SNPwatch: 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 new research found that the different versions of HNA-3 are due to SNP rs2288904 in the SLC44A2 gene.  Someone who is GG at this SNP will express only HNA-3a.  Someone who is AG will express both the HNA-3a and HNA-3b version.  Finally, someone who is AA at rs2288904 will express only HNA-3b.  The first two genotypes (GG and AG) represent about 95% of the population with European ancestry.  These are the people who are at risk for TRALI if they receive blood from a donor who is part of the 5% of the population that has AA at rs2288904.

(23andMe Complete Edition customers can check their data for rs2288904 using the Browse Raw Data feature.)

Confused?  Here’s an example from my own family that will hopefully make things more clear:

My mom is AA at rs2288904, meaning that her body expresses only HNA-3b.  My brother and I are both AG  (we inherited the G at this SNP from my father), so we have both HNA-3a and HNA-3b in our bodies.  If my mom was exposed to blood from my brother and/or me while we were being born, her immune system could have recognized our HNA-3a antigens as foreign and made antibodies.  So now, if my mom gave blood to my brother or me, we would be at risk for TRALI, even though we all have the same ABO blood type (A+).
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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 rs2288904).  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.

SNPwatch gives you the latest news about research linking various traits and conditions to individual genetic variations. These studies are exciting because they offer a glimpse into how genetics may affect our bodies and health; but in most cases, more work is needed before this research can provide information of value to individuals. For that reason it is important to remember that like all information we provide, the studies we describe in SNPwatch are for research and educational purposes only. SNPwatch is not intended to be a substitute for professional medical advice; you should always seek the advice of your physician or other appropriate healthcare professional with any questions you may have regarding diagnosis, cure, treatment or prevention of any disease or other medical condition.


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