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."
