Kidneys with group zero
Scientists have changed the blood type of the donor kidney
Denis Yatsutko, XX2 century
Researchers from the University of Cambridge have experimentally confirmed that blood group antigens can be removed from human kidneys. It is assumed that in this way the limited compatibility of donor organs will be overcome, which as a result will provide more people in need of transplantation.
Blood type is an essential factor in the compatibility of donor organs and the recipient's body. It is impossible for a person with group A(II) blood to transplant a kidney from a person with group B(III) blood: the immune system will react to alien antigens, and rejection will occur. The same applies to the transfusion of blood itself. Therefore, in ideal conditions, when there is time and a choice from a sufficient number of donors is possible, transplantation (including blood transfusion) is best performed between a donor and a recipient with the same blood groups.
Note that, if we approach the issue strictly, then people have a lot of blood groups. They are determined by at least 270 antigens based either on oligosaccharide epitopes or on specific amino acid sequences of proteins. Plus, there are about forty blood antigens that are not assigned to any group in any system (by the way, there are more than forty blood group systems). Most antigens are integrated into the cell membrane, but some are adsorbed on the surface of red blood cells. At the same time, there are about a million of them on the surface of each erythrocyte. Fortunately, in many cases, only carbohydrate antigens AB0, which determine blood groups 0, A, B and AB (in the usual designations, respectively: I, II, III and IV), have clinical significance during transplantation.
In extreme cases, if there is no donor with a suitable blood type, transplantation from donors with groups A and B to recipients with group AB is allowed, and from donors with group 0 to anyone. In this sense, both the actual blood and the "solid" donor organs of people with blood group 0(I) are the most universal. However, they are not always available at the right time.
However, back in the early 1980s, scientists started talking about the possibility of converting the blood of groups A, B and AB into the blood of the universal group 0 with the help of enzymes. Soon the tests began. First, alpha-galactosidase extracted from coffee beans was used for this. Red blood cells of group B, converted by this enzyme into red blood cells of group 0, normally survived in all recipients, regardless of blood type.
Gradually, from experiments with single erythrocytes, they switched to full-fledged transfusions, tried new enzymes. In 2000, the journal Transfusion published a publication about the successful transfusion of enzymatically converted from B to 0-type blood to 21 people. At first, it was more difficult with the transformation of the blood of groups A and AB: it was not possible to find quite suitable enzymes.
The turning point happened in 2007 — a publication was published, the authors of which, having scanned a library of about 2500 bacterial and fungal lysates, identified, studied and described a whole family of enzymes that actively cleave B-antigen, found a bacterial enzyme for cleaving A-antigen and managed, by combining different enzymes, to reliably convert to 0-type red blood cells of type AB.
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Today, the enzymatic conversion of blood to type 0 is already more or less common. However, people sometimes have to not only transfuse blood, but also transplant donor organs. There are also AB0 antigens on the walls of the vessels penetrating them. And, as mentioned above, an organ from a donor with a suitable blood type for the patient is not always available. Therefore, the current topic of biomedical research is the enzymatic removal of blood group antigens from "solid" organs. This is the subject of a recent study by Cambridge scientists, the results of which are published in the British Journal of Surgery (MacMillan et al., O004 Blood group antigen removal of a human kidney using ex-vivo normothermic machine perfusion technology). Professor of transplantology Mike Nicholson and graduate student Serena MacMillan came up with the idea to pump a solution of cell-free perfusate saturated with alpha-galactosidase obtained from fragilis bacteroids through the kidneys from donors with blood group B (Latin Bacteroides fragilis). For pumping, a normothermal perfusion device was used, a device that connects to a donor organ and passes oxygen-saturated blood or specially developed solutions (perfusates) through it in order to better preserve it for later use. Pumping lasted six hours. A thorough examination of the tissues of the kidneys treated in this way showed a decrease in the number of B-antigens to almost zero. Theoretically, this means that a donor kidney subjected to such a procedure becomes universal — it can be transplanted to a recipient with any blood type.
In practice, of course, before proceeding to human trials, scientists will also have to check how a kidney with enzymatically removed antigens will react to its supply of normal blood of groups A and/or 0. It is assumed that scientists will also check this with the help of a normothermal perfusion apparatus.
If the trials are eventually completed successfully and lead to the introduction of the method into clinical practice, this, in the future, will mean for many patients a reduction in the waiting time for a suitable donor kidney at times.
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