New blood group identified after 50-year mystery

Scientists identify new blood group after 50-year mystery 

When a pregnant woman had her blood sampled back in 1972, doctors discovered it was mysteriously missing a surface molecule found on all other known red blood cells at the time. The mystery of a blood group has now been cracked after decades. Thousands of lives could be saved around the world after NHS scientists discovered a new blood group system, solving a 50-year-old mystery. The research team, led by NHS Blood and Transplant (NHSBT) scientists in South Gloucestershire and supported by the University of Bristol, found a blood group called MAL. They identified the genetic background of the previously known AnWj blood group antigen, which was discovered in 1972 but unknown until now after this world-first test was developed. Senior research scientist at NHSBT Louise Tilley said the discovery means better care to rare patients can be offered. Ms Tilley, who has worked on the project for 20 years, said it is "quite difficult to a put a number" on how many people will benefit from the test. However, the NHSBT is the last resort for about 400 patients across the world each year. Everyone has proteins outside their red blood cells known as antigens, but a small number might lack them.

"It represents a huge achievement, and the culmination of a long team effort, to finally establish this new blood group system and be able to offer the best care to rare, but important, patients," UK National Health Service hematologist Louise Tilley says, after nearly 20 years of personally researching this bloody quirk. While we're all more familiar with the ABO blood group system and the rhesus factor (that's the plus or minus part), humans actually have many different blood group systems based on the wide variety of cell-surface proteins and sugars which coat our blood cells. Our bodies use these antigen molecules, amongst their other purposes, as identification markers to separate 'self' from potentially harmful not-selves.

Using genetic testing, NHSBT’s International Blood Group Reference Laboratory in Filton have for the first time developed a test that will identify patients missing this antigen. The test could prove a lifesaver for those who would react against a blood transfusion, and will make it easier to find potential blood developers for this rare blood type. Philip Brown, who works at the laboratory, was diagnosed with a form of leukaemia about 20 years ago. He had blood transfusions and a bone marrow transplant, without that, he would have died. "Anything we can do to make our blood much safer and a better match for patients is a definite step in the right direction," he said. Antibodies in our blood plasma detect when a foreign antigen marker is present. If these markers do not match up when receiving a blood transfusion, this life-saving tactic can cause reactions or even end up being fatal. Most major blood groups were identified early in the 20th century. Many discovered since, like the Er blood system first described by researchers in 2022, only impact a small number of people. This is also the case for the new blood group. "The work was difficult because the genetic cases are very rare," explains Tilley.

Previous research found more than 99.9%  of people have the AnWj antigen that was missing from the 1972 patient's blood. This antigen lives on a myelin and lymphocyte protein, leading the researchers to call the newly described system the MAL blood group. When someone has a mutated version of both copies of their MAL genes, they end up with an AnWj-negative blood type, like the pregnant patient. Tilley and team identified three patients with the rare blood type that didn't have this mutation, suggesting that sometimes blood disorders can also cause the antigen to be suppressed. "MAL is a very small protein with some interesting properties which made it difficult to identify and meant we needed to pursue multiple lines of investigation to accumulate the proof we needed to establish this blood group system," explains University of the West of England cell biologist Tim Satchwell. To determine they had the correct gene, after decades of research, the team inserted the normal MAL gene into blood cells that were AnWj-negative. This effectively delivered the AnWj antigen to those cells.

The MAL protein is known to play a vital role in keeping cell membranes stable and aiding in cell transport. What's more, previous research found that the AnWj isn't actually present in newborn babies but appears soon after birth. Interestingly, all the AnWj-negative patients included in the study shared the same mutation. However, no other cell abnormalities or diseases were found to be associated with this mutation. Now the researchers have identified the genetic markers behind the MAL mutation, patients can be tested to see if their negative MAL blood type is inherited or due to suppression, which could be a sign of another underlying medical problem. These rare blood quirks can have devastating impacts on patients, so the more of them we can understand, the more lives can be saved.

The discovery will benefit people around the world, Nicole Thornton said. Head of the laboratory Nicole Thornton said: “Resolving the genetic basis for AnWj has been one of our most challenging projects. “There is so much work that goes into proving that a gene does actually encode a blood group antigen, but it is what we are passionate about, making these discoveries for the benefit of rare patients around the world. Now genotyping tests can be designed to identify genetically AnWj-negative patients and donors. Such tests can be added to the existing genotyping platforms.” Our health reporter Matthew Hill said it was "easy to understate the international significance" of NHSBT in Filton. "Not only have they developed this world-first test, but also they provide countries across the world with antibodies to allow them to carry out research. They are from reference labs in other countries who have already done a lot of work and have got to the point where they have reached their limit of what they can do and then they send their samples to NHSBT," he said. The head of the lab Nicole Thornton told him: “Often if the labs cannot resolve it we have to do a lot more work to possibly discover a new blood group or a blood group system if its not easily resolvable in our hands. And that is where the interesting cases come from. We have some new work in the pipeline at the moment that we think that’s going to lead to some new antigens in current blood systems but also some new blood group systems in addition to the one we have just published."