ABO blood group system

"H substance" redirects here. For use in inflammation, see histamine.
ABO blood group antigens present on red blood cells and IgM antibodies present in the serum

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 cows and sheep, and apes such as chimpanzees, bonobos, and gorillas.[1]

Contents

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;[2] 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,[3] 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.[4]

Landsteiner described A, B, and O; Decastrello and Sturli discovered the fourth type, AB, in 1902.[5] 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. [6]. Watkins and Morgan, in England, discovered that the ABO epitopes were conferred by sugars, specifically N-acetylgalactosamine for the A-type and galactose for the B-type (Morgan, W. T. J. & Watkins, W. M. Br. Med. Bull. 25, 30–34 (1969), Watkins, W. M. in: Advances in Human Genetics Vol. 10 (eds Harris, H. & Hirschhorn, K.) 1–136 (Plenum, New York, 1980), Watkins, W. M. & Morgan, W. T. J. Vox Sang. 4, 97−119 (1959). 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 (Jarnefelt, Rush, Li, Laine, J. Biol. Chem. 253: 8006–8009(1978)) which contained the major portion of the ABH substances attached (Laine and Rush in Molecular Immunology of Complex Carbohydrates (A. Wu, E. Kabat, Eds.) Plenum Publishing Corporation, N.Y. NY (1988)). Later, Yamamoto's group (Yamamoto, et al., Nature 345, 229–233 (1990)), showed the precise glycosyl transferase set that confers the A, B and O epitopes.

ABO antigens

Diagram showing the carbohydrate chains which determine the ABO blood group

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 slightly from the A allele by deletion of a single nucleotide - Guanine at position 261. The deletion causes a frameshift and results in translation of an almost entirely different protein that lacks enzymatic activity. 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. It is possible that food and environmental antigens (bacterial, viral or plant antigens) have epitopes similar enough to A and B glycoprotein antigensThe antibodies created against these environmental antigens in the first years of life can cross react with ABO-incompatible red blood cells when it comes in contact with during blood transfusion later in life. 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.

The "Light in the Dark theory" (DelNagro, 1998) suggests that when budding viruses take with them 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. [7] [8]

The "Light in the Dark theory" suggests a new novel evolutionary hypothesis that 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.

Transfusion Reactions

Due to the presence of isoantibodies against non self blood group antigens, individuals of type A blood group immediately raises anti-B antibodies against B-blood group RBCs if transfused with blood from B group. The anti-B antibodies bind to B antigens on RBC and causes 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.

One caveat to this axiom of 'universal donor' is that this applies to packed RBC's 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.

recipient donor
A A or O
B B or O
AB A, B, AB, or O
O O

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.[9]

ABO hemolytic disease of the newborn

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 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

A and B are codominant, giving the AB phenotype.
Blood group inheritance
Mother/Father O A B AB
O O O, A O, B A, B
A O, A O, A O, A, B, AB A, B, AB
B O, B O, A, B, AB O, B A, B, AB
AB A, B A, B, AB A, B, AB A, B, AB

Blood groups are inherited from both parents. The ABO blood type is controlled by a single 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) Therefore, an O child is not a direct proof of illegitimacy, just as a child with blond hair could be born from parents who both had brown hair. 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.[10]

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.[11]

There are six common alleles of the ABO gene that produce one's blood type:[12][13]

A
  • A101 (A1)
  • A201 (A1)
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[14]. 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[14]. Both theories, contradict the previously-held theory that type O blood evolved earliest, supported by the fact that all human beings can receive it. The British National Blood Transfusion Service states this to be the case (see the web-link under External Links below) and says that originally all human beings were type O.

Association with von Willebrand factor

The ABO antigen is also expressed on the von Willebrand factor (vWF) glycoprotein,[15] which participates in hemostasis (control of bleeding). In fact, having type O blood predisposes to bleeding,[16] as 30% of the total genetic variation observed in plasma vWF is explained by the effect of the ABO blood group,[17] and individuals with group O blood normally have significantly lower plasma levels of vWF (and Factor VIII) than do non-O individuals.[18][19] 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):[20] 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.[21] 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.

