Breakthrough as scientists discover previously unknown blood type after 50-year mystery

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

For more than half a century, a series of rare but devastating complications from simple blood transfusions have been linked to the elusive absence of a key immune system-triggering ‘antigen’ molecule known as the AnWj blood group antigen.

But now a team of researchers in the UK have identified a compound found in 99.9 percent of human blood that carries this AnWj antigen. They call 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 tasked with such medical mysteries by healthcare providers around the world.

‘If the labs can’t solve it, we often have to do a lot more work,’ says Nicole Thornton from the NHSBT red blood cell lab. ‘That’s where the interesting cases come from.’

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

“Because some antigens can trigger a patient’s immune system to attack the transfused blood, safe blood transfusions depend on careful blood typing and cross-matching,” the American Red Cross notes in their explanation of the problem.

While the new discovery is likely far too unknown to be widely used beyond the eight most common blood types (A+, A-, B+, B-, O+, O-, AB+ and AB-), researchers estimate that its identification could save hundreds of lives each year.

Thornton, head of NHSBT’s International Blood Group Reference Laboratory ‘Red Cell Reference’, her team and scientists from the University of Bristol worked with different blood samples and tools to ultimately identify where the AnWj antigens are located.

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

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

“We had to do multiple studies to gather the evidence we needed to establish this blood group system,” Dr. Satchwell told reporters in a press release.

The clincher turned out to be a method called whole exome sequencing, a more cost-effective and customized form of whole genome sequencing that focuses exclusively on a particular patient’s DNA that encodes or makes proteins.

This process helped the team capture the rare genetic cases where the DNA sequence Deletions in the MAL gene prevented the coding of the Mal protein.

“We wouldn’t have achieved this without exome sequencing,” said Louise Tilley, a senior researcher at NHSBT’s Red Cell Reference in a statement.

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

The MAL gene deleted in these rare cases gets its name from 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 and in the stability of cell membranes.

“AnWj-positive individuals were shown to express full-length Mal on their red cell membranes, which was not the case on the membranes of AnWj-negative individuals,” the team noted in their new study for the journal Blood.

“The genetic background of AnWj has been a mystery for over 50 years, and I have spent almost 20 years of my career trying to unravel it,” Tilley told reporters.

“It is a tremendous achievement,” she added, “and the culmination of a long team effort to finally establish this new blood grouping system and provide the best care for rare, but important, patients.”

As Tilley emphasized to the BBCit is “very difficult to put a number” on how many people will benefit from the newly identified Mal protein.

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

In their new study, Tilley and her colleagues reported that “the most common reason for being AnWj negative is having a hematologic disorder or certain cancers that suppress antigen expression.”

HEmatologic diseases, which affect millions of Americans, include rare genetic disorders, sickle cell disease, conditions related to HIV, 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 a family of Arab-Israelis.”

It is precisely these genetically AnWj-negative patients who will benefit most from Mal’s discovery, as new laboratory tests will be developed to match them with the right blood for any necessary blood transfusions.

“Uncovering the genetic basis for AnWj is one of our most challenging projects,” Thornton said.

‘Now genotyping tests can be designed to identify genetically AnWj-negative patients and donors. Such tests can be added to existing genotyping platforms.’

A contributor to Thornton’s ‘Red Cell Reference’, Philip Brown, explained that he himself had been diagnosed about 20 years ago with a form of leukemia that required life-saving medical care. blood transfusions and a bone marrow transplant.

“Anything we can do to make our blood safer and better suited to patients’ needs is a step in the right direction,” he said.