A New Pathway to Universal Donor Blood

The effort to generate universal donor blood has made a significant step ahead. Researchers at DTU and Lund University identified enzymes that, when combined with red blood cells, could eliminate particular sugars found in the A and B antigens of the human ABO blood types. The findings are reported in the scientific journal Nature Microbiology.

For the first time, the new enzyme cocktails not only remove the well-described A and B antigens but also extended variants previously not recognized as problematic for transfusion safety. We are close to being able to produce universal blood from group B donors, while there is still work to be done to convert the more complex group A blood. Our focus is now to investigate in detail if there are additional obstacles and how we can improve our enzymes to reach the ultimate goal of universal blood production.”

Maher Abou Hachem, Study Leader and Professor, Technical University of Denmark

He stated that the finding was made by merging the knowledge of DTU researchers in enzymes from the human gut microbiota with Lund University researchers in carbohydrate-based blood groups and transfusion medicine.

High Demand for Donor Blood

Human red blood cells contain distinct complex sugar structures (antigens) that distinguish the four ABO blood groups: A, B, AB, and O. These antigens ensure donor-recipient compatibility for safe blood transfusions and organ transplants. Donor blood is tested for disease indicators and major blood types. It can then be kept refrigerated for up to 42 days.

The elderly make up a larger portion of the population, and more patients undergo blood-intensive medical operations, resulting in a high need for donor blood. Successfully converting A or B blood types to ABO universal donor blood can significantly minimize the logistics and expenses associated with holding four separate blood types.

Furthermore, the creation of universal donor blood will enhance the supply of donor blood by minimizing the waste of blood that is nearing the end of its shelf life.

The removal of A and B antigens to make universal donor blood is required because they can induce life-threatening immune reactions when transfused into non-matched recipients.

The idea of utilizing enzymes to create universal donor blood was first proposed more than 40 years ago. Since then, more efficient enzymes for removing A and B antigens have been identified, but researchers are still unable to explain or eliminate all blood-related immune reactions, consequently these enzymes are not employed in clinical practice.

Enzymes from the Gut

The DTU and Lund University research groups have developed novel strategies for identifying enzymes that are capable of eliminating the sugars that obstruct the A and B blood antigens.

The study teams isolated novel enzyme combinations from the human gut bacteria Akkermansia muciniphila, which feeds on the mucus that coats the gut’s surface. Given that the complex sugars on the surface of the intestinal mucosa and blood cells have similar chemical compositions, it turns out that these enzymes are incredibly effective.

Hachem added, “What is special about the mucosa is that bacteria, which are able to live on this material, often have tailor-made enzymes to break down mucosal sugar structures, which include blood group ABO antigens. This hypothesis turned out to be correct.

The researchers in this study evaluated 24 enzymes and processed hundreds of blood samples.

Universal blood will create a more efficient utilization of donor blood, and also avoid giving ABO-mismatched transfusions by mistake, 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 safe blood products, while at the same time minimizing blood waste.

Martin L. Olsson, Study Leader and Professor, Lund University

The researchers from DTU and Lund University have submitted for a patent on the novel enzymes and the enzyme treatment approach, and they aim to make additional progress on this in their new collaborative project over the next three and half years.

If successful, the concept needs to be validated in controlled patient studies before being considered for commercial manufacturing and clinical application.

Source:
Journal reference:

Jensen, M., et al. (2024) Akkermansia muciniphila exoglycosidases target extended blood group antigens to generate ABO-universal blood. Nature Microbiology. doi.org/10.1038/s41564-024-01663-4

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