New Human Blood Group Identified After Scientists Solve Decades-Long Medical Mystery: Study - Video

A decades-old mystery in blood medicine has been solved with the identification of the MAL blood group system, helping explain why a small number of people lack the AnWj antigen and improving transfusion safety.

Researchers from NHS Blood and Transplant, the International Blood Group Reference Laboratory and the University of Bristol traced the genetic basis for AnWj, a marker first identified in 1972. The findings establish MAL as the 47th recognised blood group system and could help identify rare patients and donors through genetic testing.

More than 99.9% of people are AnWj positive. In the rare AnWj-negative group, antibodies against the antigen can attack transfused red blood cells, causing haemolytic transfusion reactions. AnWj can be absent because of certain blood disorders or cancers, but inherited absence is rarer.

The researchers studied five people with inherited AnWj-negative blood and used whole-exome sequencing to search for shared changes. They identified homozygous deletions affecting the MAL gene, which produces the Mal protein found on red blood cell membranes.

Laboratory experiments confirmed it. Introducing the normal MAL gene into cells caused them to react with AnWj antibodies, while the altered form did not. This showed that Mal is necessary and sufficient for AnWj expression.

The discovery has implications for transfusion medicine. Genetic tests can now be developed to identify people who inherit AnWj-negative blood, helping specialists locate compatible donors before an urgent transfusion.

The research also highlights that not all AnWj-negative cases have the same cause. People with normal MAL genes may lose AnWj expression because of underlying disease and develop antibodies.

The findings therefore provide a molecular explanation for this blood-group mystery that lasted more than 50 years, while offering a potential route to better identification and management of patients with rare transfusion needs.

REFERENCE: Louise A. Tilley, et al.; Deletions in the MAL gene result in loss of Mal protein, defining the rare inherited AnWj-negative blood group phenotype. Blood, 2024; 144 (26): 2735 DOI: 10.1182/blood.2024025099