According to researchers at NHS Blood and Transplant and the University of Bristol, scientists have successfully traced the genetic source of the rare AnWj blood antigen to the MAL gene, officially establishing MAL as the 47th human blood group system (ISBT 047) more than half a century after the marker was first encountered.
Tracing the AnWj Blood Antigen to the MAL Gene
According to NHS Blood and Transplant, the AnWj antigen was first discovered in 1972, yet for decades scientists lacked the knowledge of which gene produced it or which protein carried it on red blood cells. Over 99.9% of people test positive for AnWj, leaving a tiny minority of individuals who are AnWj negative. According to Louise Tilley, Senior Research Scientist, IBGRL Red Cell Reference at NHS Blood and Transplant, investigating the genetic background proved exceptionally difficult due to the scarcity of affected individuals. Researchers utilized whole exome sequencing to examine protein-coding DNA segments, which ultimately pointed unexpectedly to the MAL gene. Laboratory experiments confirmed that the gene produces a small membrane protein called Mal, which is both necessary and sufficient for expressing the AnWj antigen.
Did you know?
The AnWj antigen is named after the first people who made the antibody, Anton and Wj. While the ABO and Rh systems receive the most attention, the International Society of Blood Transfusion recognizes dozens of distinct blood group systems containing hundreds of antigens.
Why Inherited and Acquired AnWj Deficiency Matters for Transfusions
According to clinical findings, individuals can lack the AnWj antigen for two very different reasons. Most commonly, AnWj expression is suppressed due to an underlying hematological disorder or certain cancers, whereas a much rarer group of people are born without the antigen because of an inherited homozygous deletion affecting the MAL gene. According to published case reports from 2026, patients with acquired anti-AnWj autoantibodies face severe clinical complications. For instance, a 75-year-old man with severe anemia and an anti-AnWj autoantibody received unmatched red blood cells because compatible blood was unavailable. In another 2026 case involving a patient with high-grade B-cell lymphoma and a complement-binding anti-AnWj autoantibody, clinicians utilized sutimlimab—a drug that blocks part of the immune complement pathway—after incompatible transfusions triggered signs of red blood cell destruction.
New Genotyping Tools and the Expansion of Blood Group Systems
According to Nicole Thornton, Head of IBGRL Red Cell Reference at NHS Blood and Transplant, identifying the genetic basis of AnWj allows specialists to design targeted genotyping tests to identify rare patients and donors carrying relevant MAL changes. These diagnostic tools can be incorporated directly into existing blood group genotyping platforms. Ash Toye, Professor of Cell Biology in the School of Biochemistry and Director of the NIHR Blood and Transplant Research Unit in red cell products at the University of Bristol, noted that manipulating gene expression in developing blood cells was crucial to confirming the identity of the blood group. Following these findings, the International Society of Blood Transfusion formally reported MAL as ISBT 047 alongside other newly ratified systems such as ER, CD36, and ATP11C, further expanding the complex genetic map of human blood.
Frequently Asked Questions
What does it mean to be AnWj negative?
According to researchers, being AnWj negative means an individual lacks the AnWj red blood cell antigen. This condition can be caused either by a rare inherited genetic change in the MAL gene or, more frequently, by underlying health conditions like certain cancers or blood disorders.
How was the genetic source of AnWj discovered?
Scientists used whole exome sequencing to analyze DNA from rare affected individuals, discovering homozygous deletions in the MAL gene. Laboratory experiments subsequently proved that the Mal protein is necessary for the expression of the AnWj antigen.
Can inherited AnWj negative individuals live healthy lives?
Yes. According to researchers, people with the rare inherited form of MAL deletion are healthy, though finding compatible blood for transfusions can become challenging if they develop specific antibodies.
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