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Science

Teen Takes On Donor's Immune System 231

Posted by Zonk
from the you-will-be-assimilated dept.
Leibel writes "The Australian ABC News is reporting that a 15-year-old Australian liver transplant patient has defied modern medicine by taking on her donor's immune system. Demi-Lee Brennan had a liver transplant. Nine months later, doctors at Sydney's Westmead Children's Hospital were amazed to find the teenager's blood group had changed to the donor's blood type. They were even more surprised when they found the girl's immune system had almost totally been replaced by that of the donor, meaning she no longer had to take anti-rejection drugs. 'Dr. Michael Stormon says his team is now trying to identify how the phenomenon happened and whether it can be replicated. "That's probably easier said than done... I think it's a long shot," he said. "I think it's a unique system of events whereby this happened. "We postulate there's a number of different issues - the type of liver failure that she had, some of the drugs that we use early on to suppress the immune system and also that she suffered an infection with a virus called CMV, or cytomegalovirus, which can also suppress the immune system."'"
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Teen Takes On Donor's Immune System

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  • ob. (Score:5, Funny)

    by russellh (547685) on Thursday January 24, 2008 @01:40PM (#22169650) Homepage
    kids these days.
  • by Anonymous Coward on Thursday January 24, 2008 @01:41PM (#22169676)
    Kill her! Who knows what other powers she might have?
  • by KublaiKhan (522918) on Thursday January 24, 2008 @01:43PM (#22169728) Homepage Journal
    Sounds like carbosilicate amorph warfare to me...but then, who'dathunk that the Australians would go in for that schlock?

    Actually, if memory serves, NPR had a short bit on a treatment for negating the need for anti-rejection drugs in kidney transplants--they not only transplanted the kidney, but also bone marrow from the donor, and 5 patients out of 6 were able to go off the anti-rejection drugs.
    • by Jesus_666 (702802)

      Sounds like carbosilicate amorph warfare to me...but then, who'dathunk that the Australians would go in for that schlock?
      Sounds like an illegally modified cryokit to me. People, watch out for exploding secretions.
  • Self-rejection? (Score:5, Interesting)

    by Anonymous Coward on Thursday January 24, 2008 @01:47PM (#22169778)
    So if she takes on her donor's immune system, how does that prevent her from rejecting her own body tissues?
    • Re: (Score:2, Funny)

      by xSauronx (608805)
      maybe the tissues are unionized?
    • by KublaiKhan (522918) on Thursday January 24, 2008 @01:56PM (#22169952) Homepage Journal
      Perhaps it has something to do with the virus she caught--it suppressed the immune system to the point where it had to 'reboot', as it were, and apparently recognized the new hardware on boot?

      Which would seem to indicate that the immune system BIOS has some kind of PnP support--I guess that'd explain some of the viruses...
      • by Anonymous Coward on Thursday January 24, 2008 @01:57PM (#22169974)
        What the hell kind of car analogy is that?
        • Re: (Score:3, Funny)

          by IdeaMan (216340)
          Dude... "Get out of the car, get back in the car." It's a classic.

          Haven't heard it before? Here goes:
          A mechanical engineer, hydraulic engineer, electrical engineer and a computer programmer were riding together in the car, and it stops. They all get out and look at the car. The mechanical engineer checks the tires, the hydraulic engineer checks the brakes, and the electrical engineer checks the voltage on the battery. The computer programmer goes "Guys cmon, all we gotta do is get out of the car and ge
          • so that's the purpose of Chinese fire drills.
        • by ozbird (127571)
          She had non-genuine parts fitted, but didn't void her new car warranty?
      • by Arthur B. (806360)
        Best hypothesis I read so far.
      • Being a wireless guy the first thing I thought of is the way the 802.11 IBSS protocol merges ad-hoc cells.
      • BSOD (Score:2, Funny)

        by einnar2000 (985070)

        Perhaps it has something to do with the virus she caught--it suppressed the immune system to the point where it had to 'reboot', as it were, and apparently recognized the new hardware on boot? Which would seem to indicate that the immune system BIOS has some kind of PnP support--I guess that'd explain some of the viruses...
        A BSOD would truly suck on this type of reboot.
    • by Firethorn (177587)
      It's more likely a hybrid immune system at this point. So both body tissue types are accepted.
      • Re:Self-rejection? (Score:5, Informative)

        by NIckGorton (974753) on Thursday January 24, 2008 @02:18PM (#22170332)
        Nope. Its the boy's immune system now. From the NEJM article:

        "The change in this patient from group O, RhD-negative blood to group O, RhD-positive blood suggested the development of chimerism by engraftment of the recipient marrow from passenger hematopoietic stem cells within the transplanted liver. Fluorescence in situ hybridization studies for the X and Y chromosomes were performed on a bone marrow aspirate and peripheral-blood lymphocytes 3 months after the onset of hemolysis (post-transplantation day 395).2 Analysis of cells from the marrow, sorted by means of flow cytometry, showed that they were male (XY) in myeloid, erythroid, and CD19+ B cells. Analysis of peripheral-blood aliquots revealed a predominantly male (donor) population: of 50 T cells, 94% were male and 6% were female; of 50 B cells, 98% were male and 2% were female; of 50 granulocytes, 100% were male; and of 50 natural killer cells, 100% were male"
        And that was while she was still on an immune suppression regimen. After they found the results above, they made a decision: "These results suggested that the hemolysis was due to the production of antibodies by residual B lymphocytes in the recipient against engrafted erythroid cells from the donor. A choice between two therapeutic options was then considered: the use of rituximab, an anti-CD20 monoclonal antibody, which would deplete all B cells (both host and donor cells), or withdrawal of all immunosuppressive therapy to allow full engraftment. The decision was made to withdraw the immunosuppressive therapy." After which her immune system essentially became entirely that of the boy whose liver she received. Even to the point that since he hadn't gotten his MMR vaccine, she lost her immunity to measles, mumps, and rubella (which she regained when she was re-immunized.)
    • Re:Self-rejection? (Score:5, Insightful)

      by AgentPaper (968688) * on Thursday January 24, 2008 @02:19PM (#22170350)
      That was precisely my thought - where exactly does this differ from GVH? [wikipedia.org] Any time you have a mismatch between HLA haplotypes on immune cells and other tissue cells, you're going to have an immune reaction, regardless of whose immune cells initiate it. It's rather unique that this occurred in the context of a solid organ transplant - you usually see it with bone marrow - but the underlying process doesn't look any different.

      Of course, ABC News isn't exactly a peer-reviewed journal, so I'll reserve full analysis for such time as this patient is written up in the literature, but I'm not seeing anything outside the realms of modern medicine here.

    • Re:Self-rejection? (Score:4, Interesting)

      by barakn (641218) on Thursday January 24, 2008 @04:46PM (#22172758)
      What everyone seems to be missing and what is so cool about this case is that it was [b]stem cells[/b] that migrated to the bone marrow. These stem cells were in an untrained state. Once they differentiated into B cells, T cells, macrophages, etc., they went through the same training process that happened to you as an infant, where any self-reactive cells are programmed to self destruct. It really was a full reboot.
  • by G3ckoG33k (647276) on Thursday January 24, 2008 @01:48PM (#22169794)
    Is she related to Sigorney Weaver? That may have unexpected consequences, in the long run. What was the name of the company treating the girl again?
  • by kindbud (90044) on Thursday January 24, 2008 @01:50PM (#22169832) Homepage
    Wouldn't her new immune system see the rest of her body apart from the liver as a foreign invader, and attack it?
    • by Asmor (775910)
      That was my initial thought as well.
    • by NIckGorton (974753) on Thursday January 24, 2008 @02:06PM (#22170126)
      Yes, its called Graft Versus Host Disease (GVDH), and is a common complication of bone marrow transplantation. If it happens, it manifests as skin, liver, and gut problems mostly. Liver obviously isn't going to be a problem for her, and it sounds like from the original NEJM article I just read that she hasn't had any other manifestations of GVHD. If you are going to get bad GVHD its usually early on, so she's out of that woods, but there is always chronic GVHD manifestations that will show with time.

      Though given a choice, I'd take the GVHD risk, lose the immunosuppressants, and never worry that my liver graft would fail. All in all she's a hella lucky kid.
      • Hopefully, they'll study what happened in depth (without treating the kid as a lab experiment). I'm not a bioengineer, but could you determine what caused this and make tailored immune systems for people who either never had a good one through birth defect or lost theirs to HIV/AIDS?
  • With these developments, it's my hope that more good news will come by. Let me hope that the recipient will not eventually "inherit" the donor's "bad" or weak characteristics. What about DNA? Suppose that the recipient's DNA changes to the donor's?
    • What about DNA? Suppose that the recipient's DNA changes to the donor's?