Subgroups

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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.[22] These two subgroups are interchangeable as far as transfusion is concerned, however complications can sometimes arise in rare cases when typing the blood.[22]

Bombay phenotype

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 H antigen is absent, hence the individuals produce isoantibodies to antigen H as well as to both A and B antigens. In case they recieve 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.[23] 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. [24] 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 creation of artificial blood which could act as a substitute in emergencies. BBC.

Myths

There are numerous popular myths 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.[25]

The popularity of Peter J. D'Adamo's book, Eat Right For Your Blood Type suggests that these myths persist. This book claims that ABO blood groups can be used to determine diet as well as to predict diseases.

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 scant or nonexistent.[26]

References

  1. ↑ Maton, Anthea; Jean Hopkins, Charles William McLaughlin, Susan Johnson, Maryanna Quon Warner, David LaHart, Jill D. Wright (1993). Human Biology and Health. Englewood Cliffs, New Jersey, USA: Prentice Hall. ISBN 0-13-981176-1. 
  2. ↑ Landsteiner K (1900). "Zur Kenntnis der antifermentativen, lytischen und agglutinierenden Wirkungen des Blutserums und der Lymphe". Zentralblatt Bakteriologie 27: 357–62. 
  3. ↑ Janský J (1907). "(Haematologick studie u. psychotiku" (in Czech). Sborn. Klinick 8: 85–139. 
  4. ↑ Moss WL (1910). "Studies on isoagglutinins and isohemolysins". Bulletin Johns Hopkins Hospital 21: 63–70. 
  5. ↑ von Decastello A, Sturli A (1902). "Ueber die Isoagglutinine im Serum gesunder und kranker Menschen". Mfinch med Wschr 49: 1090–5. 
  6. ↑ Crow J (1993). "Felix Bernstein and the first human marker locus". Genetics 133 (1): 4–7. PMID 8417988.  Full text at PMC: 1205297
  7. ↑ Arendrup, M; Hansen JE, Clausen H, Nielsen C, Mathiesen LR, Nielsen JO (April 1991). "Antibody to histo-blood group A antigen neutralizes HIV produced by lymphocytes from blood group A donors but not from blood group B or O donors". AIDS 5 (4): 441–4. PMID 1711864. 
  8. ↑ Neil, SJ; McKnight A, Gustafsson K, Weiss RA (2005-06-15). "HIV-1 incorporates ABO histo-blood group antigens that sensitize virions to complement-mediated inactivation". Blood 105 (12): 4693–9. doi:10.1182/blood-2004-11-4267. PMID 15728127. http://bloodjournal.hematologylibrary.org/cgi/content/full/105/12/4693. 
  9. ↑ Laine, R.A. and Rush, J.S. (1988) "Chemistry of Human Erythrocyte Polylactosamine Glycopeptides (Erythroglycans) as Related to ABH Blood Group antigenic Determinants: Evidence that Band 3 Carbohydrate on Human Erythrocytes Carries the Majority of ABH Blood Group Substance" in Molecular Immunology of Complex Carbohydrates (A. Wu, E. Kabat, Eds.) Plenum Publishing Corporation, N.Y. NY.
  10. ↑ Yazer M, Olsson M, Palcic M (2006). "The cis-AB blood group phenotype: fundamental lessons in glycobiology". Transfus Med Rev 20 (3): 207–17. doi:10.1016/j.tmrv.2006.03.002. PMID 16787828. 
  11. ↑ Potts, WTW (1979). "History and Blood Groups in the British Isles". in Sawyer PH. English Medieval Settlement. St. Martin's Press. ISBN 0-7131-6257-0. 
  12. ↑ Seltsam A, Hallensleben M, Kollmann A, Blasczyk R (2003). "The nature of diversity and diversification at the ABO locus". Blood 102 (8): 3035–42. doi:10.1182/blood-2003-03-0955. PMID 12829588. 
  13. ↑ Ogasawara K, Bannai M, Saitou N, et al (1996). "Extensive polymorphism of ABO blood group gene: three major lineages of the alleles for the common ABO phenotypes". Human Genetics 97 (6): 777–83. doi:10.1007/BF02346189. PMID 8641696. 
