Scientists cracked a 50-year blood group mystery that could protect rare transfusion patients

For more than 50 years, a red cell marker called AnWj sat in blood banks’ records with no known gene behind it. Louise Tilley of NHS Blood and Transplant (NHSBT) spent close to 20 of those years trying to find one. Her team in Bristol has now tied AnWj to the MAL gene, and with it created the 47th recognised blood group system.

The finding changes what a laboratory can do for a very small group of patients. People who lack AnWj can form antibodies against it, and a transfusion of ordinary blood then risks a serious reaction. A genetic test can now flag them, and the rare donors who could safely supply blood, before a crisis.

The MAL gene and a marker first described in 1972

Blood groups are defined by antigens, molecules on the surface of red cells that the immune system can recognise as foreign. The best known are ABO and Rh, but international committees list dozens of further systems, each with its own gene or genes. Most matter little day to day. They matter enormously for the patient whose immune system has learned to attack a common antigen that nearly every donor carries, because almost every unit of blood on the shelf is then incompatible.

AnWj was identified on red blood cells in 1972, yet its genetic basis stayed unknown. Tilley called the genetic background of AnWj a mystery of more than 50 years, one she had been trying to resolve for almost 20 years of her career, in the University of Bristol’s announcement. The work involved NHSBT’s Bristol laboratories, its International Blood Group Reference Laboratory (IBGRL) and the University of Bristol.

The team used whole exome sequencing on AnWj-negative individuals and found homozygous deletions in the MAL gene, which encodes a small membrane protein called Mal. The paper appeared in Blood, the journal of the American Society of Hematology, in 2024, with Tilley and Professor Ash Toye of the University of Bristol among the authors alongside Nicole Thornton of NHSBT and Tim Satchwell of UWE Bristol, as listed by Sci.News. The story circulated again in September 2026 through a ScienceDaily write-up of the NHSBT release.

Gene transfer experiment that confirmed the antigen

A deletion found in a few patients only suggests a link.

The decisive step was putting the normal MAL gene into laboratory cells that lacked it. Once that was done, the cells reacted with AnWj antibodies, which showed that the Mal protein carries the antigen. That experiment is what lets the International Society of Blood Transfusion treat MAL as a blood group system in its own right, number 47 on its list at the time.

Only five genetically AnWj-negative people were found during the study, among them members of an Arab-Israeli family, according to Interesting Engineering’s summary. That scarcity is the reason the puzzle lasted so long. More than 99.9% of people are AnWj-positive, so the inherited negative type shows up almost never, and when a patient turns up with an unexplained antibody there is rarely a family or donor panel to test against.

Safer transfusion for a handful of patients

Most AnWj-negative results in the clinic do not come from inheritance. Haematological disorders and certain cancers can suppress the antigen, which means a patient may become negative later in life and still carry the MAL gene intact. The new work separates those cases from the genetic one, because a deletion in both copies of the gene can be read directly from DNA.

That is the practical benefit, and it extends past the rare inherited cases to the larger group whose negative status is acquired, since a laboratory that can read the gene can tell at once which kind of patient it is dealing with and plan the blood supply accordingly. Genotyping can identify rare patients and donors, and a transfusion service can build a short list of compatible donors in advance rather than searching in an emergency. The Bristol statement makes the same point in plain terms: if people who are AnWj-negative receive AnWj-positive blood they could have a transfusion reaction.

Patients like this are usually found only after a crossmatch fails, which can delay surgery or treatment while staff search for blood that the patient’s antibody will not attack. A test that reads the MAL gene, or a donor register that records AnWj status, turns that scramble into a planned step, and it gives reference laboratories such as IBGRL a firm basis for confirming a suspected case rather than inferring it from serology alone.

The ScienceDaily account adds a 2026 case of a patient with lymphoma and anti-AnWj antibodies who was treated with the drug sutimlimab, an example of how complicated these cases remain even when the blood group is understood. The number that matters for planning is small: five genetically negative people in the original study, so every additional donor or patient that a MAL test identifies widens a very thin pool.

This article was produced with the assistance of AI and reviewed by Morning Overview editors prior to publication.

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