MAL blood group unveiled as a new player in the bank of blood group systems

by: Jan Pauline Roxas | Resistome

The presence of antigens determines the blood groups found on the surface of red blood cells. Some of the most well-known blood groups are the ABO and Rh systems, which are defined by the presence or absence of certain antigens. One example of a red blood cell antigen is the antigen AnWj or the Anton (ISBT 901009) high prevalence antigen, identified in 1972 and whose role was yet to be determined—not until it was linked as an entirely new genetic basis for a rare blood group: the MAL blood group.

Recent studies by British researchers working under the National Health Service Blood and Transplant in the UK and at the University of Bristol discovered that the antigen AnWj production occurs on a crucial Myelin and Lymphocyte protein (Mal), produced by the MAL gene. This gene encodes for the Mal proteolipid that regulates the presence of the AnWj antigen in red blood cells. 

Using advanced methods such as whole exome sequencing, the scientists have identified a genetic mutation in the MAL gene: a deletion that causes individuals with an inherited AnWj-negative phenotype to lack both the Mal protein and AnWj antigen. 

Individuals with the AnWj-negative phenotype may develop AnWj autoantibodies (anti-AnWj), which cause acute hemolytic transfusion reactions and act against the body’s own immune system by destroying the red blood cells given upon blood transfusion. On the other hand, the absence of the Mal protein itself does not appear to be directly associated with any pathological phenotype. This discovery allows for more accurate identification of AnWj-negative individuals, enhancing the safety of blood transfusions by improving consequent diagnostic tests. 

Senior researcher and contributor Louise Tilley explains that the discovery and establishment of the MAL blood group represents a huge achievement in solving the mystery of AnWj. The findings showcase important progress in the global understanding of blood genetics, paving the way for a new era of personalized medicine, especially for individuals with rare blood types.

SOURCES CITED

Englemed News. (2024, September 23). New Blood group solves half a century of mystery. British Society for Haematology . https://b-s-h.org.uk/about-us/news/new-blood-group-solves-half-a-century-of-mystery 

Tilley, L. A., Karamatic Crew, V., Mankelow, T. J., AlSubhi, S. A., Jones, B., Borowski, A., Yahalom, V., Finkel, L., Singleton, B. K., Walser, P. J., Toye, A. M., Satchwell, T. J., & Thornton, N. M. (2024). Deletions in the MAL gene result in loss of Mal protein, defining the rare inherited AnWj-negative blood group phenotype. Blood Journal. https://doi.org/10.1182/blood.2024025099

Xu, Z., Duffett, L., Tokessy, M., Cote, J., Goldman, M., & Saidenberg, E. (2012). Anti‐AnWj causing acute hemolytic transfusion reactions in a patient with aplastic anemia. Transfusion, 52(7), 1476–1481. https://doi.org/10.1111/j.1537-2995.2011.03477.x 

This article was originally published in GENEWS November 2024 Issue