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Dombrock blood group system, classification of human blood based on the presence of certain glycoproteins, originally only the so-called Do antigens, on the surface of red blood cells. Antibodies to the Dombrock antigen Doa were discovered in 1965 in a patient who had received a blood transfusion; the Do antigen takes its name from the original blood donor. In 1973 a second Dombrock antigen, Dob, was identified; its name is representative of its antithetical relationship to Doa. The Dombrock blood group was expanded in the 1990s to include three other antigens—Gya (Gregory antigen), Hy (Holley antigen), and Joa (Joseph antigen)—that occur on the same protein as the Do antigens.

The Dombrock antigens are located on a glycosylphosphatidylinositol (GPI)-anchored protein that is encoded by the gene ART4 (ADP-ribosyltransferase 4). The GPI is embedded in the membrane of Dombrock-expressing cells, thereby enabling the protein and its antigen-containing residue to remain exposed on the outside surface of the cells. Genetic variations in ART4 that result in an altered amino acid sequence of the encoded protein give rise to the different Dombrock antigens. The Dob antigen is distinguished from the Doa antigen in that it contains an amino acid sequence known as an arginine-glycine-aspartic acid (RGD) motif, which is known to play a role in cell-to-cell interactions.

Studies have indicated that about 65 percent of northern Europeans carry the Doa antigen and that the Dob antigen has an increased incidence in Africans and Asians. In all populations studied, the Gya, Hy, and Joa antigens have been estimated to occur in more than 99 percent of individuals. In addition to the expression of the Doa antigen on circulating red blood cells, it is found on lymphocytes and lymph nodes, in bone marrow, and in the tissues of the spleen, ovaries, testes, intestines, and fetal heart. The expression of Dombrock antigens is highest in the fetal liver. In very rare cases, none of the five Dombrock antigens are expressed on red blood cells, resulting in a Dombrock-null phenotype.

Antibodies to Dombrock antigens have been associated with severe transfusion reactions. In addition, the absence of Dombrock antigens can occur as a result of the loss of GPI-anchored proteins from the surface of red blood cells. The loss of these proteins underlies a rare condition known as paroxysmal nocturnal hemoglobinuria, in which red blood cells undergo premature destruction by immune cells.

Kara Rogers

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blood group, classification of blood based on inherited differences (polymorphisms) in antigens on the surfaces of the red blood cells (erythrocytes). Inherited differences of white blood cells (leukocytes), platelets (thrombocytes), and plasma proteins also constitute blood groups, but they are not included in this discussion.

Historical background

English physician William Harvey announced his observations on the circulation of the blood in 1616 and published his famous monograph titled Exercitatio Anatomica de Motu Cordis et Sanguinis in Animalibus (The Anatomical Exercises Concerning the Motion of the Heart and Blood in Animals) in 1628. His discovery, that blood circulates around the body in a closed system, was an essential prerequisite of the concept of transfusing blood from one animal to another of the same or different species. In England, experiments on the transfusion of blood were pioneered in dogs in 1665 by physician Richard Lower. In November 1667 Lower transfused the blood of a lamb into a man.

Meanwhile, in France, Jean-Baptiste Denis, court physician to King Louis XIV, had also been transfusing lambs’ blood into human subjects and described what is probably the first recorded account of the signs and symptoms of a hemolytic transfusion reaction. Denis was arrested after a fatality, and the procedure of transfusing the blood of other animals into humans was prohibited, by an act of the Chamber of Deputies in 1668, unless sanctioned by the Faculty of Medicine of Paris. Ten years later, in 1678, the British Parliament also prohibited transfusions. Little advance was made in the next 150 years.

In England in the 19th century, interest was reawakened by the activities of obstetrician James Blundell, whose humanitarian instincts had been aroused by the frequently fatal outcome of hemorrhage occurring after childbirth. He insisted that it was better to use human blood for transfusion in such cases.

In 1875 German physiologist Leonard Landois showed that, if the red blood cells of an animal belonging to one species are mixed with serum taken from an animal of another species, the red cells usually clump and sometimes burst—i.e., hemolyze. He attributed the appearance of black urine after transfusion of heterologous blood (blood from a different species) to the hemolysis of the incompatible red cells. Thus, the dangers of transfusing blood of another species to humans were established scientifically.

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The human ABO blood groups were discovered by Austrian-born American biologist Karl Landsteiner in 1901. Landsteiner found that there are substances in the blood, antigens and antibodies, that induce clumping of red cells when red cells of one type are added to those of a second type. He recognized three groups—A, B, and O—based on their reactions to each other. A fourth group, AB, was identified a year later by another research team. Red cells of the A group clump with donor blood of the B group; those of the B group clump with blood of the A group; those of the AB group clump with those of the A or the B group because AB cells contain both A and B antigens; and those of the O group do not generally clump with any group, because they do not contain either A or B antigens. The application of knowledge of the ABO system in blood transfusion practice is of enormous importance, since mistakes can have fatal consequences.

The discovery of the Rh system by Landsteiner and Alexander Wiener in 1940 was made because they tested human red cells with antisera developed in rabbits and guinea pigs by immunization of the animals with the red cells of the rhesus monkey (Macaca mulatta).

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Other blood groups were identified later, such as Kell, Diego, Lutheran, Duffy, and Kidd. The remaining blood group systems were first described after antibodies were identified in patients. Frequently, such discoveries resulted from the search for the explanation of an unexpected unfavorable reaction in a recipient after a transfusion with formerly compatible blood. In such cases the antibodies in the recipient were produced against previously unidentified antigens in the donor’s blood. In the case of the Rh system, for example, the presence of antibodies in the maternal serum directed against antigens present on the child’s red cells can have serious consequences because of antigen-antibody reactions that produce erythroblastosis fetalis, or hemolytic disease of the newborn. Some of the other blood group systems—for example, the Kell and Kidd systems—were discovered because an infant was found to have erythroblastosis fetalis even though mother and child were compatible as far as the Rh system was concerned.

In the table the well-established human blood group systems are listed in the order of discovery.

Major human blood group systems
system date of discovery main antigens
ABO 1901 A1, A2, B, H
MNSs 1927 M, N, S, s
P 1927 P1, P2
Rh 1940 D, C, c, E, e
Lutheran 1945 Lua, Lub
Kell 1946 K, k
Lewis 1946 Lea, Leb
Duffy 1950 Fya, Fyb
Kidd 1951 Jka, Jkb
Diego 1955 Dia, Dib
Yt 1956 Yta, Ytb
I 1956 I, i
Xg 1962 Xga
Dombrock 1965 Doa