Blood group zero from the second
A = 0
Maxim Rousseau, Polit.roo
To cope with the shortage of donated blood, scientists offer different methods. One of the promising directions of their work is to turn the blood of the most common group – the second (A) – into the blood of the first group (0), which can be transfused to patients with other blood groups.
Trying to save the patient's life, doctors have sometimes resorted to blood transfusion for a long time. Sometimes this gave an excellent result, for example, on April 20 (8), 1832, the "civilian general staff doctor" Andrei Martynovich Wolf in St. Petersburg transfused the blood of her husband to a woman in labor who was suffering from blood loss and saved the patient. But in other much more frequent cases, the patient died after transfusion.
The reason for this was found out only in 1900, when Karl Landsteiner discovered human blood groups. At first, three were known, but a fourth was discovered very quickly. They are now known as the AB0 system. In the late 1930s, Landsteiner, then working in the USA, together with his collaborator Alexander Wiener, discovered an independent system of blood groups, now known as the Rh factor. Now more than thirty blood group systems are known, but the most important in practice are AB0 and Rh factor.
Each of them in the blood is a group of molecules (carbohydrates or proteins) represented in the cell wall of human erythrocytes. For example, the AB0 system is determined by the presence in the erythrocyte envelope of two molecules belonging to the class of oligosaccharides. On the erythrocytes of people with the second blood group there are molecules of agglutinogen-A, in people with the third blood group – agglutinogen-B, with the fourth – and agglutinogen-A, and agglutinogen-B. Finally, in people with the first blood group, neither of the two agglutinogens is represented on the erythrocyte membrane, so it is denoted by zero. They say that initially Landsteiner designated this group not with zero, but with the letter O from the German word ohne "without", but now everyone is used to zero.
The immune system of each person produces antibodies to those membrane molecules that are not in his body. Accordingly, a person with blood group A in the blood plasma will have antibodies to agglutinogen-B, a person with blood group B – to agglutinogen-A, with group 0 – to both agglutinogens, and with group AB – to none of the two. Having come across foreign substances in the body that they target, antibodies stick together with them (the so-called agglutination reaction), and red blood cells precipitate. It is with the reaction of agglutination that the death of people who received blood from the wrong group during transfusion is associated.
To complete the picture, let us clarify that blood groups A and B can be determined by oligosaccharides, the molecules of which differ slightly. They are designated by digital indexes: A1, A2, A3 ... But these differences do not affect the compatibility of blood groups.
Since people with the AB blood group do not have antibodies to any of the agglutinogens, they can be transfused with blood of any group (provided that the Rh factor and, if necessary, other parameters match). The opposite is not true: if we transfuse blood of group AB to the owner of blood of group A, or B, or 0, then his antibodies will react and an agglutination reaction will begin.
But the blood of group 0 can (again, taking into account the Rh factor) be transfused to carriers of any other group. In the erythrocytes of this group there is neither agglutinogen-A nor agglutinogen-B, which means that the antibodies will not react to anything.
Agglutination reaction when mixing blood of different groups. If the antibodies meet with their agglutinogen, the red blood cells stick together into lumps and precipitate.
It would seem that when the rules of interaction of blood groups are known, there should be no problems with transfusion, you just need to correctly determine the patient's group and use the necessary donor blood. But there is always not enough donor blood. In Russia, one and a half million people need blood transfusions a year. About 16,500 liters of donated blood are used in medical institutions in the United States every day. The demand for donated blood is growing from year to year. "Universal" blood of group 0 is especially in demand in emergency situations when there is no time to determine the patient's blood type.
Although blood type 0 is the most common in the world (about 40% of the population), it is always in short supply. Therefore, the idea has long arisen to turn the blood of the second most common group – A – into the blood of group 0 in order to replenish its reserves. To do this, you need to learn how to remove oligosaccharide molecules from the surface of red blood cells.
It can't be said that this is absolutely fantastic. Doctors know that in some bacterial infections, substances secreted by bacteria change agglutinogen-A1 so that it becomes similar to B so much that the analysis may give an incorrect result. At the same time, it is still impossible to transfuse the blood of group B to the patient, since the antibodies from his blood have not gone anywhere. After recovery, agglutinogen-A1, characteristic of the patient, is restored in the blood. Also, changes in membrane molecules in erythrocytes have been noted in some oncological diseases.
Since this happens in diseases, it is necessary to achieve the same effect by means of medicine. In 2004, an article was published in the specialized journal Transfusion Medicine Reviews, which described two types of experiments. In one case, the enzyme galactosidase acted on red blood cells of group B, splitting off part of the molecular chain of the olisaccharide and converting them into red blood cells of group 0. In the second, the polyethylene glycol molecule did not change the surface molecules of red blood cells, but, joining them, closed them from antibodies. However, animal experiments have shown that such erythrocytes with "masked agglutinogens" have a shorter life span than ordinary ones. In addition, quite often they caused an immune reaction of the body.
In 2007, an international team of researchers led by Henrik Clausen from the University of Copenhagen tried more than two and a half thousand bacterial and fungal enzymes in search of those that will effectively affect the membrane agglutinogens of erythrocytes. Earlier, employees of the biotech company ZymeQuest learned to use an enzyme isolated from coffee beans for this purpose. It removed agglutinogen-B, but it did not work very effectively.
Clausen and his colleagues managed to find two suitable bacterial enzymes from the glycosidase group. The enzyme borrowed from the bacterium Elizabethkingia meningosepticum cleaved agglutinogen-A, and the enzyme bacteria Bacterioides fragilis reacted with agglutinogen-B. As a result, the treated erythrocytes did not differ immunologically. The authors proposed to call such blood "enzymatically converted to group 0 blood" (enzyme converted to O, ECO), and to designate specific cases as A-to-O and B-to-O. Standard tests for determining the blood group gave the desired result – group 0. The results of the work were published in the journal Nature Biotechnology.
However, until now, the bacterial enzymes available to scientists have not worked effectively enough to convert the blood of one group into another so that they can be recommended for widespread use. Perhaps a new study recently published in the journal Nature Microbiology (Rahfeld et al., An enzymatic pathway in the human gut microbiome that converts A to universal O type blood) will be the next step to success.
Canadian scientists from the University of British Columbia, led by Stephen Withers, were looking for the bacteria necessary for the transformation of blood groups among the bacterial population of the human intestine. Many of these bacteria feed on mucins – mucous substances secreted by intestinal epithelial cells. Mucin molecules contain a protein part connected to an oligosaccharide. Therefore, there were reasons to hope that bacteria would have enzymes that cleave the oligosaccharide from the surface molecules of red blood cells.
Scientists isolated bacterial DNA from human faeces and searched for genes responsible for the breakdown of mucins. To do this, they inserted fragments of the found DNA into the genome of the common Escherichia coli coli and looked to see if it would start producing the necessary proteins. They collected a library of 19,500 bacterial genes and eventually found the bacterium Flavonifractor plautii, two enzymes of which, when used together, can turn a group A erythrocyte into a group 0 erythrocyte. According to scientists, these enzymes work in significantly lower concentrations than the enzymes used to transform blood groups in previous studies, which will facilitate their further use.
However, there is still a lot to check before that. For example, it is necessary to make sure that the enzymes found affect only agglutinogens and do not make any changes to other membrane molecules of erythrocytes. It is also necessary to establish how completely agglutinogens are removed in blood samples.
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