The agonizing loss of two newborns has provided scientists with key information about a group of rare blood types first discovered in humans 40 years ago.
By revealing the molecular identity with respect to a new blood type known as the Er system, the scientists hope their new study will help identify and treat some rare blood type incompatibilities, such as those between pregnant women and their fetuses.
“This work shows that even after all the research done to date, simple red blood cells can still surprise us,” says Ash Toy, a cell biologist at the University of Bristol.
The blood group is determined by the presence or absence of certain antigens, with the main types that people are familiar with being A, B, O, and AB (positive and negative), making up the eight blood types.
The classification of blood describes the presence and absence of groups of proteins and sugars that cover the surface of red blood cells. While they can serve a variety of purposes, our bodies typically use cell surface antigens as identification marks with which to separate ourselves from potentially dangerous invaders.
Different types of antibodies can be used to know the blood type, of which people know the ABO blood group system (indicating the presence or absence of one or both A and B antigens on the surface of red blood cells) and the Rhesus blood group system (one of the thirty-five known blood systems, and it is the second most important blood group system after the ABO blood group system). These systems are primarily important in blood transfusion.
But in fact, there are many different blood group systems that depend on a wide range of cell surface antigens and their variants.
The team studied the antigens of three blood types (molecules on the surface of red blood cells that can trigger an attack in the immune system) that do not fit into any of the existing blood group systems. In the process, they confirmed a new blood type called the Er system, which became the 44th blood type.
Most of the major blood groups were recognized in the early 20th century, but the last member of these groups, named Er, did not appear until 1982.
Six years later, the band’s version was called Erb. The scientists then identified the Er3 and Era antigens, and also discovered two new antigens (Er4 and Er5).
This system binds to a specific protein found on the surface of red blood cells called Piezo1.
The recently identified differences between Er4 and Er5 blood types are extremely rare and are associated with hemolytic disease in fetuses and newborns. This disease develops when a mother’s immune system attacks the blood of her unborn child.
Although it has been clear for decades that these blood cell antigens are present, very little has been known about their clinical effects.
When a blood cell appears with an antigen that our body does not classify as its own, the immune system is activated, sending out antibodies to report on the suspected antigen-containing cells in order to destroy them.
In some cases, maternal and fetal blood type incompatibility can cause problems if the mother’s immune system becomes sensitive to foreign antigens.
Antibodies produced in response can cross the placenta, causing hemolytic disease in the fetus (a blood disease that affects the fetus or newborn, which can be fatal).
Fortunately, there are several ways to prevent or even treat hemolytic disease in newborns these days, including injections for expectant mothers and blood transfusions for babies.
But there is, for one of the cases mentioned in the study, the failure of a blood transfusion after a caesarean section to save a baby’s life, indicating that doctors and researchers were unable to detect.
“The hint of these rare antibodies has been around for many years, but their rarity has made our understanding of them elusive until now,” Nicole Thornton, a serologist with the UK’s National Blood and Transplant Service (NHSBT), told Wired.
So, under the guidance of NHSBT serologist Vanya Kramatek Crowe Thornton and her colleagues analyzed the blood of 13 patients with suspected antigens. They identified five variants of Er antigens: known Era variants, Erb and Er3, and two new variants, Er4 and Er5.
By sequencing the patients’ genetic codes, Crowe and her team were able to identify the gene that codes for cell surface proteins. Surprisingly, it was a gene already known to medical science: PIEZO1.
“PIEZO1 proteins are mechanosensory proteins that red blood cells use to sense when they contract,” explains Ash Toy.
PIEZO1 is already associated with many well-known diseases: mice without the gene die before birth, and mice with the deleted gene in their red blood cells end up with fragile blood cells and overhydration.
The crew and team confirmed their findings by removing PIEZO1 in the erythrocyte lineage, a precursor of erythrocytes, and testing for antigens.
Undoubtedly, PIEZO1 is required for attachment of the Er antigen to the cell surface.
Since they found a high prevalence of the Er5 variant in the African population, the scientists suspect that this variant may have some benefit against malaria, like some of the other rare blood types found there.
Source: Science Alert.