“This is what even a child can answer”, we might think. “There is the famous ABO classification, and then the Rh , which can be positive or negative … and that’s it.” But the truth is that the matter is much more complicated than it seems at first glance.
Blood groups behave like antigens
Let’s start by clarifying the concept. Blood groups are found in the proteins and carbohydrates that are part of the membrane of the red blood cells, the blood cells responsible for transporting oxygen.
The different blood groups arise as a consequence of mutations in the DNA of the genes that encode them, which implies that they are inherited characteristics. The most frequently identified mutation is the change of a single nucleotide of DNA, which in scientific jargon is known as SNPs. Most blood groups arise from one or more SNPs, which either cause the substitution of an amino acid in the protein or result in an incomplete protein.
In other cases, what occurs are losses (deletions) of complete genes. The most important example are Rh negative individuals who lack the D antigen due to a deletion of the gene that encodes it.
The interesting thing about blood groups is that they behave like antigens, the same as the proteins of the viruses and bacteria that infect us. This implies that they have the ability to trigger an immune response and the production of antibodies when they are introduced into an individual who lacks them, either by blood transfusion or by pregnancy. This causes, respectively, post-transfusion hemolytic reactions and hemolytic disease of the fetus and newborn. In the laboratory we detect this antigen-antibody binding through agglutination reactions.
Discovery of the ABO system
The first blood groups were discovered in 1901 by Karl Landsteiner, who described the agglutination reactions that occurred when red blood cells were joined with the plasma of different people. He divided them into 3 groups: group A, group B and group C (currently group O). Landsteiner deduced that the red blood cells had antigens in their membrane that reacted with antibodies that were presented by individuals who lacked them.
The clinical significance of the ABO system lies in the fact that all individuals present in our plasma antibodies against the antigens that we lack. For this reason, if ABO incompatible red blood cells are transfused, a hemolytic reaction occurs that can become very serious and even end the life of the patient.
This differentiates them from the rest of the clinically significant erythrocyte antibodies, which are of immune origin and are not produced until there is contact with the antigen, either by transfusion or during pregnancy.
More than three hundred blood groups
After the discovery of the ABO system, other blood groups were identified as a consequence of different pathological events produced by erythrocyte antibodies, both due to hemolytic disease of the fetus and newborn (anti-D, anti-K and anti-Jka) and due to reactions Hemolytic transfusion (anti-c, anti-e, and anti-Fya). A summary of the antigenic systems with the most clinical significance is shown in the following table.
Until the 1950s, blood groups were defined solely by agglutination reactions. Between 1950 and 1970, the structure and biosynthesis of carbohydrates and proteins of the different erythrocyte antigens began to be described. And later, from the nineties, the genes that encode the ABO, Rh systems and, later, the rest of the blood groups were identified. That they are not few.
According to the latest report of the “International Society of Blood Transfusion” of the year 2018, more than 350 erythrocyte antigens have been described. Most of them have been grouped into 36 systems, for sharing characteristics and for having a closely related inheritance.
Sistema Rh “Rhesus”
The most important system after ABO is Rh. Although there are more than 50 antigens within this system, the RhD antigen stands out above all, which is what differentiates Rh positive from Rh negative individuals who lack this antigen. Its importance is explained in two brush strokes: it has an enormous immunogenic capacity, and it is implicated in hemolytic disease of the fetus and newborn as well as in post-transfusion hemolytic reactions.
Its identification not a century ago. It all started in 1939, when Levine and Stetson investigated the hemolytic reaction in a woman transfused with red blood cells from her husband after giving birth to a stillborn child. They detected an antibody in the woman’s plasma that produced agglutination of her husband’s red blood cells and 80% of ABO-compatible red blood cells, concluded that this antibody was independent of those previously described and suggested that the woman had become sensitized. during pregnancy by an antigen, present in the child’s red blood cells, inherited from the father.
A year later, Landsteiner and Wiener discovered an antibody with similar characteristics, obtained after injecting Rhesus macaque red blood cells into rabbits. They thought it was the same antibody and that’s why they named it Rh. Later it was found that they were different antibodies but this denomination was maintained.
Beyond AB0 and Rh
In 1946, Dr. Coombs described a new antibody in a woman who had given birth to a newborn with hemolytic disease. This new antibody reacted with the red blood cells of the husband and two of their children, in addition to reacting with 7% of the red blood cells of the donors. It was called anti-Kell, after that first patient in whom it was described, Mrs. Kelleher.
Subsequently, new antibodies were described, which were also baptized with the name of the patient in which they were detected: anti-Fya (Duffy system) and anti-Jka (Kidd system), both with clinical significance. Other systems were named as the site where they were detected, among them the Bombay group, detected for the first time in that city.
What are blood compatibility tests?
Before performing a blood transfusion, it is imperative to do everything possible to prevent the patient from having a post-transfusion hemolytic reaction. That is the goal of compatibility testing.
Given the clinical significance of the ABO system and the RhD antigen, their determination is mandatory in compatibility tests and in the follow-up of the pregnant woman. But in addition to looking for compatible ABO and RhD group red cells, it is essential to rule out the presence of antibodies directed against other erythrocyte group systems. For this, a test known as indirect COOMBS is carried out, which allows the detection of antibodies other than anti-A and / or anti-B, in the plasma of patients.
In case we find a positive indirect COOMBS, the specificity of the antibody should be detected, and red cells lacking that antigen should be looked for. If it is a pregnant woman, it is important to follow-up to rule out hemolytic disease in the fetus.
The “rare” blood groups
There are certain individuals whose red blood cells lack an antigen present in almost the entire population (known as a high incidence antigen). This implies that, if they develop an antibody, through contact with foreign blood, it will be extremely difficult to find a compatible blood donor.
This is the case of the extremely rare individuals of the so-called Bombay group, who lack the antigens of the ABO system, including that of the group O individuals. They produce an antibody naturally that makes all red blood cells incompatible except those that they are like them.
Peculiar is also what happens with the Duffy system. This system is found in the receptor for Plasmodium vivax , one of the parasites that causes malaria. This implies that lacking it provides us with an important survival advantage if we live in areas where this disease is endemic. This evolutionary advantage has resulted in more than 60% of black individuals lacking this receptor. The problem for these individuals arises when they have to be transfused in our environment, and they develop antibodies against these antigens, present in practically the entire Caucasian population.
In these specific patients, it is recommended to resort to autotransfusions, keeping red blood cells frozen. There is also a national and international donor panel with rare groups who are advised to donate should there be a need.
María José Candela García is an honorary collaborating professor at the University of Murcia
This article was originally published on The Conversation. Read the original.
