexistent.