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A case fit for House MD

imageI’m a huge fan of the show House MD. In particular, I love the show’s use of incredibly bizarre, but true medical cases. For example, in one of the earlier shows, House and his team make a diagnosis based on the fact that sleeping sickness can be transmitted by sexual contact. That may sound like nothing extraordinary, until it becomes emphasized that this medical “fact” is actually one reported case in a foreign medical journal. Probable? No. But, fake? Not really.

Unfortunately, consulting does not leave much time in my day for keeping up with scientific papers. I end up accumulating a pile of papers to read which just never seems to shrink. However, I was recently shook from my paper-reading stupor when A. Phan pointed me to one particularly interesting study published in the most recent issue of the New England Journal of Medicine. The AFP article which summarizes the study is simply jaw-dropping:

Girl switches blood type after liver transplant

The medical study details the struggles of a 9 year old Australian girl who needed a liver transplant due to a case of “non-A-to-G hepatitis” (translation: doctors know that something serious is hitting the liver, but they have no clear idea what it is). She is given a liver transplant from a 12 year old boy who died of hypoxia (lack of oxygen to the brain) and is positive for a normally innocuous virus called CMV (cytomegalovirus). The match is nowhere near perfect, so the girl is treated with immunosuppressants to prevent rejection.

Unfortunately, while CMV is normally harmless, it can cause problems in patients with weakened immune systems. Sure enough, the girl had to be re-admitted to the hospital 2 weeks after being discharged. Her doctors noted that the severe lymphopenia (a shortage of the blood cells needed to fight infection) that was ailing the girl prior to the transplant had persisted even 5 weeks after the transplant. The doctors had simply thought this was a combination of infection and the immunosuppressants they were giving her, so they adjusted the medication they gave her.

7-8 months after that (9 months post-liver transplant), the girl was re-admitted to the hospital for surgery due to a bowel obstruction, and it was then that they noticed that the patient’s blood, which had previously been type O-negative, had tested O-positive! This was especially incredible given that both parents were homozygous O-negative, meaning that there was no way, genetically, that the girl could produce O-positive blood. Typically, the only way a blood type switch happen is through a bone marrow transplant, which replaces the blood-making cells of our bodies with the blood-making cells from a donor — and even then, it’s accompanied by something which the girl did not suffer from called GVHD (Graft-Versus-Host Disease), where the new donor immune system thinks that the recipient’s entire body is foreign, and should thus be attacked.

image A month after that (10 months post-liver transplant), after a mild respiratory tract infection (a cold or cough), the girl started showing signs of hemolytic anemia. Literally, her blood cells were bursting — something you would expect in blood type mismatch problems. Heavy immunosuppressive therapy and constant transfusions seemed only to alleviate the problem slightly. A careful examination of her blood showed that her immune cells were more than 90% from the donor, something which was verified not only by blood type, but also by the fact that these cells had Y chromosomes (results from fluorescence in-situ hybridization to the right; red dot is a Y chromosome; green dot is a X chromosome; the cell at the top is thus XX — female — and the cell at the bottom right is XY — female).

In words that President George W. Bush might understand, the donor’s new blood cells are US forces in Iraq. The remaining blood cells from the girl are scared Iraqi’s who see strangers everywhere and are prone to using guns. The hemolytic anemia is the result of the ensuing fighting. And the immunosuppresants are some magical way (maybe supplying both sides with alcohol?) to reduce the ability of both sides to fight.

The doctors had a choice. Do they:

  1. Give her a drug to wipe out a big chunk of the immune cells from both donor and recipient (nuke Iraq to kill enough people, on both sides, to stop the war)
  2. Stop all immunosuppressants and just let the immune cells duke it out (take off all the handcuffs on US forces and let them wipe out the remaining Iraqi insurgents and hope that Iraq is still in one piece when it’s all over)

They went with the second strategy.

It is now about 5 years after the transplant. The girl is healthy, and no longer on immunosuppressants. Her blood is now completely from the donor, despite the lack of bone marrow transplant. There has been no sign of the GVHD which typically accompanies the sorts of bone marrow transplants which could lead to blood type switching, and it would appear that the girl’s new immune system has been “re-trained” to not recognize the liver or the girl’s body as foreign.

So, the big question in my mind is how? How could a non-bone marrow transplant lead to blood type switching? The only two things I can think of are:

  1. A virus caused liver cells from the transplant to fuse with the girl’s blood-making bone marrow cells. Why it may be possible:
    1. In biology labs, forcing cells to fuse is oftentimes done with viruses
    2. It is known that stem cells like the blood-making bone marrow cells are prone to fusing (a result which confused many early researchers who were positive they found examples of blood stem cells turning into non-blood cells)
  2. Because the boy was so young, it is possible that the transplanted liver still contained blood-making stem cells which were re-activated. Why it may be possible:
    1. The fetal blood supply is produced, at least in part, by cells in the liver
    2. Stem cells which are dormant (e.g. the cells in your skin that can produce new skin) can be activated with the appropriate stimuli (e.g. burn)

This is all just speculation on my part, and I doubt we will ever find the answer in the case of this patient (who is no doubt sick of doctors and hospitals), but things like this are reasons why I love House and why I love science.

Published in Blog

2 Comments

  1. […] little over two years ago, I blogged on a very interesting New England Journal of Medicine paper about a bizarre medical case where a […]

  2. […] a big fan of House, not only because the lead character is someone we all (or maybe just me) wish we could be (someone […]

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