For over half a century, a peculiar medical anomaly puzzled hematologists: a blood sample from 1972 lacked a surface molecule present in all other known human red blood cells. Now, after decades of investigation, scientists in the UK and Israel have officially described this as a new human blood group system – the MAL system. The discovery, published in 2024, marks a significant achievement in blood science and promises improved care for patients with this rare blood type.
The Long Quest for Identification
The mystery began with a pregnant woman’s sample collected in 1972. The missing molecule, later identified as the AnWj antigen, prompted nearly two decades of personal research for hematologist Louise Tilley of the UK National Health Service. “It represents a huge achievement… to finally establish this new blood group system,” Tilley stated in September 2024.
The difficulty stemmed from the extreme rarity of the genetic cases. Over 99.9% of people carry the AnWj antigen, which resides on a myelin and lymphocyte protein. This led researchers to name the new system MAL, after the protein itself.
Why Blood Group Systems Matter
Humans have multiple blood group systems beyond the familiar ABO and Rh types. These systems are defined by a vast array of proteins and sugars coating red blood cells, acting as ‘self’ markers to distinguish from foreign substances. Incompatible transfusions can trigger severe reactions or even death, making accurate blood typing crucial. Most major groups were identified in the early 20th century, but many discovered since, like the Er system (described in 2022), are limited to small populations. The MAL system falls into this category.
The Genetic Basis of MAL Negativity
Individuals with two mutated copies of the MAL gene lack the AnWj antigen, resulting in an AnWj-negative blood type, like that of the original 1972 patient. Researchers also found three cases of AnWj negativity not linked to genetic mutation, suggesting certain blood disorders can suppress the antigen.
The MAL protein plays a vital role in cell membrane stability and cellular transport. Notably, the AnWj antigen is absent in newborns but appears shortly after birth, adding another layer to the mystery.
Implications for Patient Care
The identification of the genetic markers behind the MAL mutation allows for precise testing. Patients can now determine if their AnWj-negative status is inherited or a sign of an underlying medical condition. Rare blood quirks can be devastating, and a better understanding of them translates directly into saved lives.
“MAL is a very small protein with some interesting properties which made it difficult to identify… we needed to pursue multiple lines of investigation.” – Tim Satchwell, University of the West of England cell biologist.
The research, published in Blood, concludes that while the mutation itself isn’t linked to other abnormalities, accurate diagnosis is critical for safe blood transfusions and identifying potential health concerns.
