Researchers from NHS Blood & Transplant (NHSBT) and the University of Bristol have uncovered a unique new blood group system. Blood reported the findings, which also provide the answer to a 30-year riddle.
The presence or lack of certain proteins on the surface of red blood cells, referred to as blood groups, determines a person’s blood type. There are several additional significant blood types, even though the majority of people are familiar with concepts like ABO or Rh (the plus or minus). The likelihood of alloimmunization (the process by which a person creates an antibody against a blood group antigen that they do not contain) emerges when there is a mismatch between one person’s blood and that of another. By inciting an immune system assault, the presence of alloantibodies might have clinical effects during transfusion or pregnancy.
The International Blood Group Reference Laboratory (IBGRL) of NHSBT and the School of Biochemistry at the University of Bristol led an international collaboration to look into a 30-year mystery involving the origin of three known but genetically uncharacterized antigens that did not correspond to any known blood group system.
In this study, people who had alloantibodies against a group of antigens known as Er that were discovered more than 30 years ago were examined using a potent method that allowed simultaneous investigation of all their gene coding DNA sequences. These individuals would produce an altered protein on their cell surfaces as a consequence of specific alterations found in the gene encoding the Piezo1 protein. To conclusively demonstrate that alloantibodies to Er antigens, including two that have never been reported, bind to Piezo1 and that Piezo1 is necessary for Er antigen production, the Piezo1 protein was first deleted and then reintroduced in an immortalized cell-line created in Bristol.
The scientists established Er as a new blood group system by clearly demonstrating that Piezo1, a protein of broad biological importance, is the carrier for these sites (and more) using a combination of cutting-edge DNA sequencing and gene-editing methods.
Sadly, the two pregnant women who had alloantibodies to two newly identified Er antigens revealed in this paper also tragically lost their kids. With the goal of providing the best treatment for patients with even the most uncommon blood types, scientists may now create new tests to detect people with uncommon blood groups thanks to their discovery of the genetic foundation for blood kinds. Despite the fact that there is still much to learn about Piezo1, the team’s discovery advances our understanding and marks yet another significant development in the field of blood sciences.
One of the research’s primary authors, Dr. Tim Satchwell of the University of Bristol, said, “This study is an excellent illustration of how new technologies may work in conjunction with more conventional methods to answer old concerns that were intractable not that many years ago. Even more fascinating is the discovery that Er is Piezo1, a protein that has attracted a lot of attention.”
Professor Ash Toye, Director of the NIHR Blood and Transplant Research Unit and Professor of Cell Biology at the University of Bristol, stated, “This discovery shows that the humble red blood cell may still astound us despite all of the research that has been done thus far. The red cell uses piezo proteins, which are mechanosensory proteins, to detect compression. Only a few hundred copies of the protein are found in each cell’s membrane. This work definitely emphasizes the significance of low expression proteins for transfusion therapy as well as their potential antigenicity.”