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Characterization of the molecular cause of the most frequent fatal transfusion reaction will make blood transfusion safe

28.12.2009 - (idw) Ernst-Moritz-Arndt-Universität Greifswald

Researchers at Greifswald University and of the German Red Cross Transfusion Service West achieved a breakthrough in improving safety of blood transfusion, reporting today in the high impact journal "Nature Medicine" (www.nature.com). The Greifswald transfusion medicine group from the laboratory of Prof. Andreas Greinacher and the functional genomics laboratory of Prof. Uwe Völker, together with the leukocyte immunology laboratory, German Red Cross Blood Service West under the leadership of Prof Jürgen Bux and Dr Angelika Reil, discovered and characterized a "blood group"on white blood cells, responsible for causing the most frequent fatal reaction after blood transfusion in the western world.

"This discovery will be instrumental to prevent transfusion associated acute lung injury (TRALI)", said Prof. Andreas Greinacher, head of transfusion medicine at Greifswald University.
The risk for the adverse reaction TRALI after blood transfusion is currently much higher than the risk of transmitting HIV or hepatitis-C by blood products. The major cause of severe and life-threatening TRALI is antibodies unexpectedly found in the blood of the blood donor. These antibodies are transfused with the blood to the patient and bind to a blood group protein on the white blood cells (granulocytes). This causes the white blood cells to form aggregates ("clumps") which block the small blood vessels within the lungs. The lung tissue becomes injured and pulmonary edema ("fluid in the lungs") causes respiratory failure and sometimes death.
The blood donors who carry these antibodies in their blood are perfectly healthy, the antibodies are not harmful to the blood donor, who is unaware of their presence. They are only dangerous if transfused into a patient. This important discovery of the researchers from the University of Greifswald and the German Red Cross Blood Service West will permit screening of blood donors for these antibodies, and will result in exclusion of these potentially dangerous units of blood from entering the blood supply, thereby preventing a major cause of transfusion-associated death.

For many years, several research groups throughout the world have sought to characterize this "missing blood group" on white blood cells. After three years of intensive laboratory work, the German research groups had now been successful. To characterize the missing blood group, they isolated large amounts of white blood cells from the blood of healthy blood donors, and then used these dangerous antibodies to "fish" for the missing protein, using molecular biology methods, and thereby were able to purify the protein bearing this dangerous blood group. After identifying several amino acids of this protein they could track the gene using the data base of the human genome project. Next, they inserted this gene into bacteria. These transfected bacteria now produced the blood group protein in large quantities. This recombinant protein is the basis for developing tests for preventive screening of blood donors.

The Greifswald University in the very North-East of Germany has become one of the most popular medical schools in the country. The life science research campus of the University has been funded with several million Euro by the German Ministry for Education and Research (Bundesministerium für Bildung und Forschung), and has become an internationally recognized centre of research excellence, especially the centres for "functional genomics" (www.medizin.uni-greifswald.de/fungene) and for "immune reactions in cardiovascular disease" (www.hike-autoimmunity.de). For the German Red Cross Transfusion Service West, this work is another success in their efforts to improve blood safety, an effort underway since 2006 to reduce the risk of TRALI.

Article (NMED-BC44834D) in "Nature Medicine", December 27, 2009 (online)
December 2009, Volume 15 No 12
"Characterization of the human neutrophil alloantigen (HNA) 3a"
http://www.nature.com/nm/journal/vaop/ncurrent/full/nm.2070.html

Contact
Universitätsklinikum Greifswald
Institut für Immunologie und Transfusionsmedizin/Abteilung Transfusionsmedizin
Prof. Dr. med. Andreas Greinacher
Sauerbruchstraße, 17475 Greifswald
T + 49 3834 86-5479
greinach@uni-greifswald.de

www.klinikum.uni-greifswald.de
Weitere Informationen: http://www.nature.com/nm/journal/vaop/ncurrent/full/nm.2070.html - article in "Nature Medicine", December 27, 2009 (online) http://www.medizin.uni-greifswald.de/fungene - centre for "functional genomics" http://www.hike-autoimmunity.de - for "immune reactions in cardiovascular disease"
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