Researchers Identify New Blood Group After 50 Year Mystery

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 to researchers from the UK and Israel describing a new blood group system in humans. The team published their paper about the discovery in 2024. "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 said last September, after nearly 20 years of personally researching this bloody quirk.

Despite the fact that we are all more familiar with the ABO blood group system and the Rh factor (the plus or minus part), humans actually have a number of distinct blood group systems that are based on the numerous 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 true for the new blood group.

Previous research revealed that more than 99.9% of people possess the AnWj antigen, which was absent from the blood of the 1972 patient. 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 his group found three people who had the rare blood type but did not have this mutation. This suggests that other blood disorders can also suppress the antigen. "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," explained University of the West of England cell biologist Tim Satch well.

After decades of research, the team inserted the normal MAL gene into AnWj-negative blood cells to confirm that they had the correct gene. The AnWj antigen was effectively delivered to those cells by this. 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.

Patients can now be tested to determine whether their negative MAL blood type is inherited or due to suppression—which could be a sign of another underlying medical issue—now that the researchers have identified the genetic markers that are responsible for the MAL mutation. These rare blood quirks can have devastating impacts on patients, so the more of them we can understand, the more lives can be saved.