universal red blood cells within reach
An international team of academic and industry scientists has come up with a feasible way of making universal red blood cells that are stripped of their blood type. The hope is that it can be developed into a viable way of relieving blood bank shortages.
There are four human blood groups: A, B, AB and O, each with a different combination of antigens on the surface of each blood cell. Antigens provoke immune systems into creating antibodies that bind to them.
If a person receives blood of a type that is not compatible with their own, there is a risk their immune system will attack it, destroying the red blood cells, producing kidney failure, and the person could die.
Compatibility of blood group is a bit complicated and depends on who is giving and who is receiving.
A person with blood group AB has both A and B antigens on the surface of their red blood cells, and they do not have antibodies against either A or B antigen, so they can receive blood from any group but can only give blood to a person with blood group AB.
Blood group A people have antigen type A on the surface of their red blood cells and have antibodies against type B antigen. So a type A person can have blood from people of type A (preferred) or O and can give blood to people of type A or AB.
A person with blood group B has the B antigen on the surface of their red blood cells and antibodies against type A antigen. So a type B person can have blood from type B (preferred) or O people and can give blood to people of blood type B or AB.
People with blood type O have neither A nor B antigens on the surface of their red blood cells, but they have high levels of antibodies against type A and type B antigens. So a type O person can only have blood from another type O person, but they can can give blood to people with blood types A, B, AB or O.
When a person with blood type A, B or AB needs a blood transfusion the first priority is to match their blood type. If there is not enough time and their type is not available and type O is, then they are given type O.
The wrong blood is given by mistake about once in every 15,000 transfusions and blood banks sometimes have shortages of one type of blood.
The idea of “universal red blood cells” has been around for some time and its feasibility has been demonstrated in clinical trials. But so far the process proved to be impractical.
In the new study, a team of scientists led by Professor Henrik Clausen from the University of Copenhagen in Denmark, found a more abundant source of glycosidase enzymes in bacteria. They found two bacterial glycosidase gene families with enzymes that efficiently remove A and B antigens from red blood cells (RBCs).
Prof Clausen and colleagues conclude that “The enzymatic conversion processes we describe hold promise for achieving the goal of producing universal RBCs, which would improve the blood supply while enhancing the safety of clinical transfusions”.
The university scientists worked with US industry scientists from ZymeQuest in Beverly, Massachusetts. The next step is to start clinical trials to test the method’s treatment safety and efficiency.
Published online: 1 April 2007; | doi:10.1038/nbt1298
Bacterial glycosidases for the production of universal red blood cells
1 ZymeQuest Inc., 100 Cummings Center, Suite 436H, Beverly, Massachusetts 01915, USA.
2 Architecture et Fonction des Macromolécules Biologiques, UMR6098, CNRS, Universités Aix-Marseille I & II, Case 932, 163 Avenue de Luminy, 13288 Marseille Cedex 9, France.
3 Departments of Cellular and Molecular Medicine and Oral Diagnostics, University of Copenhagen, Blegdamsvej, DK-2200 Copenhagen N, Denmark.
4 Department of Chemistry, University of New Hampshire, Durham, New Hampshire 03824, USA.
5 Harvard Microchemistry and Proteomics Analysis Facility, Harvard University, Cambridge, Massachusetts 02138, USA.
6 Division of Hematology and Transfusion Medicine, Department of Laboratory Medicine, Lund University and University Hospital Blood Center, SE-22185, Lund, Sweden.
7 Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215, USA.
8 Hematology Division Brigham & Women’s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
9 These authors contributed equally to this work.
Enzymatic removal of blood group ABO antigens to develop universal red blood cells (RBCs) was a pioneering vision originally proposed more than 25 years ago. Although the feasibility of this approach was demonstrated in clinical trials for group B RBCs, a major obstacle in translating this technology to clinical practice has been the lack of efficient glycosidase enzymes. Here we report two bacterial glycosidase gene families that provide enzymes capable of efficient removal of A and B antigens at neutral pH with low consumption of recombinant enzymes. The crystal structure of a member of the -N-acetylgalactosaminidase family reveals an unusual catalytic mechanism involving NAD+. The enzymatic conversion processes we describe hold promise for achieving the goal of producing universal RBCs, which would improve the blood supply while enhancing the safety of clinical transfusions.