A research team led by NHS Blood and Transplant scientists based in Bristol, at NHSBT’s International Blood Group Reference Laboratory (IBGRL), and supported by colleagues at the University of Bristol, has discovered a new blood group, MAL, solving a 50-year-old mystery.
The team identified the genetic background of the previously known but mysterious AnWj blood group antigen, thus allowing identification and treatment of rare patients lacking this blood group. Some people can lack this blood group due to the effect of illness, but the rare inherited form of the AnWj-negative phenotype has only been found in a handful of individuals – though due to this discovery it will now be easier to find others in the future.
The two best-known blood group systems are ABO and Rh but blood is more complex and matching across the other groups can be lifesaving. If people who are AnWj-negative receive AnWj-positive blood they could have a transfusion reaction. This research allows the development of new genotyping tests for detecting such rare individuals and reducing the risk of transfusion-associated complications.
The AnWj antigen was discovered in 1972 but its genetic background was unknown until now. The new research, to be published by Blood, the journal of the American Society of Hematology, and now available online in pre-print, establishes a new blood group system (MAL), the 47th ever to be discovered, as home to the AnWj antigen.
The research team established that AnWj is carried on the Mal protein. More than 99.9% of people are AnWj-positive, and such individuals were shown to express full-length Mal protein on their red cells, which was not present on the cells of AnWj-negative individuals. The team identified homozygous deletions in the MAL gene associated with the inherited AnWj-negative phenotype.
The most common reason for being AnWj-negative is due to suffering from a haematological disorder or some types of cancer which suppress antigen expression. Only a very small number of people are AnWj-negative due to a genetic cause. There were five genetically AnWj-negative individuals in the study including a family of Arab-Israelis. The blood tested included a sample given by a lady in 2015 who was the first AnWj-negative person to be discovered in the 1970s.
The research team used whole exome sequencing – the genetic sequencing of all DNA that encodes proteins – to show that these rare inherited cases were caused by homozygous DNA sequence deletions in the MAL gene, which codes for Mal protein.
Louise Tilley, Senior Research Scientist, IBGRL Red Cell Reference at NHS Blood and Transplant, said: “The genetic background of AnWj has been a mystery for more than 50 years, and one which I personally have been trying to resolve for almost 20 years of my career. It represents a huge achievement, and the culmination of a long team effort, to finally establish this new blood group system and be able to offer the best care to rare, but important, patients. The work was difficult because the genetic cases are very rare. We would not have achieved this without exome sequencing, as the gene we identified wasn’t an obvious candidate and little is known about Mal protein in red cells.”