After fifty years of mystery and painstaking research, a team of scientists from the UK and Israel have solved the mystery of the rare blood type AnWj. This advance not only reveals its genetic origins, but also introduces a new blood group system, MAL, which becomes the 47th classification system to be identified to date.
The finding, made possible by a collaboration between researchers from NHS Blood and Transplant, the NHSBT International Blood Group Reference Laboratory (IBGRL) and the University of Bristol, will improve the identification and treatment of patients with this rare disease who, if given an incompatible blood transfusion, may face serious complications.
50 years of intrigue
The AnWj antigen was first identified in 1972, when doctors, while analyzing the blood of a pregnant woman, noticed the absence of a surface molecule present in all red blood cells known up to that time. Since then, the genetic cause of this peculiarity has remained hidden and has become an interesting challenge for scientists. Now this new study, which will be published in the Journal of the American Society of Hematology Blood, found that the AnWj antigen is carried in the Mal protein and its presence or absence is caused by specific genetic variations.
Louise Tilley, IBGRL Senior Researcher, has dedicated nearly 20 years of her career to unraveling this mystery. “The genetic origin of AnWj has been a mystery for more than 50 years,” Tilley comments in a press release. “To finally create this new blood grouping system and be able to offer the best care to rare patients is a great achievement and the culmination of a long team’s work,” he added.
The key to success was the use of whole-exome sequencing, a technique that made it possible to analyze protein-coding DNA. This revealed that a mutation in the MAL gene is responsible for the lack of AnWj antigen in some patients.
But what does this mean for ordinary people? Although more than 99.9% of people are AnWj positive, those rare individuals who are AnWj negative may suffer severe reactions if they receive an incompatible blood transfusion due to homozygous deletions in the MAL gene. The new discovery makes it possible to develop genotyping tests to identify these rare patients and reduce the risk of complications.
For the ABO and Rh blood group systems
Although most of us are familiar with the ABO and Rh blood group systems, there are actually many more, based on the different proteins and sugars that make up our red blood cells. These antigens act as identification markers for the body to distinguish between “self” and “foreign”. If these markers do not match during a transfusion, an adverse or even fatal reaction can result.
Although most AnWj-negative people are thus caused by hematological disorders or certain types of cancer that suppress antigen expression, the study identified five individuals with an inherited form of this phenotype, including an Arab-Israeli family and the first patient discovered in the 1970s.
“It is really exciting that we have been able to use our ability to manipulate gene expression during the development of blood cells to help confirm the identity of the AnWj blood group, which has been an outstanding mystery for half a century,” said Professor Ash Toye from the University of Bristol.
This discovery not only satisfies scientific curiosity, but also has significant practical implications. Nicole Thornton, Head of Red Blood Cell Reference at IBGRL, said genotyping tests could now be designed to identify patients and donors genetically negative for AnWj, which could save lives in the future.
Edited by Felipe Espinosa Wang with input from the University of Bristol, Blood and Science Alert.
