Lungs without antigens

Transplantologists changed the blood type of donor lungs

Anastasia Kuznetsova-Fantoni, N+1

Canadian scientists have found a way to turn donor lungs into a universal transplant. They used a bacterial enzyme that cuts off the antigens of the AB0 system on the surface of endothelial cells, making the organ suitable for transplantation to any person. In the study, scientists were able to successfully clear the donor lungs of A-antigen by 97 percent, so in the future they plan to start preclinical trials for transplanting such organs. The work is published in Science Translational Medicine (Wang et al., Ex vivo enzymatic treatment converts blood type A donor lungs into universal blood type lungs).

Finding donor organs for transplantation is a very difficult task. And it's not just that there are not enough donors for all patients. Not all organs are suitable for each individual person due to antigenic incompatibility.

Currently, two main antigen systems are used in transplantology: HLA and AB0. The latter are especially important in organs where there are many blood vessels (for example, in the lungs), where AB0 antigens are located on the surface of the endothelium. These antigens are oligosaccharides. The differences between them are in the terminal monosaccharide (D-galactose in group B and N-acetylgalactosamine in people with group A). Theoretically, to turn a person into a universal donor (with blood group 0, that is, without immunogenic monosaccharides on the cell surface), you only need to cut off the end groups on the oligosaccharides.

Canadian scientists recently found enzymes in one of the gut bacteria Flavonifractor plautii, which are able to cut off N-acetylgalactosamine from an oligosaccharide, thus turning group A blood into group 0 blood. These enzymes are called azymes.

Now the same Canadian team of researchers led by Stephen G. Withers from The University of British Columbia has tested an open method of converting blood groups in action. They selected 8 lungs that were unsuitable for transplantation, and then placed them under a dome in which the optimal temperature was maintained, and the lungs received a solution of oxygen and nutrients.

Lungs during perfusion of enzyme solution. A drawing from an article by Wang et al.

This is a standard procedure (ex vivo lung perfusion), which is used in transplantology to assess the function of donor lungs, only this time scientists added enzymes to the perfusion solution. Within four hours — and this is the standard time of ex vivo lung perfusion — the organs lost 97 percent of A-antigen from the walls of the endothelium. It is also important that the doctors did not notice any signs of organ damage.

To test how the lungs will react to the blood plasma of group 0, which contains antibodies against the A-antigen, scientists treated 3 organs with it. The researchers did not find a compliment reaction and inflammatory mediators, and also did not see histological changes in organ tissue, which indicates the absence of an antigen-antibody reaction.

In the future, doctors plan to conduct experiments on transplanting treated lungs to mice in order to assess the viability of such organs. If tests on animals, and subsequently on humans, are successful, then, according to the authors, this will increase the number of universal donor organs (with group 0 according to the AB0 system) from 55 percent to 80 percent.

Canadian transplantologists have proposed to increase the standard storage temperature of donor lungs. They conducted experiments with the lungs of pigs, in which the temperature of 10 degrees Celsius was more favorable for the lungs than the standard temperature of 4 degrees Celsius.

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