  14. ↑ 14.0 14.1 Calafell, Francesc; et al (September 2008). "Evolutionary dynamics of the human ABO gene". Human Genetics 124 (2): 123–135. doi:10.1007/s00439-008-0530-8. PMID 18629539. http://www.springerlink.com/content/yv4072vu67mv1166/fulltext.html. Retrieved on 2008-09-24. 
  15. ↑ Sarode, R; Goldstein J, Sussman II, Nagel RL, Tsai HM (June 2000). "Role of A and B blood group antigens in the expression of adhesive activity of von Willebrand factor". Br J Haematol. 109 (4): 857–64. doi:10.1046/j.1365-2141.2000.02113.x. PMID 10929042. 
  16. ↑ O'Donnell, J; Laffan MA (August 2001). "The relationship between ABO histo-blood group, factor VIII and von Willebrand factor". Transfus Med. 11 (4): 343–51. doi:10.1046/j.1365-3148.2001.00315.x. PMID 11532189. 
  17. ↑ O'Donnell, J; Boulton FE, Manning RA, Laffan MA (2002-02-01). "Amount of H antigen expressed on circulating von Willebrand factor is modifiedby ABO blood group genotype and is a major determinant of plasma von Willebrand factor antigen levels". Arterioscler Thromb Vasc Biol. (American Heart Association, Inc.) 22 (2): 335–41. doi:10.1161/hq0202.103997. PMID 11834538. http://atvb.ahajournals.org/cgi/content/full/22/2/335. 
  18. ↑ Gill, JC; Endres-Brooks J, Bauer PJ, Marks WJ, Montgomery RR (June 1987). "The effect of ABO blood group on the diagnosis of von Willebrand disease" (abstract). Blood 69 (6): 1691–5. PMID 3495304. http://www.bloodjournal.org/cgi/content/abstract/69/6/1691. 
  19. ↑ Shima, M; Fujimura Y, Nishiyama T et. al (1995). "ABO blood group genotype and plasma von Willebrand factor in normal individuals". Vox Sang 68 (4): 236–40. PMID 7660643. 
  20. ↑ Bowen, DJ; Collins PW, Lester W, et. al (March 2005). "The prevalence of the cysteine1584 variant of von Willebrand factor is increased in type 1 von Willebrand disease: co-segregation with increased susceptibility to ADAMTS13 proteolysis but not clinical phenotype". Br J Haematol (Blackwell Synergy) 128 (6): 830–6. doi:10.1111/j.1365-2141.2005.05375.x. PMID 15755288. 
  21. ↑ Bongers T, de Maat M, van Goor M, et. al (2006). "High von Willebrand factor levels increase the risk of first ischemic stroke: influence of ADAMTS13, inflammation, and genetic variability". Stroke 37 (11): 2672–7. doi:10.1161/01.STR.0000244767.39962.f7. PMID 16990571. 
  22. ↑ 22.0 22.1 Blood Group A Suptypes, The Owen Foundation, retrieved 2008-07-01.
  23. ↑ Erb IH (1940). "Blood Group Classifications, a Plea for Uniformity". Canadian Medical Association Journal 42 (5): 418–21. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=537907. 
  24. ↑ Liu, QP; Sulzenbacher G, Yuan H, Bennett EP, Pietz G, Saunders K, Spence J, Nudelman E, Levery SB, White T, Neveu JM, Lane WS, Bourne Y, Olsson ML, Henrissat B, Clausen H (April 2007). "Bacterial glycosidases for the production of universal red blood cells". Nat Biotechnol 25 (4): 454–64. doi:10.1038/nbt1298. PMID 17401360. http://www.nature.com/nbt/journal/v25/n4/abs/nbt1298.html. 
  25. ↑ American Red Cross, Southern California Blood Services Region (n.d.). "Answers to Commonly Asked Questions About Blood and Blood Banking" (PDF). Blood: The Basics: 4. http://www.socalredcross.org/pdf/BloodThe.pdf. Retrieved on 2007-11-16. 
  26. ↑ Klein, Harvey G (March 7, 2005). "Why Do People Have Different Blood Types?". Scientific American. http://www.sciam.com/article.cfm?id=why-do-people-have-differ. Retrieved on 2007-11-16. 

Further reading

External links

Transfusion medicine
General concepts
Apheresis  (Plasmapheresis, Plateletpheresis, Leukapheresis) - Blood transfusion - Coombs test - Cross-matching - Exchange transfusion - International Society of Blood Transfusion - Intraoperative blood salvage - ISBT 128 - Transfusion reactions
Human blood group systems  - Blood type
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