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Newly Discovered Blood Group System to Help Identify and Treat Rare Patients

By LabMedica International staff writers
Posted on 18 Sep 2024

The AnWj blood group antigen, a surface marker discovered in 1972, has remained a mystery regarding its genetic origin—until now. More...

The most common cause of being AnWj-negative is linked to hematological disorders or certain types of cancer that suppress antigen expression. However, only a very small number of individuals are AnWj-negative due to genetic factors. While ABO and Rh are the most well-known blood group systems, blood matching across less familiar groups, such as AnWj, can be critical for saving lives. Individuals who are AnWj-negative risk a transfusion reaction if they receive AnWj-positive blood. Researchers have now uncovered the genetic background of the AnWj antigen, enabling the identification and treatment of rare patients who lack this blood group. This discovery paves the way for the development of new genotyping tests to detect individuals with the inherited AnWj-negative phenotype, reducing the risk of complications from blood transfusions.

The research, led by investigators from the University of Bristol (Bristol, UK), has identified a new blood group system, MAL, the 47th known system, as the home of the AnWj antigen. The team discovered that the AnWj antigen is carried on the Mal protein. More than 99.9% of people are AnWj-positive, with those individuals expressing full-length Mal protein on their red blood cells. In contrast, this protein was absent in the cells of AnWj-negative individuals. The study identified homozygous deletions in the MAL gene associated with the inherited AnWj-negative phenotype. Among the participants were five genetically AnWj-negative individuals, including a family of Arab-Israelis. One of the blood samples tested was from a woman who had first been identified as AnWj-negative in the 1970s.

The researchers employed whole exome sequencing, which analyzes the protein-coding regions of DNA, to demonstrate that these rare inherited cases were caused by homozygous deletions in the MAL gene, which encodes the Mal protein. They confirmed that Mal is responsible for binding AnWj antibodies from these rare patients through experiments that showed specific reactivity with cells containing the normal MAL gene, but not the mutant gene. The findings of this research were published in the journal Blood.

“Resolving the genetic basis for AnWj has been one of our most challenging projects. There is so much work that goes into proving that a gene does actually encode a blood group antigen, but it is what we are passionate about, making these discoveries for the benefit of rare patients around the world,” said Nicole Thornton, Head of IBGRL Red Cell Reference at NHS Blood and Transplant, which was a part of the research group. “Now genotyping tests can be designed to identify genetically AnWj-negative patients and donors. Such tests can be added to the existing genotyping platforms.”


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