Scientific breakthrough: previously unknown blood type discovered after 50 years of mystery

A breakthrough discovery of a new blood protein will finally help doctors identify patients whose immune systems react violently to nearly all blood transfusions.

For more than half a century, a set of rare but devastating complications resulting from simple blood transfusions have been linked to the elusive absence of a key “antigen” molecule that triggers the immune system, known as the AnWj blood group antigen.

But now a team of researchers in the UK has identified which compound, present in 99.9 percent of human blood, contains this AnWj antigen. They have named it the “Mal” protein.

This 50-year-old cold case was solved by blood detectives from the UK’s National Health Service Blood and Transplant (NHSBT) group, who are routinely assigned to solve such medical mysteries by healthcare providers around the world.

“Often if the labs can’t solve the problem, we have to do a lot more work,” said Nicole Thornton from NHSBT’s red blood cell laboratory. “That’s where the interesting cases come from.”

The four main blood types and their positive or negative variations are defined by the presence or absence of two key antigens, A and B, along with another protein called the Rh factor, the presence of which equates to so-called positive blood types.

“Since some antigens can cause a patient’s immune system to attack the transfused blood, safe blood transfusions depend on careful blood typing and cross-matching,” the statement said. American Red Cross notes in his explanation of the topic.

While the new discovery will likely be too obscure to merit widespread use alongside the eight most common blood types (A+, A-, B+, B-, O+, O-, AB+ and AB-), its identification could help save hundreds of lives each year, the researchers estimated.

Thornton, director of NHSBT’s Red Cell Reference Laboratory, her team and scientists from the University of Bristol worked with a variety of blood samples and tools to ultimately identify where the AnWj antigens reside.

Their work even included a 2015 sample provided by the anonymous woman who was the first person found to be “AnWj negative” in the 1970s.

“Mal is a very small protein with some interesting properties that made it difficult to identify,” he said. Dr. Tim Satchwellwho assisted in the research while a researcher at the University of Bristol.

“We needed to pursue multiple lines of research to accumulate the evidence we needed to establish this blood group system,” Dr. Satchwell told reporters in a news release.

The clincher turned out to be a method called “whole exome sequencing,” a more cost-effective and personalized form of whole-genome sequencing that focuses only on a given patient’s DNA that codes for or creates proteins.

This process helped the team focus on the rare genetic cases where the DNA sequence… Deletions in the MAL gene prevented the encoding of the Mal protein.

“We couldn’t have done it without exome sequencing,” said Louise Tilley, senior research scientist at NHSBT’s Red Blood Cell Reference Centre. In a statement.

“The gene we identified was not an obvious candidate and little is known about the Mal protein in red blood cells,” he said.

The MAL gene that was deleted in these rare cases is named after the “Myelin and Lymphocyte” (Mal) protein it encodes.

Mal proteins—’multi-pass membrane proteolipids’ coated with fatty lipid molecules—appear to play an essential role in the movement of cells through the bloodstream as well as in the stability of cell membranes.

‘AnWj-positive individuals have been shown to express full-length Mal in their red blood cell membranes, which was not present in the membranes of AnWj-negative individuals,’ the team noted in their new study for the journal Blood.

“The genetic origin of AnWj has been a mystery for over 50 years, and it’s one I’ve personally been trying to solve for nearly 20 years of my career,” Tilley told reporters.

“This is a tremendous achievement,” he added, “and the culmination of a long team effort to finally establish this new blood group system and be able to offer the best care to rare but important patients.”

As Tilley emphasized, BBCIt is quite difficult to estimate how many people will benefit from the newly identified Mal protein.

But he noted that NHSBT is usually the last hope for around 400 patients around the world each year.

In their new study, Tilley and colleagues reported that “the most common reason for being AnWj-negative is due to having a hematologic disorder or some types of cancer that suppress antigen expression.”

IHematologic diseases, which affect millions of Americans, include rare genetic disorders, sickle cell disease, HIV-related conditions and complications from treatments such as chemotherapy or blood transfusions.

“Only a very small number of people are AnWj negative due to a genetic cause,” the team noted. Among them: “five genetically AnWj negative individuals in the study, including one family of Israeli Arabs.”

These genetically AnWj-negative patients will benefit most from Mal’s discovery, as new laboratory tests will be devised to help match them with the correct blood for any necessary transfusions.

“Solving the genetic basis of AnWj has been one of our most challenging projects,” Thornton said.

“Genotyping tests can now be designed to identify patients and donors who are genetically negative for AnWj. These tests can be added to existing genotyping platforms.”

A member of staff at Thornton’s Red Cell Reference, Philip Brown, explained that he himself had been diagnosed with a form of leukaemia about 20 years ago which required life-saving surgery. blood transfusions and a bone marrow transplant.

“Anything we can do to make our blood much safer and more compatible with patients is a definite step in the right direction,” he said.