Introduction
There are 19 known blood group systems encompassing over 200 antigens. Only two of these, however, (the ABO and the Rh) can commonly causehaemolytic transfusion reaction (HTR) as well as haemolytic disease of the newborn (HDN). Several other systems (Kell, Duffy, Kidd) can occasionally determine HTR and HDN. Two other systems (P and MN) very rarely cause HTR and HDN and the Lutheran and Lewis systems rarely cause HTR but not HDN. Current understanding of the serology and genetics of the major blood group antigens has enabled prevention of both HTR and HDN and this understanding forms the topic of this lecture.
The ABO, Hh and Lewis groups
These three groups are discussed together because, although genetically distinct, they are biochemically closely related (complex carbohydrates). The first two groups (ABO and Hh) are classsic blood groups: they reflect the presence of antigenic determinants associated with consituents of the red cell membrane. The antigens of the Lewis groups are due to the absorption of soluble antigenic determinants on the red cell surface.
The ABO system was discovered by K Landsteiner in 1900 when, on the strength of experiments carried out with serum and blood cells from different species, he performed a series of mixing experiments with the blood of 22 colleagues in which red cells from each individual were mixed with the serum of each of the others. On the basis of the agglutination pattern that he observed, Landsteiner could establish three groups of individuals (A,B and C). The red cells of group A individuals were agglutinated by the serum of group B and C individuals, the red cells of group B individuals were agglutinated by the serum of group A and C individuals and the red cells of group C individuals were not agglutinated by the serum from any individual. Two years later, Landsteiner recognised a fourth (AB) group when the experiment was repeated on a larger group of subjects. The presence of subgroups of A, one of which exhibiting weaker expression of the A antigen was noted in 1911 and K Landsteiner named the two subgroups A1 and A2.
Blood group A and B individuals are characterized by the presence of specific tri-saccharide structures known as A and B antigens respectively. Blood group O individuals express H antigen, the precursor of A and B antigens. H antigen is also expressed to a smaller extent in A and B blood cells but is not expressed in the rare 'Bombay' population.
The ABH antigens are not confined to red blood cells. They are present at much higher density in epithelial cells (especially glandular epithelia and their secretory products, see below) and endothelial cells. They are, therefore, importanthistocompatibility antigens. Indeed, chemical characterisation of the ABH (as well as Lea and Leb antigens) was carried out initially (in the 50s and 60s) on epithelium-derived material by Morgan, Watkins and colleagues in the UK and by Kabat and colleagues in the USA. The chemical nature of the ABH antigens present in erythrocytes was elucidated later. Red blood cell's ABH antigens are present both as glycosphingolipids as well as glycoproteins (especially in bands 3 and 4.5). ABH antigens are carried by four main types of carrier carbohydrate chain (1-4) as detailed in the Table Main types of carrier sequences of ABO antigens.
There are several structural variants of type 1 and type 2 chain A antigen in terms of fucosyl substitutions. Similar variants can be found for B antigens. Type 2 chain can be either branched or unbranched. Unbranched type 2 chain is predominant in fetal and newborn cells and corresponds to the classical i antigen. Branched type 2 chain is predominant in adult cells and corresponds to classical I antigen. There are two serological subgroups of A: A1 (~80% of A subjects, corresponding to the original Landsteiner A group and A2 (~20% of A subjects). The A2 subjects have much weaker expression of A and their serum frequently contain antibodies to the A determinant. The A determinant carried by type 1 and 2 chain is present in greater quantity in A1 than in A2 cell. The A determinant carried by type 3 or type 4 chain is abundant in type A1 cells but absent in type A2. Thus the difference between A1 and A2 is both quantitative and qualitative.
Source : http://nfs.unipv.it/nfs/minf/dispense/immunology/lectures/files/blood_groups.html
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