Findings could lead to new clinical laboratory tests to screen for individuals with increased risk of blood transfusion complications
Pathologists and clinical laboratory scientists who understand the complexities of blood typing from one human to another will be interested to learn that a 50 year-old mystery has brought about an exciting new discovery—a new human blood group.
British and Israeli scientists led by the UK’s NHS Blood and Transplant (NHSBT) and the University of Bristol discovered the meaning behind a missing protein molecule found in a pregnant woman five decades ago. This anomaly has now been given its own blood group identification called MAL, according to a University of Bristol new release.
“Some people can lack this blood group due to the effect of illness, but the rare inherited form of the AnWj-negative phenotype has only been found in a handful of individuals—though due to this discovery it will now be easier to find others in the future,” the news release notes.
This is important because receiving mismatched blood can be fatal.
“AnWj is a high-prevalence red blood cell (RBC) antigen in the ISBT 901 series. Only nine reports of anti-AnWj have been published since it was first documented in 1972,” according to a 2012 article published by the American Association of Blood Banks, now known as the Association for the Advancement of Blood and Biotherapies (AABB).
For even the small proportion of the population with this new blood group, diagnosing its presence can have a major impact while preventing unwanted harm.
“The work was difficult because the genetic cases are very rare. We would not have achieved this without exome sequencing, as the gene we identified wasn’t an obvious candidate and little is known about Mal protein in red cells,” said Louise Tilley, PhD, Senior Research Scientist, IBGRL Red Cell Reference at NHS Blood and Transplant, in the news release.
The researchers published their findings in Blood, a journal of the American Society of Hematology, titled, “Deletions in the MAL Gene Result in Loss of Mal Protein, Defining the Rare Inherited AnWj-Negative Blood Group Phenotype.”
“The genetic background of AnWj has been a mystery for more than 50 years, and one which I personally have been trying to resolve for almost 20 years of my career,” said Louise Tilley, PhD (above), Senior Research Scientist, IBGRL Red Cell Reference at NHS Blood and Transplant, in the news release. “It represents a huge achievement, and the culmination of a long term effort, to finally establish this new blood group system and be able to offer the best care to rare, but important, patients,” she added. Clinical laboratory scientists involved in blood banking will want to keep updated as further research into this new blood group is published. (Photo copyright: NHS Blood and Transplant.)
Unraveling the Mystery
In 1972, scientists were stumped by a pregnant woman with a blood sample that was “mysteriously missing a surface molecule found on all other known red blood cells at the time,” Science Alert reported. The AnWj antigen that was missing in that patient’s blood is present in 99.9% of human blood samples.
“Researchers found that the AnWj antigen is carried on the Mal protein. While illness can cause some people to lose the AnWj antigen, inherited cases of the AnWj-negative phenotype are extremely rare. Using whole exome sequencing on five genetically AnWj-negative individuals, researchers confirmed that, in these cases, the participants lacked the antigen due to homozygous deletions in the MAL gene,” an AABB news release stated.
The researchers named the group with the missing antigen the MAL blood group (short for Myelin and Lymphocyte Protein) which is where the antigen resides.
Genetic sequencing enabled the scientists to locate the gene when they “inserted the normal MAL gene into blood cells that were AnWj-negative. This effectively delivered the AnWj antigen to those cells,” Science Alert noted.
Mutated MAL genes result in the AnWj-negative blood type. The team discovered three patients with the blood type and no mutation, “Suggesting that sometimes blood disorders can also cause the antigen to be suppressed,” Science Alert added. The researchers also discovered that AnWj isn’t present in newborns but arrives sometime after they are born.
“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,” Science Alert said.
The discovery that “the Mal protein is responsible for binding AnWj antibodies” could lead to new clinical laboratory tests to screen for patients at risk from blood transfusions, AABB noted in its news release.
Facing the Challenge
Scientists had to overcome many challenges to uncover the details of this blood type. The complexity of the protein further hindered their efforts.
“MAL is a very small protein with some interesting properties which made it difficult to identify, and this meant we needed to pursue multiple lines of investigation to accumulate the proof we needed to establish this blood group system,” said Tim Satchwell, PhD, senior lecturer and cell biologist at the University of the West of England, in the University of Bristol news release.
“Resolving the genetic basis for AnWj has been one of our most challenging projects,” Nicole Thornton, head of IBGRL Red Cell Reference at NHSBT told the AABB. “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.”
It’s hard to pinpoint how many individuals will benefit by testing for the blood group, Tilley told the BBC. Nevertheless, “the NHSBT is the last resort for about 400 patients across the world each year,” the BBC reported.
While more research needs to be done, the initial discovery is promising and may lead to new clinical laboratory tests to identify individuals who could be severely harmed should they receive the wrong blood type during a transfusion.
—Kristin Althea O’Connor
Related Information:
British Researchers Discover New Blood Group
NHS Blood and Transplant-Led Team Discovers New Blood Group System MAL
Researchers Discover New Blood Group System—MAL
New Blood Group Solves Half a Century of Mystery
Scientists Crack a 50-Year Mystery to Discover a New Set of Blood Groups
The Discovery of the MAL Blood Group: A Breakthrough in Understanding Rare Blood Types
Anti-AnWj Causing Acute Hemolytic Transfusion Reactions in a Patient with Aplastic Anemia
