For over 30 years, a peculiar case of blood with an unknown antigen puzzled scientists. In 1972, a pregnant woman’s blood sample revealed a missing surface marker, crucial for blood typing, sparking a decades-long mystery. That enigmatic antigen, now identified as AnWj, has been the subject of a recent breakthrough by Louise Tilley and her team at NHS Blood and Transplant.
Unveiling the AnWj Blood Group System
The journey to uncover the genetic basis of AnWj-negative blood, a rare blood type with fewer than tens of thousands of cases globally, has been arduous. The discovery of this blood group system, the 47th recognized by scientists, adds to the complex classification of human blood types, including the well-known ABO and Rh systems.
Louise Tilley, who joined NHS Blood and Transplant in the early 2000s, was tasked with solving this mystery. Initial expectations of a straightforward solution soon gave way to a prolonged investigation. It took Tilley and her colleagues 19 years to identify the genetic anomaly responsible for the AnWj-negative blood type. Their findings were published in the journal Blood, marking a significant milestone in hematology.
The Genetic Breakthrough
The antigen in question, AnWj, was named after two individuals known to lack this surface marker. Most people have AnWj-positive blood, but AnWj-negative individuals are exceptionally rare. Nicole Thornton, a co-author of the study, highlights the critical importance of identifying this rare blood type for medical safety, especially for those requiring blood transfusions.
The research team’s breakthrough came through extensive genetic sequencing, focusing on the MAL gene, which plays a crucial role in blood cell function. They discovered that individuals with AnWj-negative blood shared a unique mutation in the MAL gene. This finding was pivotal in explaining why certain individuals lacked the AnWj antigen on their red blood cells.
The study encountered challenges, including competing research suggesting an alternative gene. Despite initial setbacks, Tilley and her team persevered, eventually proving the MAL gene’s role in determining the AnWj blood type. They demonstrated that introducing a functional MAL gene into AnWj-negative cells could restore the antigen, confirming their hypothesis.
Implications and Future Research
The identification of the MAL gene’s role in AnWj-negative blood has practical implications for blood donation and transfusion compatibility. Understanding this genetic basis will help locate potential donors with AnWj-negative blood and ensure safe transfusions for those affected.
The discovery contributes to a broader understanding of blood group systems and complements previous work by Tilley’s team on other blood group systems, such as the Er system in 2022 and the MAM system in 2020. As blood researchers continue to explore new systems, more blood-related mysteries await resolution.
Experts like Sara Trompeter and Mark Vickers praise the meticulous work of Tilley and her colleagues, noting the significance of their findings for the field of hematology. The discovery underscores the importance of continued research in solving complex medical puzzles.
The study also opens avenues for further investigation, particularly regarding why the AnWj antigen appears only after birth and its potential links to other genetic or environmental factors.
References:
https://pubmed.ncbi.nlm.nih.gov/29956848/
https://www.researchgate.net/publication/223990805_Persistent_complement-dependent_anti-AnWj_in_a_lymphoproliferative_disorder_A_case_study_and_review
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(Rehash/Ankur Deka/MSM)
