Feb 8, 2010 - Research

Genetic Variant Involved in Dangerous Blood Transfusion Reaction Identified

There’s no doubt that blood saves lives.   According to the Red Cross, in the United States alone about five million people need a total of 14 million pints of blood each year.   That’s 38,000 pints every day.

But transfusions are not without their dangers.   Among them is transfusion-related acute lung injury (TRALI), a rare but potentially life-threatening condition that happens when there is a clash between donor and recipient blood.   TRALI is one of the major causes of transfusion-association deaths in the developed world.

New research, recently published in the journal Nature Medicine, suggests that many cases of TRALI are due to a difference at just one genetic variation between donor and recipient.   This finding could someday enable screening before a transfusion is done, allowing doctors to reduce the risk of TRALI.

One reason TRALI happens is that a donor’s blood contains antibodies that recognize something in the recipient’s blood as an enemy.   These donor antibodies mount an attack that sets off a chain reaction of immune responses in the recipient’s body, leading to lung injury.   Several triggers for this type of TRALI have been identified.   One of these, the HNA-3 antigen, has repeatedly been associated with severe and fatal TRALI reactions.

HNA-3 comes in two versions: HNA-3a and HNA-3b.   A person whose body expresses only the HNA-3a version can make antibodies against the HNA-3b version if he or she is exposed to it somehow.   Likewise, a person whose body expresses only the HNA-3b version of the protein can end up with antibodies against the HNA-3a version. Someone who expresses both HNA-3a and HNA-3b, as a result of inheriting a different version from each parent, won’t make antibodies against either version.   For reasons that aren’t really understood, only antibodies against the HNA-3a version are relevant when it comes to TRALI.

The most common route of exposure to foreign versions of the HNA-3 antigen is childbirth.   A woman can be exposed to her child’s blood, and if it contains a different version of HNA-3 than her body is used to, she might produce antibodies.   The likelihood that a woman will have antibodies against HNA-3 increases with each birth.

The authors of the new study suggest that their new findings can be used to develop a large-scale screening program that could reduce the risk of TRALI.   Blood donors could be genetically screened to find those who are capable of producing antibodies against HNA-3a (i.e., they are AA at ).   Alternatively, the new genetic information could help scientists create artificial HNA-3a antigens that could be used in the lab to screen donated blood directly.

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