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Researchers have identified a cocktail of enzymes produced by a bacteria in the intestinal microbiota capable of eliminating blood group A and B antigens and thus producing universal blood. The enzymes would also act on their variants recently recognized as determining for the safety of blood transfusions. Although the results are still preliminary, the approach could significantly improve access to universal blood donations.
In humans, the four blood groups are determined by specific antigens (ABO A, B, AB and O) present on the surface of red blood cells. Recently, variants with specific carbohydrate extensions have also been identified. Compatibility between donors and recipients for blood transfusions and organ donations depends on these antigens. If the blood types do not match, it triggers a potentially fatal immune response in the recipient.
In order to anticipate needs, each blood donation is analyzed by laboratories to identify these antigens, as well as possible pathological markers and traces of toxins. However, there is currently a global shortage of donor blood due to the world’s aging population and increasing demand — not to mention that blood bags only last for a maximum of 42 days.
To remedy this, research is focusing on the enzymatic conversion of A and B antigens to group O. Group O only expresses the precursor antigens of A and B (H antigens) and can thus be a universal donor. Converting these two blood groups would significantly reduce the costs and logistics of collecting and storing donated blood from four different groups. Additionally, increasing universal blood donations would reduce waste related to incompatibilities.
“ When we can create universal ABO blood, we will simplify the logistics of transporting and administering safe blood products, while minimizing blood waste. », Explains in a press release from the Technical University of Denmark (DTU), Martin L. Olsson, of Lund University in Sweden.
In this vision, different enzymes have been identified to efficiently eliminate A and B antigens. Indeed, the enzymatic conversion of blood antigens was proposed more than 40 years ago. However, unexplained incompatibility issues persist, hindering their clinical application. Olsson and his colleagues at DTU propose a new enzyme cocktail that could finally overcome these obstacles.
Soon universal group B donors?
To identify new enzymes that could target the A and B antigens, the researchers in the new study focused on those produced byAkkermansia muciniphila. This is a bacteria naturally present in our intestinal microbiota and which feeds on the complex carbohydrate molecules present in the intestinal mucosa. These molecules include compounds whose structure is closely similar to that of the A and B antigens on the surface of red blood cells. The researchers then hypothesized that the bacteria’s enzymes could also degrade them.
“ The particularity of the mucous membrane is that the bacteria capable of living there often have enzymes specially designed to degrade the carbohydrate molecules of the mucus it secretes, among which are the antigens of the ABO blood group.
“, explains Maher Abou Hachem of DTU, who co-led the study — published in the journal Nature Microbiology. Recent separate research suggests thatA. muciniphila is involved in extramedullary hematopoiesis, a mechanism aimed at compensating for insufficient blood cell production.
ABO blood group antigens found on the surface of red blood cells are also found on the mucous layer that lines the surface of the intestine. Researchers harnessed specialized human gut bacteria and its ability to use these antigens as nutrients to discover and develop two enzyme blends that convert group A and B red blood cells into universal donor blood. © Mathias Jensen/ DTU
To test their hypothesis, the researchers tested 24 different enzymes produced by the bacteria to process hundreds of blood samples. Unlike previous studies, the trials were carried out under mild conditions and without additives to stimulate enzyme activity — which improves clinical viability.
They thus found that two mixtures of enzymes were particularly effective in degrading not only the conventional A and B antigens, but also the recently described extended variants — a first for this type of process. According to the team’s estimates, approximately 18 and 8 mg of enzymes are sufficient to convert one unit (approximately 200 ml) of red blood cells A and B (respectively).
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“ For the first time, the new enzyme cocktails eliminate not only the A and B antigens, but also most of the expanded variants that were previously not recognized as problematic for blood safety », Indicates Abou Hachem.
However, while the results suggest it may soon be possible to produce universal blood from group B donors, more research is needed for group A conversion, which is more complex, the experts said. Furthermore, the present study does not report possible interactions of enzymes with the Rhesus factor, which is also determining for the safety of transfusions.
Nonetheless, the researchers plan to further explore possible obstacles over the next three years, before moving into clinical trials. A patent application has already been filed for their enzyme cocktail and treatment protocol. “ Our goal now is to study in detail whether there are other obstacles and how we can improve our enzymes to achieve the ultimate goal of universal blood production. », concludes Abou Hachem.
