Up until now, before an organ transplant, it has to be ensured that the blood groups of donor and recipient match one another. Depending on their blood group, some people therefore have poorer chances of getting a life-saving organ. In a feasibility study, researchers have now shown that specific enzymes can be used to remove blood group characteristics from donor lungs. This could make the organs universally transplantable.
Our red blood cells have certain structures on their surface that determine the blood group: In the ABO system of blood groups, this is the A antigen for blood group A, the B antigen for blood group B, both for AB and none for 0. Our immune system forms antibodies against antigens that we do not have ourselves. Contact with foreign antigens – for example through a blood transfusion – leads to a life-threatening immune reaction in which the blood clots. Therefore, we can only receive blood from donors who have the same blood type as us, or universal blood type O. The same applies to organ donation: organs from donors with mismatched blood types are rejected by the recipient’s body.
From blood group A to blood group 0
In practice, this means that some patients, depending on their blood group, have to wait an above-average length of time for a donor organ. Patients with blood group O, who can only receive organs from donors who also have blood group O, wait on average twice as long for a lung transplant as patients with blood group A. “This has an impact on mortality. Type 0 patients who need a lung transplant have a 20 percent higher risk of dying while waiting for a match,” says Aizhou Wang of the Toronto General Hospital Research Institute in Canada. In addition, some organs are wasted because, despite long waiting lists, a suitable recipient cannot be found in time.
Together with her team, she therefore worked on a solution to this problem: “We examined the safety and preclinical effectiveness of two enzymes that have been shown to be able to remove the A antigen,” the researchers report. This should make it possible to transform organs from blood group A into organs from blood group 0, which are suitable for all recipients. “Having universal organs means we could remove the blood match barrier and prioritize patients based on medical urgency, saving more lives and wasting fewer organs,” says Wang’s colleague Marcelo Cypel.
Donor lungs in artificial circulation
For their study, the researchers used eight blood type A human donor lungs that were unsuitable for transplantation. They connected this to a so-called Ex Vivo Lung Perfusion (ECLP) system, which supplies the organ with nutrients outside the body. In this way, the artificial circulatory system replaces the lack of blood flow and allows the organs to be kept at body temperature without damage.
They then treated one of the donor’s two lungs with a combination of two enzymes, FpGalNAc deacetylase and Fpgalactosaminidase, which were originally discovered in the human intestine. Previous experiments had already suggested that these enzymes are able to remove the A antigens on cells by breaking down the sugar molecules they contain. And indeed: after a treatment period of four hours, the enzymes in the treated lungs had removed 97 percent of the A antigens and thus converted the organs to blood group 0. The other lung of each donor remained untreated and served as a control.
Simulated transplant successful
Now the researchers simulated a transplant for both lungs. To do this, they added blood containing anti-A antibodies to the artificial circuit. As expected, a rejection reaction against the untreated lung showed up – just like when a lung is transplanted from a blood group A donor into a blood group O recipient. However, the lungs treated with the enzymes were well tolerated. There was no rejection reaction, nor were there negative effects of the enzyme treatment on organ function.
“The treatment described here could expand the pool of universal donor organs from the current 55 percent (blood type O donors) to over 80 percent including modified A organs,” the authors write. “As a result, this strategy can significantly improve access and fairness in organ donation.” As the next steps towards this goal, the researchers want to use mice to investigate how organs with modified blood groups behave in living organisms. If these trials are also successful, they plan to conduct a clinical trial in human patients.
Source: Aizhou Wang (Toronto General Hospital Research Institute, Canada) et al., Science Translational Medicine, doi: 10.1126/scitranslmed.abm7190