It has long been known that blood from different individuals cannot be mixed randomly without the risk of serious consequences, especially within the ABO system which is one of the most important systems to divide blood groups into.
What separates the blood groups are antigens located on the surface of our red blood cells, and which are also found in many other tissues in the body. In our blood plasma there are also naturally-occurring antibodies against the ABO blood group antigens that you do not have yourself.
"And that is the challenge with, for example, blood transfusion and organ transplantation - the wrong ABO group on the blood or organ causes the patient's immune system to react. This leads to the destruction of the blood, which in the worst case can be fatal. That is why you normally cannot cross this so-called ABO barrier," says Martin L Olsson.
He is professor of transfusion medicine at Lund University and senior consultant at Lab Medicine in Region Skåne and together with Maher Abou Hachem, professor of enzyme biotechnology at DTU in Copenhagen, led the study which is now published in Nature Microbiology.
In previous studies, the well-known A and B antigens could be cut out, but recently it has been shown that there are unknown, extended versions of the ABO antigen that our immune response can also react to.
"It is as if we previously felled the big trees in the forest, the known A and B antigens, but did not understand that we also need to clear the undergrowth where the extended antigens are hiding. Now we understand that both parts are required for us to be able to produce a universal blood that works independently of the patient's ABO group," says Martin L Olsson.
The new enzyme cocktail
"We have shown that the principle of a mixture of enzymes works better, but we also see that there is a need for further optimization. Now we understand that even undiscovered ABO extensions need to be eliminated, even though they are not in the textbooks yet. The undergrowth must be carefully examined in the forest of antigens that the red blood cell carries on its surface. The majority of the crossmatch tests are already negative, which is required to be able to transfuse the blood to patients," says Martin L Olsson.
The new enzyme cocktail thus removes for the first time not only the traditional A and B antigens, but also the extended variants, the significance of which was previously completely unknown.
"With this method, we have succeeded in producing universal blood from group B donors with very high accuracy. At the same time, we have taken significant steps towards also being able to convert the more complex group A blood. Our focus is now to carefully investigate whether there are further obstacles and how we can improve our enzymes to reach the ultimate goal: to produce ABO-universal blood," says Maher Abou Hachem, professor of enzyme biotechnology at DTU in Copenhagen.
The researchers have applied for a patent for the enzyme method and now hope to be able to develop it further.
"We are proud to have solved the mystery of why it was not enough to cleave away the ABO groups that we have known since their discovery in 1900. But we are humbled by the challenge of breaking through the ABO barrier, on which all transfusion medicine has been built for more than a century. We still have work to do in formulating the enzyme cocktail in such a way that 100 percent of the treated blood bags can be transfused as universal blood," says Martin L Olsson.