      I really don't see that happening. The best along that line that you could hope for would be a mild to moderate case of chimerism [wikipedia.org].
    • by Jerf (17166)

      What about DNA? Suppose that the recipient's DNA changes to the donor's?
      What if magic is real and the liver donor curses the recipient from beyond the grave?

      It's about as likely.
  • IYes, I read TFA (Score:4, Interesting)

    by Ethanol-fueled (1125189) on Thursday January 24, 2008 @01:51PM (#22169846) Homepage Journal
    ...and the two most interesting words in it were "...stem cells..."
    • by halivar (535827)
      They're talking about adult stem cells, which are not very interesting because there's no political disagreement about them.
  • After 18 months she turned into a clone of the 50 year old male liver donor. Doctor's response, "hey at least the liver works".
    • Re: (Score:3, Funny)

      by LinuxGeek (6139) *
      And now she is finding that she lusts after herself.
      • Re: (Score:3, Interesting)

        by TheLink (130905)
        Actually that might happen.

        There have been anecdotal (yeah I know) accounts of people receiving transplants and then having personality changes - food preferences or even sexual orientation.

        http://www.nexusmagazine.com/articles/CellularMemories.html [nexusmagazine.com]

        Whether it's true or not or just self selection bias I don't know. But I won't be surprised if the rest of our organs actually had some influence over what we'd like to put in our stomachs or other "gut feel stuff" ;).

        Plus those stem cells do roam about. After a
  • by cvd6262 (180823) on Thursday January 24, 2008 @01:51PM (#22169856)
    If CMV was really the cause of this strange, but fortunate, occurence, that's a tough one.

    CMV is no laughing matter. It's one of the opportunistic diseases that immuno-deficit people have to worry about. It can lead to blindness and a slew of other complications.

    The best we can hope for (if CMV is to thank for this effect) is that they can isolate the mechanism and replicate it. You wouldn't want to use CMV in this way.
    • by ivan256 (17499)
      I've actually heard of cases of this in the past, where the only reason the doctors noticed was because the recipient had gained the donor's peanut allergy. Perhaps that means it's not related to the CMV, but merely that the liver does more than we think...
  • by Phoenix666 (184391) on Thursday January 24, 2008 @01:51PM (#22169862)
    The implications for immunology and organ transplants are amazing, but it goes even further than that. If you can induce stem cells to penetrate a patient's bone marrow, then you open the door to all kinds of innovations.

    Imagine if they could take a sample of your DNA, correct inherited defects, and then re-implant you with stem cells carrying the corrected sequence. It would mean hope for victims of all kinds of diseases like Tay-Sachs or Kreuzfeld-Jacob.

    At the very least, the promise of being able to transfer immunological memory on the marrow level potentially means that all we have to do is find the one person whose immune system wipes out HIV, say, and we can all receive that same immunity.
    • Imagine if they could take a sample of your DNA, correct inherited defects, and then re-implant you with stem cells carrying the corrected sequence.

      We effectively already do this. They're called bone marrow transplants [wikipedia.org], and it's been used to treat a number of blood-based or auto-immune diseases for years.

      The risk of this procedure aside, one problem is that bone marrow transplants aren't perfect. Take leukemia or sickle cell anemia for instance. Unless every single hemopoietic stem cell is eradicate

    • Imagine if they could take a sample of your DNA, correct inherited defects, and then re-implant you with stem cells carrying the corrected sequence. It would mean hope for victims of all kinds of diseases like Tay-Sachs or Kreuzfeld-Jacob.

      All nice, but can you imagine what it would do for sports? This would be the ultimate doping.
    • by Ogive17 (691899)
      But then we'd lose all immunitizations the donor didn't have. Unless the plan was to keep switching immune systems every time a new disease was contracted....
  • 2 questions (Score:5, Interesting)

    by Stooshie (993666) on Thursday January 24, 2008 @01:52PM (#22169878) Journal

    As someone who has received a renal Tx and who also has a degree in Anat.,Phys.&Biochem. I have 2 questions.

