When a pregnant woman had her blood sampled back in 1972, doctors discovered it was mysteriously missing a surface molecule found on all other known red blood cells at the time.
After 50 years, this strange molecular absence finally led researchers from the UK and Israel to describe a new blood group system in humans.
“It represents a huge achievement, 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,” UK National Health Service hematologist Louise Tilley says, after nearly 20 years of personally researching this bloody quirk.
While we’re all more familiar with the ABO blood group system and the rhesus factor (that’s the plus or minus part), humans actually have many different blood group systems based on the wide variety of cell-surface proteins and sugars that coat our blood cells.
Our bodies use these antigen molecules, amongst their other purposes, as identification markers to separate ‘self’ from potentially harmful not-selves.
If these markers do not match up when receiving a blood transfusion, this life-saving tactic can cause reactions or even end up being fatal.
Most major blood groups were identified early in the 20th century. Many discovered since, like the Er blood system first described by researchers in 2022, only impact a small number of people. This is also the case for the new blood group.
“The work was difficult because the genetic cases are very rare,” explains Tilley.
Previous research found more than 99.9 percent of people have the AnWj antigen that was missing from the 1972 patient’s blood. This antigen lives on a myelin and lymphocyte protein, leading the researchers to call the newly described system the MAL blood group.
When someone has a mutated version of both copies of their MAL genes, they end up with an AnWj-negative blood type, like the pregnant patient. Tilley and team identified three patients with the rare blood type that didn’t have this mutation, suggesting that sometimes blood disorders can also cause the antigen to be suppressed.
“MAL is a very small protein with some interesting properties which made it difficult to identify and meant we needed to pursue multiple lines of investigation to accumulate the proof we needed to establish this blood group system,” explains University of the West of England cell biologist Tim Satchwell.
To determine they had the correct gene, after decades of research, the team inserted the normal MAL gene into blood cells that were AnWj-negative. This effectively delivered the AnWj antigen to those cells.
The MAL protein is known to play a vital role in keeping cell membranes stable and aiding in cell transport. What’s more, previous research found that the AnWj isn’t actually present in newborn babies but appears soon after birth.
Interestingly, all the AnWj-negative patients included in the study shared the same mutation. However, no other cell abnormalities or diseases were found to be associated with this mutation.
Now that the researchers have identified the genetic markers behind the MAL mutation, patients can be tested to see if their negative MAL blood type is inherited or due to suppression, which could be a sign of another underlying medical problem.
These rare blood quirks can have devastating impacts on patients, so the more of them we can understand, the more lives can be saved.
This research was published in Blood.
