Scientists developing universal donor blood to address global blood shortages

In a groundbreaking development, researchers from DTU and Lund University have uncovered enzymes capable of stripping specific sugars from red blood cells, a crucial step towards the creation of universal donor blood. The discovery, detailed in the esteemed scientific journal Nature Microbiology, marks a significant leap forward in transfusion medicine.

Professor Maher Abou Hachem, leading the study at DTU, highlights the novelty of their findings: "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."

This breakthrough, achieved through a collaboration between DTU's expertise in gut microbiota enzymes and Lund University's proficiency in blood group research, holds promise for revolutionizing blood transfusion practices.

The urgency for such advancements stems from the soaring demand for donor blood, driven by an aging population and an increase in blood-intensive medical procedures.

The demand for blood transfusions is steadily rising due to an aging population and increasing reliance on blood-intensive procedures. Developing universal blood offers a multitude of benefits:

Currently, blood transfusion relies on matching the donor's and recipient's blood types to ensure compatibility. However, this process is complicated by the presence of A and B antigens, which can trigger life-threatening immune reactions if not matched correctly.

ABO blood type mismatches can lead to various issues, particularly in medical procedures such as blood transfusions and organ transplants. Here are some potential problems patients may face:

Acute Hemolytic Transfusion Reaction (AHTR): When a patient receives blood from a donor with a different ABO blood type, their immune system may attack the transfused red blood cells, leading to a severe and potentially life-threatening reaction known as AHTR.

Delayed Hemolytic Transfusion Reaction (DHTR): This occurs when there is a delayed immune response to transfused blood, resulting in the destruction of donor red blood cells. DHTR typically manifests days to weeks after transfusion and can cause anemia and jaundice.

Transfusion-Related Acute Lung Injury (TRALI): In ABO-incompatible transfusions, white blood cell antibodies present in the donor blood can cause a severe reaction in the recipient's lungs, leading to acute respiratory distress.

Organ Transplant Rejection: ABO blood type incompatibility between the donor and recipient in organ transplantation can trigger an immune response, leading to rejection of the transplanted organ. This occurs because ABO antigens are also expressed on the surface of various tissues and organs.

Hyperacute Rejection: In organ transplantation, if the donor organ's blood type is incompatible with the recipient's blood type, hyperacute rejection can occur almost immediately after transplantation. This rapid rejection is due to preformed antibodies in the recipient's blood attacking the donor organ.

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Challenges in Finding Compatible Donors: A patient with a rare blood type may face difficulties in finding a compatible blood donor for transfusion or organ transplantation, which can delay necessary medical treatments.

Increased Risk of Complications: ABO-incompatible transfusions or transplants can lead to complications such as infection, organ failure, and even death if not managed promptly and appropriately.

To address this challenge, researchers have long explored the use of enzymes to modify blood cells and render them universally compatible. Despite decades of research, existing enzymes have fallen short of clinical application due to their inability to eliminate all immune reactions. However, the newly discovered enzymes, sourced from the gut bacterium Akkermansia muciniphila, demonstrate unprecedented efficiency in removing blood group antigens.

"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 AB0 antigens. This hypothesis turned out to be correct," explains Maher Abou Hachem.

The research teams meticulously tested 24 enzymes on hundreds of blood samples, paving the way for the development of a more streamlined and cost-effective blood transfusion process. Professor Martin L. Olsson, leading the study at Lund University, emphasizes the potential impact of universal donor blood: "Universal blood will create a more efficient utilization of donor blood, and also avoid giving AB0-mismatched transfusions by mistake, which can otherwise lead to potentially fatal consequences in the recipient."

The implications of this discovery extend beyond medical efficacy to logistical and economic benefits. Converting A or B blood types into universal donor blood can significantly reduce the complexities associated with storing multiple blood types and minimize wastage by extending the shelf life of blood products.

While the prospect of universal donor blood holds immense promise, researchers caution that further refinement and testing are necessary before clinical implementation. The teams have applied for a patent on the new enzymes and are embarking on a new joint project funded by various research organizations to advance their research over the next three and a half years.

The next crucial step involves clinical trials to evaluate the safety and efficacy of this approach in human patients. If successful, this discovery could revolutionize blood transfusion practices, ensuring a safer and more efficient blood supply for patients worldwide.

Funding for the initial research project was provided by the Independent Research Fund Denmark (Technology and Production Sciences, FTP), the Swedish Research Council, ALF grants from the Swedish government and county councils, as well as the Knut and Alice Wallenberg Foundation and Research Fund Denmark, Natural Sciences (FNU). The continuation of this research is supported by the Novo Nordisk Foundation, Interdisciplinary Synergy Programme.

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