In a twist worthy of a medical detective novel, a strange lab result from a pregnant woman more than five decades ago has led researchers to define an entirely new blood group system, with serious implications for rare patients needing safe blood or during pregnancy.
A missing marker that baffled scientists for decades
In 1972, a routine blood test from a pregnant woman in the UK produced a result that simply did not fit the rules of the time. Her red blood cells were missing a molecule that every other tested person seemed to have. The molecule, called AnWj, sat on the surface of red blood cells and was treated as almost universal.
For years, this case sat in the background of transfusion medicine, known to specialists but with no clear explanation. Most people, well over 99.9 percent of the population, carry AnWj without issue. Yet this woman, and a scattering of patients since, did not. That small group would eventually push scientists to rethink the catalogue of human blood types.
The trail from a single pregnant patient in 1972 to a defined blood group in 2024 shows how stubborn medical mysteries can reshape clinical practice.
By 2024, after painstaking work by teams in the UK and Israel, researchers were able to show that the “missing” molecule was part of a previously unrecognised blood group system. They named it MAL, after the protein on which AnWj sits: the myelin and lymphocyte protein.
How the MAL blood group fits into the bigger picture
Most people think of blood types in two simple labels: A, B, AB or O, plus the positive or negative Rh factor. Those are just the most clinically visible pieces of a much more complex picture. In reality, human blood cells carry dozens of systems of sugars and proteins, each forming its own blood group category.
These surface molecules are called antigens. They act as ID tags. The immune system uses them to recognise which cells belong in the body and which do not. If transfused blood carries antigens a patient’s immune system regards as foreign, the body can attack those cells.
A mismatched blood transfusion is not just “less effective” — it can trigger dangerous reactions, including kidney damage, shock, and in severe cases, death.
Most of the major blood group systems were identified in the early 20th century. More recent ones, such as the Er system reported in 2022, tend to be rare and hidden within unusual cases. The MAL system falls firmly into that category: it is vanishingly rare, but potentially critical when it matters.
What makes the MAL blood group different
The MAL blood group is defined by the presence or absence of the AnWj antigen on red blood cells.
- People with normal MAL genes: AnWj-positive (the overwhelming majority).
- People with two mutated MAL gene copies: AnWj-negative, forming the rare MAL blood group phenotype.
Researchers showed that when both copies of a person’s MAL gene are altered, their red blood cells lack AnWj. That matches the pattern seen in the original 1972 patient. In the new study, all genetically AnWj-negative participants shared the same mutation in MAL, yet they did not show other obvious diseases or red cell defects.
That point matters for patients and clinicians: having this rare blood type on its own does not automatically mean poor health. The risk comes during transfusion or pregnancy, when antibody reactions can occur.
How scientists finally pinned down the MAL gene
Unravelling the MAL system was not quick science. The genetic pattern is exceptionally rare, so researchers had very few real-world cases to work from. According to the team, multiple strands of evidence had to be woven together before they could confidently classify a new blood group.
One of the key experiments involved taking blood cells that lacked AnWj and inserting a standard, functional MAL gene into them. Once the healthy gene was added, the AnWj antigen appeared on the surface of those cells.
By restoring a normal MAL gene in AnWj-negative cells and watching the missing antigen reappear, scientists effectively proved that MAL is the molecular “address” for this blood group.
This kind of gene “rescue” experiment is a powerful way to show cause and effect. It strengthened the argument that MAL is the controlling factor and that the AnWj antigen is part of a coherent blood group system rather than a random quirk.
Suppressed, inherited, or something else?
Not all AnWj-negative patients fit the same genetic mould. While many carried the MAL mutation, researchers also identified several people whose red cells lacked the antigen but whose MAL gene was not altered.
That pattern suggests a second mechanism. In some blood disorders, the antigen might be switched off or suppressed rather than removed by mutation. Those cases are exciting for clinicians because they may act as a warning sign that something else is going wrong in the blood or bone marrow.
Now that the MAL gene has been mapped and the specific mutation linked to this phenotype, laboratories can distinguish between inherited MAL blood type and suppression caused by disease. That difference can directly affect how patients are monitored and treated.
Why newborns are a special case
Previous work showed that AnWj is not present on the red cells of newborn babies. It appears only shortly after birth. That timing is unusual, as many red blood cell antigens are already visible in late pregnancy.
This delayed appearance could influence how doctors interpret tests in neonates and how they think about maternal antibodies during and after pregnancy. If a mother has antibodies against AnWj and the baby is AnWj-negative, the dynamics across the placenta may be different from classic Rh or ABO incompatibility scenarios.
What this means for transfusion and pregnancy care
The new MAL blood group is rare, but for the people who have it, details matter. In a transfusion setting, an AnWj-negative patient could react to blood that carries AnWj if they have developed antibodies against it. For pregnant patients, antibodies targeting fetal red cells can sometimes trigger haemolytic disease of the fetus and newborn, a condition where the baby’s red cells are destroyed.
Hospitals and blood banks now have a clearer route to testing for MAL-related markers. Once a case is flagged, specialist centres can look for compatible donors or arrange tailored care. This mirrors how other rare blood groups are handled: they may only affect a small fraction of the population, but the stakes for those individuals are high.
| Aspect | Common blood groups (ABO/Rh) | Rare systems like MAL |
|---|---|---|
| Frequency | Present in everyone, with familiar patterns | Detected in a tiny fraction of people |
| Main concern | Routine transfusions and pregnancy matching | High-risk, complex cases and specialist care |
| Testing | Standard in all hospitals | Usually done in reference labs |
| Public awareness | Well known to patients | Mostly known to transfusion specialists |
Key terms that help make sense of blood group research
Two terms come up repeatedly in this story: antigens and antibodies. Understanding those helps clarify why such a tiny protein like MAL matters.
- Antigen: A molecule on a cell’s surface that can be recognised by the immune system.
- Antibody: A Y‑shaped protein made by the immune system that binds to a specific antigen.
When you receive blood that carries an antigen you lack, your immune system might already have antibodies against it, or may build them afterwards. Once those antibodies are present, future transfusions or pregnancies involving that antigen can be risky. Rare blood groups, such as MAL, add another layer to this matching game.
How this kind of work affects everyday patients
Most people will never hear the phrase “MAL blood group” during a hospital stay. Your local emergency department is far more focused on getting your ABO and Rh status right, and for good reason: those mismatches are common and potentially dramatic.
Yet, behind the scenes, reference labs and national blood services maintain databases of rare donors and track unusual antibodies. When a patient has repeated transfusions, such as someone with sickle cell disease or certain cancers, the risk of developing complex antibodies rises. In those situations, having well-characterised systems like MAL ready in the textbooks can stop a serious reaction before it starts.
The new MAL system also highlights how genetics and transfusion medicine are steadily merging. Testing for mutations that define blood groups is increasingly routine in advanced settings. Over time, more patients may have their extended blood group profile stored on record, cutting delays when urgent transfusion is needed.
For individuals who are found to be AnWj-negative, there are practical questions: they may be advised to carry documentation, and blood services might encourage them to donate, since matching rare patients often relies on a very small pool of compatible donors.
