Solving a Blood-Type Mystery
BRYAN BALLIF, PH.D., ASSOCIATE PROFESSOR OF BIOLOGY
In the early 1950's, a 66-year-old woman, sick with colon cancer, received a blood transfusion. Then, unexpectedly, she suffered a severe rejection of the transfused blood. Reporting on her case, the French medical journal Revue D'Hématologie identified her as, simply, "Patient Vel." After a previous transfusion, it turns out, Mrs. Vel had developed a potent antibody against some unknown molecule found on the red blood cells of most people in the world — but not found on her own red blood cells.
But what was this molecule? Nobody could find it. A blood mystery began, and, from her case, a new blood type, "Vel-negative," was described in 1952. Though rare, it is estimated now that more than 200,000 people in Europe and a similar number in North America are Vel-negative, about 1 in 2,500. For these people, successive blood transfusions could easily turn to kidney failure and death. So, for sixty years, doctors and researchers have hunted — unsuccessfully — for the underlying cause of this blood type.
Now a team of scientists including UVM biologist Brian Ballif, Ph.D., has found the missing molecule — a tiny protein called SMIM1 — and the mystery is solved. Reporting in the journal EMBO Molecular Medicine, Ballif, Lionel Arnaud of the French National Institute of Blood Transfusion, and their colleagues explain how they uncovered the biochemical and genetic basis of Vel-negative blood. Previously, Ballif and Arnaud identified the proteins responsible for two other rare blood types, Junior and Langeris, moving the global count of understood blood types or systems from 30 to 32. With Vel, the number rises to 33.
Before this new research, the only way to determine if someone was Vel-negative or positive was with tests using antibodies made by the few people previously identified as Vel-negative following their rejection of transfused blood. Not surprisingly, these antibodies are vanishingly rare and, therefore, many hospitals and blood banks don't have the capacity to test for this blood type. Ballif notes that Vel-negative blood is one of the most difficult blood types to supply in many countries, partly due to the rarity of the Vel-negative blood type, but also to the lack of systematic screening for the Vel-negative type in blood donors.
In response, the UVM and Paris researchers developed two fast DNA-based tests for identifying Vel-negative blood and people. These tests can be easily integrated into existing blood testing procedures — and can be completed in a few hours or less. "It's usually a crisis when you need a transfusion," says Ballif. "For those rare Vel-negative individuals in need of a blood transfusion, this is a potentially life-saving timeframe."
To make their discovery, the team in Paris used some of the rare Vel-negative antibody to biochemically purify the mystery protein from the surface of human red blood cells. Then they shipped them to Ballif in Vermont. The little protein didn't reveal its identity easily, and Ballif had to sort through thousands of proteins. After several experiments failed to find the culprit because of its unusual biochemistry and pipsqueak size, success came with the use of a high-resolution mass spectrometer funded by the Vermont Genetics Network.
Today, personalized medicine — where doctors treat us based on our unique biological makeup — is on the rise. "The science of blood transfusion has been attempting personalized medicine since its inception," Ballif notes, "given that its goal is to personalize a transfusion by making the best match possible between donor and recipient. Identifying and making available rare blood types such as Vel-negative blood brings us closer to a goal of personalized medicine."
With this new discovery, even that rare one person out of 2,500 that is Vel-negative has a way to receive a rapid blood-typing should they need a transfusion.
Last modified May 19 2014 03:59 PM