Scientists finally solve a 30-year-old mystery by discovering a new set of blood groups

Turns out, uncovering the exceedingly rare Er system could be lifesaving.
Sade Agard
Hands holding a blood bag in a hospital setting
Transfusion blood bag


According to recent research published in the journal Blood, scientists have discovered a new set of blood groups called the Er blood group. The discovery provides insight into a 30-year-old mystery in which two women tragically lost their babies. It will advance knowledge of the care needed to treat people with a variation of the rare blood group.

In a new study, scientists from NHS Blood and Transplant (NHSBT) and the University of Bristol studied one mother's blood sample against several others to unpick precisely what made her blood different.

They looked at three blood group antigens (molecules on the surface of red blood cells that can cause an immune system attack) that did not fit into any established blood group system. In the process, they confirmed a new set of blood grouping—the Er system—the 44th to be described. It is tied to a particular protein found on the surface of red blood cells called Piezo1.

'Discovering a new blood group system is like discovering a new planet'

“Discovering a new blood group system is like discovering a new planet. It enlarges the landscape of our reality,” highlights Saint Louis University School of Medicine's Daniela Hermelin to WIRED, who was not involved in the study.

The new study demonstrates the genetic origins of three of these antigens (Era, Erb, and Er3), as well as the finding of two new antigens (Er4 and Er5).

The recently identified blood group variations, Er4 and Er5, are exceedingly rare and have been connected to hemolytic illness in fetuses and newborns. This illness develops when the mother's immune system attacks her unborn child's blood.

According to an article by WIRED, Nicole Thornton, one of the study's authors, had a sense that Piezo1 was involved after she compared the genomes of patients in the study.

Genetic variations that code for Piezo1, a protein linked to the new blood system, perceive blood cells as 'foreign'

She and her colleagues discovered that individuals with various Er blood types have different gene variations that code for this protein. A small percentage of people have different amino acids or protein building blocks in their Piezo1 protein as a result of those genetic variations. Their bodies' immune systems perceive blood cells with the more frequent Piezo1 protein as foreign.

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She further explains that the findings increase our understanding of the potential effects of blood incompatibility on expectant mothers and their unborn children. Now that cases of blood incompatibility may be linked to the Er blood group, it improves the likelihood that clinicians will be able to accurately identify and treat such a condition by providing the infant with a blood transfusion while still in the womb.

British team beats U.S. researchers in discovering the mysteries of the new Er blood group

Another team of researchers from the other side of the Atlantic had been striving to unravel the mysteries of the new Er blood group, according to WIRED. The British team just so happened to beat them to it.

Still, a participant from 'the other study,' Connie Westhoff of the New York Blood Center, claims the research may not be over. Westhoff speculates that further genetic mutations may be connected to this rare blood discovery.

What are blood group systems?

The two primary blood group systems, the ABO and Rh- systems, are known to the majority of individuals. There are other additional blood group systems, each with a unique range of reaction risk. Additionally, different blood group antigens exist within each blood group system.

While the majority of blood group systems (aside from ABO) may go unnoticed by the general public, this does not mean that they are irrelevant. Minor variations can have clinical consequences for transfusion-dependent patients as well as pregnant women.


Despite the identification of the high incidence red cell antigen Era nearly 40 years ago, the molecular background of this antigen, together with the other two members of the Er blood group collection, has yet to be elucidated. Whole exome and Sanger sequencing of individuals with serologically defined Er alloantibodies identified several missense mutations within the PIEZO1 gene, encoding amino acid substitutions within the extracellular domain of the Piezo1 mechanosensor ion channel. Confirmation of Piezo1 as the carrier molecule for the Er blood group antigens was demonstrated using immunoprecipitation, CRISPR/Cas9-mediated gene knockout and expression studies in an erythroblast cell line. We report the molecular bases of five Er blood group antigens: the recognised Era, Erb and Er3 antigens; and two novel high incidence Er antigens, described here as Er4 and Er5, establishing a new blood group system. Anti-Er4 and anti-Er5 are implicated in severe hemolytic disease of the fetus and newborn (HDFN). Demonstration of Piezo1, present at just a few hundred copies on the surface of the red blood cell, as the site of a new blood group system highlights the potential antigenicity of even low abundance membrane proteins and contributes to our understanding of the in vivo characteristics of this important and widely studied protein in transfusion biology and beyond.