Enzyme discovery paves way to develop universal donor blood

Researchers from DTU and Lund University have discovered enzymes that remove obstacles that hindered the development of universal donor blood.

The search for universal donor blood has taken a decisive step forward. Researchers from DTU and Lund University have discovered enzymes that, when mixed with red blood cells, can remove specific sugars that form the A and B antigens in human ABO blood groups. The results have been published in the scientific journal. Nature Microbiology: https://www.nature.com/articles/s41564-024-01663-4

“For the first time, the new enzyme cocktails not only eliminate the well-described A and B antigens, but also expanded variants that were not previously considered problematic for transfusion safety. We are close to being able to produce universal blood from group B donors “Although there is still work to be done to convert the more complex blood to group A, our goal now is to investigate in detail whether there are additional obstacles and how we can improve our enzymes to achieve the ultimate goal of universal blood production,” says the Professor Maher Abou Hachem, leader of the study at DTU and one of the lead scientists behind the discovery.

He claims the discovery is the result of combining the expertise of DTU researchers in human gut microbiota enzymes and Lund University researchers in carbohydrate-based blood groups and transfusion medicine.

High demand for donor blood

Human red blood cells carry specific complex sugar structures (antigens) that define the four ABO blood groups A, B, AB and O. These antigens control the compatibility between donors and recipients for safe blood transfusion and organ transplantation. Donor blood is analyzed for disease markers and major blood groups. It can then be kept refrigerated for up to 42 days.

The need for donor blood is high as the elderly make up a larger proportion of the population and more patients undergo medical procedures that require a lot of blood. Successfully converting blood types A or B to ABO universal donor blood can markedly reduce the logistics and costs currently associated with storing four different blood types. Furthermore, the development of universal donor blood will lead to an increased supply of donor blood by reducing the waste of blood that is approaching its expiration date.

The reason A and B antigens need to be removed to create universal donor blood is because they can trigger life-threatening immune reactions when transfused into unmatched recipients.

The concept of using enzymes to generate universal donor blood was introduced more than 40 years ago. Since then, more effective enzymes have been discovered to eliminate antigens A and B, but researchers still cannot explain or eliminate all blood-related immune reactions and therefore these enzymes are not yet used in practice. clinic.

intestine enzymes

Research groups at DTU and Lund University have been looking for new ways to find enzymes that can remove blood antigens A and B and the sugars that block them. Research teams discovered new mixtures of enzymes from human intestinal bacteria. Akkermansia muciniphila which feeds by breaking down the mucus that covers the surface of the intestine. It turns out that these enzymes are exceptionally efficient, since the complex sugars on the surface of the intestinal mucosa share chemical similarity with those found on the surface of blood cells.

What is special about mucosa is that the bacteria that can live on this material usually have tailor-made enzymes to break down the sugar structures of the mucosa, among which are the ABO blood group antigens. This hypothesis turned out to be correct.”

Professor Maher Abou Hachem, study leader at DTU

The researchers in this study tested 24 enzymes, which they used to process hundreds of blood samples.

“Universal blood will create more efficient utilization of donor blood and will also prevent ABO non-compatible transfusions from being performed in error, which can otherwise lead to potentially fatal consequences in the recipient. When we can create ABO universal donor blood, we will simplify the logistics of transporting and administering blood products safely, while minimizing blood waste,” says Professor Martin L. Olsson, leader of the study at Lund University.

Researchers from DTU and Lund University have applied for a patent for the new enzymes and enzymatic treatment method and hope to continue advancing this new joint project over the next three and a half years. If successful, the concept must be tested in controlled trials with patients before it can be considered for commercial production and clinical use.

The initial research project is funded by the Danish Independent Research Fund (Technology and Production Sciences, FTP), the Swedish Research Council, ALF grants from the Swedish government and provincial councils, as well as the Knut and Alice Wallenberg Foundation and the Danish Research Fund, Natural Sciences, FNU), while the new ongoing project is funded by the Novo Nordisk Foundation, Interdisciplinary Synergy Programme.