Human Anatomy, Physiology, and Medicine. Anything human!
I read recently that an Australian teenager, Demi-Lee Brennan is the first known transplant patient to change blood groups with the transplant. Apparently she was originally an o-negative and changed to an o-positive following a liver transplant, after her body performed its own bone marrow transplant and adopted the donor's immune system. Because of this the girl will not have to tae anti-rejection drugs for the duration of her life...
So my questions are:
How is this possible?
Is it possible for a patient with this outcome, to have its body reject its own blood and organs in favour of a donor's?
What does liver damage do to the homeostatic mechanisms in the body?
What impacts would or should this case have on future science?
And how do the immune response systems assist us in survival and homeostasis?
Any help would be very much appreciated.
By O-negative/-positive, are we talking about the patient being Rh- and then becoming Rh+? Since the 'O' in ABO group means that the person simply does not express either A or B antigens - or does this mean that the person in question started to express one or both, A/B? It does have some relevance, because the A and B blood type antigens are very strong antigens, when compared to many other blood type antigens. This being said, also the rhesus factor is quite strong an antigen.
Whatever the case, at least with my current knowledge of haematology, I cannot quite see how this 'switch of blood type' could take place. The cells of the immune system are still in the person's body, and if this person's blood would change its blood type, a massive immunoreaction would take place against this new blood, ending up in massive hemolysis and death, I assume. The person would need more anti-rejection drugs than ever...
And about the actual mechanisms that would lead to the change of blood type: I guess that in _theory_, one could somehow acquire a haematologic stem cell that could settle in the bone marrow and start producing new cells with a different genotype (that's what is actually done with bone marrow transplantation, after all), but as far as I know, the existing lymphocytes will destroy any such cells (and normally destroy also the stem cell(s) itself) - unless the new cells are of identical or very similar MHC type, which then would not cause any kind of switch in the blood group either.
Now, a very far-fetched scenario might be the use of some kind of a cytotoxic drug that kills all the existing lymphocytes and then the foremention events might happen (in theory) without the new, different type cells being killed. Now of course, all the new lymphocytes that were somehow generated from the new stem cells, would be genetically mistmatched to the person's own tissues, which would probably cause problems with lymphocytes' self-tolerance (i.e. their ability to recognize host tissues as non-immunogenic).
Or, if the new stem cells only generated erythrocytes (and hence the "blood group" switch), then the person would lack all the immuno cells after this "cytotoxic" drug treatment that killed all the existing lymphocytes, and then the person would die in few days time unless they lived in a bubble for the rest of their lives.
So, either I forgot something crucial here, or the switch of blood group cannot happen, at least by any mechanism that I can think of at the moment. Maybe I have to try to find an article or something about this Brennan case in order to be able to speculate more
This seems to be an odd case, where the bone marrow may have died off and been regenerated by stem cells from the donor liver. It still seems like there's got to be some immunological problems down the road (will the new system see everything BUT the liver as foreign-?), but it's one of those things that aren't supposed to happen but did anyway. Welcome to biology...
Pretty amazing, I have to admit. Well, there are six billion of us, so apparently anything can happen
However, what comes to the details how this all actually happened, I think that article doesn't give an answer (i.e. what happened on the cellular/molecular level - what was her previous MHC haplotype and what is the new one, how do her original tissues deal with this "new immune system" and various other such details). I'm eager to see if they can come up with some kind of logical explanation, or if this really was "one in six billion" case. Either way, good for the girl herself, of course!
O.K. This article is better: http://abc.com.au/news/stories/2008/01/24/2146032.htm
Three things to note from the article:
1. Liver transplant
2. Rh incompatibility to donor
3. DNA virus infection
These are important because due to Rh incompatibility, she had to receive RhoGAM or MICRhoGAM to make sure she does not reject the liver. This drug, however, can in rare cases cause hemolytic reaction which can be helped by donor liver which suppose to “clean the blood”. Usually, this scenario leads to death, so the real question is why/how liver stem cells moved into bone marrow and why did her system get striped of immunity? Did the virus help?
Not directly related to the previous reply, but some people (myself included) thought about how the new immune system would recognize the original host tissue as own, and not launch an immune response against it.
This lead me to think that the explanation is probably the thymic selection, process that eliminates self-reactive T-lymphocytes in the thymus. This process isn't linked directly to genotype of the cells, but instead works based on the fact that self-reactive lymphocytes are removed from the repertoire regardless of their genotype (strictly speaking, some degree of self-reactivity remains in some cells, but that's another story). Therefore, the so-called positive and negative selection in the thymus should probably work for foreign T-cells as well, hence the the new system's tolerance to the original tissue types: only T-cells that recognize the original tissue type as "self" are allowed to survive in the thymus, just like in normal persons.
If she was Rh negative, she should receive immunoglobulins anti-D, but which dose and how often?
Cat, can you explain in depth the hemolytic reaction? I thought the hemolytic reation would take place only if you are Rhesus positive.
Hemolytic reaction is simply premature destruction of erythrocytes. It can occur for various reasons. One scenario is when Rh+ve baby gets attacked by mothers Abs (if she is Rh-ve). Some meds and toxins can cause this reaction as well though, it does not have anything to do with Rh factor in those cases.
I know what is a haemolytic reaction. What I want to know is how often she'd need anti-d
Yes, blood types change when there is total bone marrow ablation followed by donor cells which have a different blood type than the recipient's blood type. I am A+ and my donor is AB so I will be AB blood type after the bone marrrow transplant next month per Cleveland Clinic transplant nurse's information this is not a big deal and is not even on the 10/10 match parameters yet they would have liked same blood type in an ideal world. Mine is an unrelated donor yet many siblings are not the same blood type either.
My reason for bone marrow transplant: I have acute myelogenous leukemia. It is a diagnosis that is always a shock since a very healthy person may be golfing one day and the next day get labs telling them they have leukemia. Mine is like that. I've had 2 rounds of Ara-C, the first round also included idarubicin. These were to suppress the bone marrow and kill the leukemia. Both bone marrow biopsies were negative afterward but it will come back without a bone marrow transplant which is a huge risk yet can be curative. Risks include sepsis, graft vs host disease, etc. I am a nurse who recently became a physician which helps me understand all this yet it is complicated.
I was just briefly reading some comments the 1st comment actually got me to were i am now typing on here. To cut a long story short when i was 10 back in 1996 i was diagnosed with Leukeamia (A.L.L) and was in remission for 5 yrs then had a relaps with exactly the same condition in 2001 at age 15 my blood type being A+. I underwent a bone marrow transplant, my donor was my little sister we were 99.99% compatible and her blood type being O+. 10 years August 29 this year 2011 i will be celebrating my 10th bday (but i am really 25) as the owner of O+ blood. So in my book my blood group changed before the girl that had the liver transplant, though it was under different circumstances i think it still counts.
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