by Playfuls Staff |
2nd April 2007
Scientists from Denmark have reported a breakthrough discovery that might solve the problem of incompatibility between blood groups (A, B, AB and O) and might save millions of people annually.[more]
Blood grouping is a complex business, and not all blood groups are compatible. In order to check for compatibility, two cross-matching tests are carried out prior to transfusion - but these tests are based on technology that has not changed since the early days of blood transfusions.
The two most significant blood group systems were discovered during early experiments with blood transfusion: the ABO group in 1901 and the Rhesus group in 1937. The ABO blood group system and the Rhesus blood group system are more likely to cause harmful immunological reactions than the other blood group systems. Blood types are inherited and represent contributions from both parents.
Although blood transfusions can be life-savers in some cases (such as massive blood loss due to trauma or surgery, or in some cases of anaemia and thrombocytopenia), they are also the cause of death in some rare cases of misconduct. In the US, as of 2002, fatal misidentification errors occurred in 1 in 600 000 to 800 000 transfusions while non-fatal errors occurred in 1 in 12 000 to 19 000 cases.
The first concern for the blood center physician is the Acute Hemolytic Transfusion Reaction or HTR, which occurs when incompatible blood is transfused into a patient that should have been given blood of a different blood type. Unfortunately, the reported number of blood misidentification has not dropped, despite the technological advancements. Mismatching of blood causes at least half of all transfusion-related deaths.
However, a team of scientists from the University of Copenhagen, led by cellular biologist Henrik Clausen, seems to have found a “cure” for all these compatibility problems. Their work, reported in the latest edition of Nature Biotechnology, paves the way for a new type of vital liquid, with “universal” red blood cells that can be easily transferred between patients.
According to the abstract of the article, “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 alpha-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.”
What that means is that they’ve uncovered a series of bacterial enzymes that safely “detach” sugar molecules from red blood cells, thus removing the potential danger of an immune reaction to the donated blood. The HTR is mainly caused by the recipient’s reaction to the “foreign” sugar molecules.
When, for example, a type O patient gets A or B blood or when a type A patient gets B blood, unfamiliar molecules on the surface of the foreign blood cells trigger the immune system, which kicks into high gear and throws the patient into shock. The kidneys fail, and the depletion of blood-clotting factors causes bleeding "from the nose, ears--every orifice of the body," according to Mark Popovsky, chief executive officer of the New England Region American Red Cross.
The idea explored by Clausen and his team (which is to use an enzyme to alter the chemistry of the red cell surface) is not new and has been proposed before, in the late 1980s, by Jack Goldstein of the New York Blood Center. Back then, he isolated an enzyme from coffee beans that could convert type B to type O. Clinical trials of the enzyme-produced blood showed it behaved no differently from normal blood in hospitalized patients. Chains of sugars, which cover the cell surfaces of the four human blood types--A, B, AB, and O--all have the same basic sequence, with focus at the end and galactose next in line.
But the enzymes involved were expensive and had to be used under highly acidic conditions that damaged the red cells. Goldstein's team also was not able to find an enzyme that would convert type A to type O.
As a consequence, the development was halted.
However, a company called ZymeQuest in North Andover, Mass., which holds the license to develop Goldstein's technology, had developed since 1997 an automated machine that performed the B-to-O conversion. But effectively converting A cells into O cells proved to be trickier than altering B cells, because about 75 percent of people with type A blood have two kinds of sugar chains on their cells. Out of the million or so structures on each A cell, about 50,000 have a second copy of the final three-sugar sequence, which includes an N-acetylgalactosamine.
Now the same company asked Clausen and his team to search for new enzymes to carry out the A-to-O conversion. Apparently, before reaching the result published in Nature Biotechnology, Clausen’s collaborators put up a tremendous effort to search through more than 2,500 bacteria and fungi in order to finally identify the two most appropriate candidates.
The two enzymes have some important advantages compared to the formerly-used ones: they are more powerful, they work in neutral pH and the room temperature is enough to make them function- a feature which according to Dr. Martin Olsson of Lund University in Sweden is essential. In an hour, they remove all the sugar molecules from the surface of red blood cells, after which they can be easily washed away.
Clinical tests conducted under Olsson’s supervising proved very encouraging, with no adverse reaction reported from test subjects injected with the donors’ blood.
The new method is expected to dramatically reduce problems linked to transportation and availability of the vital liquid. "Those issues could be largely resolved if there were a universally transfusible blood supply," said Doug Clibourn, chief executive of ZymeQuest.
However, despite Clibourn’s optimism, the need for healthy blood donors is still increasing. Despite the promise this technology holds, it doesn't produce a limitless supply of blood. Humans still cannot chemically synthesize molecules that can do everything a red blood cell does.
