For half a century, a tiny quirk on the surface of red blood cells has puzzled doctors and put a small group of patients at risk during transfusions. That mystery has now been resolved with the identification of a new human blood group system, named MAL, which finally explains a stubborn pattern of dangerous reactions. The finding turns an obscure antigen called AnWj from a clinical headache into a mapped and testable part of human biology.
By tying the AnWj antigen to a specific gene and defining MAL as the 47th blood group system, researchers have closed a 50-year gap in transfusion medicine and opened a new chapter in precision matching. I see this as a rare example of a long-running bedside problem being solved by painstaking lab work, with immediate consequences for how hospitals classify and safeguard blood.
Cracking a 50-year puzzle in the blood bank
For decades, a handful of patients around the world baffled transfusion specialists because their blood reacted in ways that did not fit the familiar ABO or Rh patterns. The common thread was an obscure marker known as the AnWj antigen, first described in 1972 but never fully explained, which sometimes vanished from a patient’s red cells or triggered severe reactions when they received otherwise compatible blood. According to a research team, these unexplained cases kept resurfacing in hospital labs, hinting that a missing piece of the blood group puzzle was still out there.
The breakthrough came when specialists in transfusion medicine and molecular genetics joined forces to track the problem back to its source. A group led by NHS Blood and systematically collected rare samples from patients who lacked AnWj or had made antibodies against it, then sequenced their DNA to look for a shared defect. Over time, they homed in on a small membrane protein on red cells, showing that changes in its gene correlated with the presence or absence of the antigen and with the dangerous reactions that had worried clinicians for so long.
From AnWj to MAL, the 47th blood group system
Once the genetic link was clear, the team could do something that had eluded scientists for 50 years: define a new blood group system around AnWj. The protein involved is encoded by the MAL gene, and that name has now been adopted for the entire system, which becomes the 47th recognized category in human blood typing. In a detailed account, Researchers describe how MAL sits alongside ABO, Rh and other systems, with its own antigen and its own pattern of inheritance that can be tracked in families and across populations.
The clinical significance lies in the patients who lack this antigen entirely, known as AnWj negative, who can form potent antibodies if they are exposed to MAL positive blood. A focused Press summary notes that these individuals are at particular risk during transfusion, because standard screening does not routinely pick up MAL incompatibility. By formally naming the system and tying it to a gene, laboratories can now design tests that identify MAL status in donors and recipients, reducing the chance that these rare but serious reactions will be missed.
Why a “rare” blood group matters in real-world care
It might be tempting to treat MAL as a curiosity, relevant only to a tiny number of patients, but the history of AnWj shows why that would be a mistake. People who are AnWj negative are uncommon, yet when they need blood, the wrong unit can provoke a severe immune response that destroys transfused cells and destabilizes already fragile patients. A detailed clinical description explains that the inherited AnWj-negative phenotype can be completely silent until a transfusion or pregnancy exposes the immune system to MAL positive cells, at which point antibodies can form and complicate future care.
By identifying MAL, scientists have given blood services a new tool to protect these patients. New genotyping approaches can now flag donors who are AnWj negative, creating a small but vital pool of compatible units for those who need them. Reporting on the New MAL system highlights that it becomes the 47th recognized group and that targeted testing can be integrated into existing workflows for complex cases, such as people with multiple antibodies or those requiring repeated transfusions for conditions like sickle cell disease or thalassemia.
The genetics behind MAL and the 50-year search
At the heart of the discovery is a simple but powerful idea: every blood group antigen must be encoded somewhere in the genome, and if clinicians can see the antigen, geneticists should be able to find its gene. For AnWj, that search took 50 years because the antigen is present on most people’s red cells and only disappears in rare inherited cases or in certain diseases. A technical analysis notes that, According to recent study, the AnWj antigen is located on the MAL gene, according to the researchers, confirming that specific mutations in this gene remove the antigen from the cell surface.
That genetic mapping does more than satisfy scientific curiosity, it explains why some patients temporarily lose AnWj during severe illness and then regain it after recovery. A detailed overview of the New human blood group discovered describes how a rare genetic mutation can permanently remove the antigen, while other conditions can suppress its expression without altering the underlying DNA. A companion discussion of the Importance of AnWj blood discovery explains that some patients get AnWj back after recovery, which helps clinicians distinguish between inherited MAL negativity and transient loss due to disease.
Inside the lab: rare samples, new tests and a global effort
Solving a 50-year-old problem required more than clever sequencing, it depended on a global network of clinicians who recognized unusual reactions and saved samples for future study. A detailed report on the work notes that Scientists involved in the project had to track down rare donors and patients whose blood carried the crucial clues. Another account highlights that NHS Blood and Transplant experts had been working on the project for 20 years, gradually building the evidence needed to convince international blood group committees to recognize MAL as a distinct system.
In the lab, the challenge was to show that the MAL protein really carries the AnWj antigen and that altering it changes a person’s blood group status. A technical explanation of Unraveling the AnWj blood group describes how researchers used cell lines and gene editing to prove that removing MAL strips AnWj from the surface, while restoring the gene brings it back. Another summary of New MAL blood group discovered emphasizes that this work has immediate implications for blood transfusions and donor matching, since genetic tests can now be built to detect MAL status even when serological reagents are scarce.
More from Morning Overview