An era has opened in which organ transplantation can be performed even with different blood types. A technology has been developed to change the blood type of a transplant organ to type O so that it can be transplanted regardless of the patient’s blood type. The organ that the Canadian research team succeeded in this time is the kidney. A kidney donated by a donor has been replaced with a common kidney that is suitable for patients with all blood types. This technology, which does not have rejection reactions, is likely to be applied to other organs as well.
Removal of blood type B antigen to make type O
Even at this moment, there are many people eagerly waiting for organs for transplantation. This is because donors are limited and each person has a different organ that is suitable for them. When an organ is provided, doctors first check whether the size of the organ and the patient are correct, and whether the blood type is appropriate. If the blood types do not match, immune rejection occurs, making transplantation impossible.
Blood type is determined by ‘antigens’, sugar molecules on the surface of red blood cells in the blood. For example, if you have A antigen, you are classified as type A, and if you have antigen B, you are classified as type B. Blood type AB has both antigens. The absence of both antigens results in type O. A and B antigens may also be present on the surface of blood vessels in organs.
However, there are also ‘antibodies’ that recognize and attack these antigens in the plasma constituting the blood. Type A has B antibodies and type B has A antibodies. Antigen-free type O has both antibody A and antibody B, and type AB has no antibody.
The problem is that when organs of different blood types are transplanted, the antibody in the patient’s immune system regards the organs as foreign invaders and initiates an attack, resulting in immune rejection. For example, when a type A donor organ is transplanted into a type B recipient, the B antibody recognizes the type A antigen on the surface of the red blood cells as a foreign substance and causes hemolysis, which destroys the red blood cells.
On the other hand, antigen-free type O does not cause antigen-antibody reaction, so it is the only ABO blood type that can be transplanted into another blood type. This is the reason for injecting type O blood, so-called ‘general blood’, even when urgent blood transfusion is needed. On the other hand, type O blood type does not accept organs from either type A or B, so only type O organs must receive organs. As such, type O individuals take longer to wait until they find a suitable organ.
Immune rejection is the most important factor in determining the success or failure of an organ transplant. However, recently, a research team at the University of Montreal, Canada, has developed a technology to completely solve this problem. It is a method that converts all donor kidneys to type O. Kidney transplantation is recognized as the optimal treatment for end-stage renal failure patients. End-stage renal failure refers to a disease in which the function of the kidneys is lost and requires treatment to replace the role of the kidneys. It is a disease that is often accompanied by serious complications such as cardiovascular disease, which can seriously threaten human life. However, a shortage of donors prevents many patients from getting a kidney transplant. In Korea, as of 2019, the number of people waiting to receive a kidney transplant from a brain-dead person reached 24,786.
The research team conducted an experiment on three blood type B kidneys that were judged not to be transplanted. An enzyme called α-galactosidase was used to convert type B kidney to type O blood. This enzyme is responsible for breaking down sugar (glycoprotein) in the human intestine. The technology to convert universally transfusionable type O blood using enzymes in the intestine was devised by a team led by Professor Stephen Withers at the University of British Columbia in Canada and published in the international academic journal Nature Microbiology in 2018. The research team got the idea here.
In order to transplant blood-matched kidneys into all patients, it is essential to effectively remove antigens prior to transplantation. After immersing three type B blood type kidneys in a customized chemical mixture for 5 hours, the research team injected alpha-galactosidase into the renal blood vessels using a normal body temperature perfusion machine (NPM). Then, within a few hours, the antigens in the blood vessels were removed. As the antigen disappeared, all three kidneys, which were blood type B, became type O. The research results of the research team were published in the international scientific journal ‘General Surgery’.
Long waiting time Type O is the longest
This isn’t the first time the blood type of a human organ has been changed. In February, a team led by Professor Marcelo Sippel of the Department of Surgery at the University of Toronto in Canada succeeded in an experiment to convert the lungs of a blood type A donor into type O using an enzyme in the human intestine. When an enzyme that degrades glycoproteins was injected into the lungs, 97% of antigen A was removed within 4 hours. As a result of operating the lungs of type O blood type created in this way by computer simulation, immune rejection did not appear. On the other hand, the lungs that were not treated with the enzyme showed a rejection reaction to the type O blood group and died. The research results of the research team were published in the international scientific journal ‘Science Translational Medicine’.
The National Organ System and Blood Management (KONOS) publishes statistical data on the status of domestic organ transplantation every year. It was also published in June, and according to this, as of 2020, there were 12,296 people with type A, 9,690 people with type B, 1554 people with type O, and 3817 people with type AB. There were 793 cases of type B, 1528 cases of type O, and 306 cases of type AB. There is a shortage of donated organs compared to the number of people on the waiting list for any blood type organ.
Long-term waiting times also vary widely by blood type. Usually, the waiting time for a lung transplant in type O patients is twice that of type A patients on average. Even in the case of kidney transplantation, the waiting time for type A or type AB patients is 2 to 3 years, whereas for type O or B type patients, the average waiting time is 4 to 5 years. As with blood transfusion, type A and B patients can receive not only type O organs but the same blood type, but type O patients can only receive type O organs. Experts say that type O patients who need a lung transplant have a 20% higher risk of dying while waiting for a suitable organ than other blood types.
The medical community expects that the technology to convert the kidneys and lungs to type O blood will be able to alleviate not only organ shortages but also blood shortages. The goal of the University of Montreal research team is to commercialize the technology. To this end, the research team plans to conduct clinical trials of enzyme-treated kidneys in humans. If this clinical trial is successful, it might completely eliminate the blood-type barrier by converting all organs to type O. This is because the number of general-purpose organs that depended only on type O is dramatically increasing.
Creating a universal type O organ that can be transplanted into all blood types means that it can save more lives and reduce organ waste by first transplanting an organ to a medically urgent patient. It is hoped that this will be verified as soon as possible so that it can be applied to other organs as well.
