A specimen of blood acquired from a pregnant individual in 1972 was found to be devoid of a specific surface molecule that was universally present on all other identified erythrocytes at that temporal juncture.
Over half a century onward, this peculiar anomaly has ultimately facilitated a cohort of researchers from the United Kingdom and Israel in characterizing a novel human blood group classification. The findings of this collaborative endeavor were disseminated in a peer-reviewed publication in the year 2024.
“This represents a monumental accomplishment, embodying the culmination of extensive collaborative efforts, to finally formalize this new blood group system and consequently provide optimal care for individuals with rare, yet significant, medical conditions,” stated hematologist Louise Tilley of the UK National Health Service in September 2024, following nearly two decades of dedicated investigation into this peculiar hematological phenomenon.
While the ABO blood group system and the Rh factor (commonly denoted as positive or negative) are widely recognized, humanity actually possesses an extensive array of distinct blood group systems. These variations are predicated upon the broad spectrum of proteins and saccharides that adorn the surface of our blood cells.
These particular antigen molecules serve, among their multifaceted roles, as identification markers, enabling our biological systems to differentiate between ‘self’ and potentially adversarial ‘non-self’ entities.
Should these surface markers exhibit incompatibility during a blood transfusion procedure, a treatment intended to preserve life can paradoxically precipitate adverse reactions or, in extreme cases, prove to be lethal.
The majority of principal blood groups were elucidated during the incipient stages of the twentieth century.
Numerous blood groups identified subsequently, such as the Er system first detailed in 2022, are exclusive to a limited segment of the population. This scenario mirrors the genetic basis of the recently documented blood group.
“The investigative process was fraught with challenges due to the extreme rarity of the genetic manifestations,” articulated Tilley.
Prior investigations revealed that an overwhelming majority, exceeding 99.9 percent, of individuals possess the AnWj antigen, which was conspicuously absent in the blood sample from the 1972 patient. Given that this antigen is associated with a myelin and lymphocyte protein, the research team designated the newly identified system as the MAL blood group.
When an individual inherits two aberrant copies of the MAL gene, they consequently exhibit an AnWj-negative blood phenotype, akin to the patient from 1972.
Tilley and her associates also identified three additional individuals with AnWj-negative blood types who did not present with this specific genetic mutation, suggesting that certain hematological disorders may impede the expression of this antigen.
“The MAL protein is a diminutive entity possessing intriguing characteristics that complicated its identification, necessitating the pursuit of multiple investigative avenues to amass the requisite evidence for establishing this blood group system,” elaborated University of the West of England cell biologist Tim Satchwell.
To definitively ascertain the implicated gene, after extensive research spanning several decades, the investigative team introduced the standard MAL gene into blood cells that were AnWj-negative. This intervention successfully conferred the AnWj antigen upon these cells.
The MAL protein is recognized for its critical function in maintaining the integrity of cell membranes and facilitating cellular transport mechanisms. Previous studies have indicated that the AnWj antigen is not present at birth but emerges shortly thereafter.
Every AnWj-negative participant in the study shared an identical genetic aberration. Nevertheless, no other cellular anomalies or pathological conditions were found to be associated with this specific mutation.
With the genetic determinants underlying the MAL mutation now elucidated, individuals can undergo assessment to ascertain whether their AnWj-negative blood type is an inherited trait or a consequence of antigen suppression – the latter potentially indicating an underlying medical issue.
These uncommon hematological variations can impose profound and adverse consequences on affected patients; therefore, a deeper understanding of these phenomena is paramount for salvaging lives.
This scientific investigation was formally presented in the journal Blood.
