ABO Blood Antigens
Our ABO Blood Antigens range includes the products shown in Table 1.
The discovery that the red blood cells (RBCs) of some people were agglutinated by soluble factors in the serum of other people led to the discovery of the ABO blood group systems, and that blood transfusions between persons with the same blood group did not lead to the destruction of blood cells, unlike those between persons of different blood groups earned Karl Landsteiner a Noble prize in medicine1. Non-matching blood groups are rejected after transfusion because the immune system forms natural antibodies against whichever ABO blood group antigens are not found on the individual's RBCs. These ABO antibodies in serum are formed naturally and their production is thought to be stimulated when the immune system encounters the "missing" ABO blood group antigens in foods or in micro-organisms. Figure 1 shows the terminal structure of the A B and O antigens. It should be noted that although best known as blood antigens these antigens are expressed on most tissues of the body and on epithelial and endothelial cells2.
Figure 1 Structures of A, B, and O Oligosaccharide Antigens
Abbreviations: Fuc=L-fucose; Gal=D-galactose; GalNAc = N-acetylgalactosamine ; GlcNAc = N-acetylglucosamine.
The A, B, and H antigens are formed by the sequential action of glycosyltransferases which are encoded by four genes (the A, B, H, and Secretor [Se] genes).
The H antigen is the first structure to be synthesised with the modification of the core Gal-b
-1,3-Gal structure by the action of two a
-1,2-FucT). If the core structure is on red blood cell precursors the H gene (gene code: FUT1) a
-1,2-FucT adds a terminal fucose to complete the blood group H antigen (product codes OB05907 or OB08358). If the core structure occurs on epithelia tissue e.g. the lining of the lumen of the gastrointestinal, respiratory, and reproductive tracts and in salivary glands then the Secretor a
-1,2-FucT enzyme (gene code FUT2) will add fucose. All of these tissues can secrete soluble antigen into body fluids, tissues or saliva and individuals positive for the Se gene are known as Secretors.3
Secretor status is often a useful forensic indictor used to include or exclude suspects in police enquiries (Se is a dominant gene and approximately 85% of all people are Secretors).
A and B blood group antigens are then synthesised by the action two glycosyltransferases. The blood group A glycan (product codes OB04438, OB03872 or OB06035) is formed by the action of an a
and the blood group B glycan (product codes OB01663, OB03859 or OB07521) by an a
-1,3-Gal transferase. These two enzymes are encoded by different versions, or alleles, of the same gene: A and B. The O genes codes for an inactive A and B glycosyl transferase therefore blood group O individuals express unmodified H antigen5
. Since the A and B genes are co-dominant a person with copies of both genes are blood group AB.
Like the H antigen, A and B antigens are expressed on membrane glycoproteins and glycolipids on the surface of red cells and other cells in many tissues, including the vascular endothelium and a variety of epithelia. Again like the H antigen some tissues also synthesize soluble, secreted forms of these molecules as glycans on secreted glycoproteins, glycolipids, and as free glycans.6
The Bombay Phenotype7
An individual may not possess a working H gene (which adds the terminal fucose) and therefore do not produce any H antigen. As the H antigen is an essential precursor to the ABO blood group antigens they cannot produce A and B antigens. These individuals produce anti-A and anti-B, and potent anti-H antibodies. This rare phenotype of H-deficient RBCs is called the "Bombay phenotype" (Oh) after the city in which it was first discovered. Individuals with the Bombay phenotype are healthy, but if they ever needed a blood transfusion, the antibodies in their serum would place them at a high risk of having an acute haemolytic transfusion reaction. This can be avoided by using only blood products from a donor who also has the Bombay phenotype (usually a relative).
Beyond Blood Typing
The blood group sugars are seeing increasing use beyond blood type laboratories in a wide variety of applications. Solid phase A/B matrices are used to remove cross reacting antibodies from patient antisera, allowing for organ transplant in ABO mismatched patients potentially doubling the availability of organ donors.8,9
Carrier conjugates and free ABH sugars have been used to determine lectin specificity10
, specificity of anti ABH monoclonal antibodies11
and enzyme-linked immunosorbent assays for the measurement of blood group A and B glycosyltransferase activities (along with UDP-Gal and UDP-GalNAc). Latex particles or other surfaces coated with A glycans have been used to enrich pathogens in media prior to assay by ELISA or Biosensor.12
2. Dean. Blood Cell and Red Cell antigens: NCBI Webook: http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=rbcantigen&part=ch05ABO
3. Stanley and Cummings, Structures Common to Different Glycans, In Essentials of Glycobiology 2nd Edition 2008, Cold Spring Harbor Laboratory Press.
4. Hearn, V. M., et al, Biochem. J. 1968, 109, 315.
5. Yamamoto F. ABO blood group system—ABH oligosaccharide antigens, anti-A and anti-B, A and B glycosyltransferases, and ABO genes. Immunohematol. 2004, 20, 3.
6. Szulman, A. E. J. Exper. Med. 1960, 111, 785.
7. Hakim, S.A. et al. Transfusion. 1961, 1, 218.
8. Rieben R et al. Transplantation. 1995, 60(5), 425.
9. Rydberg et al. Transplant Intl. 2004, 17(11), 666.
10. Matsui T, et al Biochim Biophys Acta 2001,1525(1-2), 50.
11. Rieben R et al Transfus Clin Biol. 1997, 4(1), 47.
12. Nilsson et. al, J. Immunol. Meth. 1988, 108, 237.