abo blood group system 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 44 different blood type (or group) classification systems currently recognized by the international society of blood transfusions (isbt) as of december 2022. a mismatch (very rare in modern medicine) in this, or any other serotype, can cause a potentially fatal adverse reaction after a transfusion, or an unwanted immune response to an organ transplant. 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. abo blood group antigens present on red blood cells and igm antibodies present in the serum 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 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 (now medical university of vienna). in 1900, he found that red blood cells would clump together (agglutinate) 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: the serum of healthy human beings not only agglutinates animal red cells, but also often those of human origin, from other individuals. it remains to be seen whether this appearance is related to inborn differences between individuals or it is the result of some damage of bacterial kind. 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 (antibodies), which is the actual basis of antigen-antibody reaction in the abo system. he asserted: may be said that there exist at least two different types of agglutinins, one in a, another one in b, and both together in c. the red blood cells are inert to the agglutinins which are present in the same serum. thus, he discovered two antigens (agglutinogens a and b) and two antibodies (agglutinins – anti-a and anti-b). his third group (c) 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 (but not naming it, and simply referred to it as "no particular type"). ukraine marine uniform imprint, showing the wearer's blood type as "b (iii) rh+" in 1910, ludwik hirszfeld and emil freiherr von dungern introduced the term o (null) 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 jan janský, who invented type i, ii, iii, iv system 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 (corresponding to modern o, a, b, and ab). 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. (there was another confusion on the use of figure 0 for german null as introduced by hirszfeld and von dungern, because others used the letter o for ohne, meaning without or zero; landsteiner chose the latter.) 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 (1914–1915) 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. (1978) 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. diagram showing the carbohydrate chains that determine the abo blood group student blood test. three drops of blood are mixed with anti-b (left) and anti-a (right) serum. agglutination with anti-a suggests this individual is type a. there are three basic variants of immunoglobulin antigens in humans that share a very similar chemical structure but are distinctly different. red circles show where there are differences in chemical structure in the antigen-binding site (sometimes called the antibody-combining site) of human immunoglobulin. notice the o-type antigen does not have a binding site. genetics a and b are codominant, giving the ab phenotype. blood groups are inherited from both parents. the abo blood type is controlled by a single gene (the abo gene) with three types of alleles inferred from classical genetics: i, ia, and ib. 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 (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 couple with type a and type b can also have a type o child if they are both heterozygous (ibi and 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. blood group inheritance blood type o a b ab genotype ii (oo) iai (ao) iaia (aa) ibi (bo) ibib (bb) iaib (ab) o ii (oo) ooo oo oo oo o or aao oo ao oo aao ao ao ao o or bbo oo bo oo bbo bo bo bo a or bao bo ao bo a iai (ao) o or aao ao oo oo o or aaa ao ao oo aaa aa ao ao o, a, b or abab ao bo oo b or abab ab bo bo a, b or abaa ab ao bo iaia (aa) aao ao ao ao aaa ao aa ao aaa aa aa aa a or abab ao ab ao abab ab ab ab a or abaa ab aa ab b ibi (bo) o or bbo bo oo oo o, a, b or abab bo ao oo a or abab ab ao ao o or bbb bo bo oo bbb bb bo bo a, b or abab bb ao bo ibib (bb) bbo bo bo bo b or abab bo ab bo abab ab ab ab bbb bo bb bo bbb bb bb bb b or abab bb ab bb ab iaib (ab) a or bao ao bo bo a, b or abaa ao ab bo a or abaa aa ab ab a, b or abab ao bb bo b or abab ab bb bb a, b, or abaa ab ab bb 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. blood group inheritance by phenotype only blood type o a b ab o o o or a o or b a or b a o or a o or a o, a, b or ab a, b or ab b o or b o, a, b or ab o or b a, b or ab ab a or b a, b or ab a, b or ab a, b or ab 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 (over 99%). 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: abo a101 (a1)a201 (a2) b101 (b1) o01 (o1)o02 (o1v)o03 (o2) 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 genes are transmitted together from a