    1. If her immune system has been replaced by her donors, won't her other organs/tissues (her own) be rejected by her new (her donor's) immune system?
    2. They gave her a liver from someone with a different blood type?!? I know other markers as well as blood type are taken into account (and in hepatic Tx urgency is another factor), but I thought a blood type match was the minimum requirement.
    • Re: (Score:3, Informative)

      by Henry V .009 (518000)
      If the blood type were AB to begin with, it could probably handle a liver from A, B or O.
      • Re:2 questions (Score:4, Informative)

        by Stooshie (993666) on Thursday January 24, 2008 @02:42PM (#22170740) Journal

        True to a certain extent. AB could probably handle O, but AB couldn't handle A or B (just the same as A couldn't handle B or vice versa). Having the A markers yourself, as an AB, doesn't neutralise the problems with the B vs A clashwith your B markers and their A markers).

        Certainly, when reciving blood, if she was AB positive, she can be a universal recipient. But that would be for an emergency blood transfusion. In an organ transplant situation it would be too risky.

        Just as a side note. The problems with different blood types in blood transfusions is less to do with rejection by the immune system and more to do with the blood cells co-aggulating. With a transplant the problem is more to do with rejection by the immune system.

    • If her immune system has been replaced by her donors, won't her other organs/tissues (her own) be rejected by her new (her donor's) immune system?

      Yes, but GVHD is not as bad as the combination of host versus transplant graft plus immune suppression. There is some talk of doing BMTs with other solid organ transplants to do exactly what this girl did spontaneously. Also, in the case of GVHD, the immune system is attacking OEM parts so they are healthier to start with than transplanted tissue.

      They gave her a liver from someone with a different blood type?!? I know other markers as well as blood type are taken into account (and in hepatic Tx urgency is another factor), but I thought a blood type match was the minimum requirement

      Not if you are going to die tomorrow. Once we get the liver equivalent of dialysis, this will change, but until then the threat of death from fulminant liver fai

    • Re:2 questions (Score:5, Informative)

      by Grym (725290) * on Thursday January 24, 2008 @02:50PM (#22170882)

      If her immune system has been replaced by her donors, won't her other organs/tissues (her own) be rejected by her new (her donor's) immune system?

      A better article [yourguide.com.au] on this case described her original blood group to be Type O negative(-) with her new blood group being Type O positive(+).

      In this special instance, there would be no reaction. Simply stated, anti-bodies can only be generated for antigens. Thus, you cannot have a humeral immune response based upon a lack of an antigen. This, incidentally, is the same reason why a type AB positive(+) person can receive blood transfusions from any blood group.

      They gave her a liver from someone with a different blood type?!? I know other markers as well as blood type are taken into account (and in hepatic Tx urgency is another factor), but I thought a blood type match was the minimum requirement.

      This is a good point. I can only guess that because the recipient's blood type was rare (approximately 9% of the population in Australia, according to wikipedia) and that the donors blood type was close (and perhaps their major histocompatibility was good too), other factors like urgency might have taken precedence over the ideal hope of a "perfect match."

      -Grym

    • Re: (Score:2, Informative)

      by rnws (554280)
      From what I can tell of from extracts from their paper the donor was the same blood type (O) with a different rhesus group.

      A person with group O can receive blood only from another group O person (but can donate to almost everyone else). RhD negative people who don't have anti-RhD antibodies can receive one transfusion of RhD positive blood then become sensitised to the RhD antigen.
      On the flipside, RhD positive people don't react to RhD negative blood.

      It's important to realise that the ABO and RhD+/
    • Re:2 questions (Score:5, Informative)

      by Anonymous Coward on Thursday January 24, 2008 @03:57PM (#22171938)
      Nope, a blood-type match is not required. I was a live liver donor two years ago,
      my blood type is O+, the recipient is A+.
  • by MouseR (3264)
    ... liver costs will skyrocket.
  • and will be issuing an embarrassing retraction here in a few days :)
  • by djlemma (1053860)
    ..to be able to transplant a new immune system into a patient with, say, some immune deficiency virus.. and potentially be able to add years to their life. Maybe you wouldn't need to bother with the anti-rejection drugs since the immune system of the patient would already be suppressed by the virus. I know it probably can't work that way, but I imagine that any major breakthroughs in the study of the human immune system will have relevance in AIDS/HIV research.
    • by peragrin (659227)
      damn that is a good thought, and I was wondering the same thing. Maybe AIDS/HIV patients could get a bone marrow transplant that would reintialize their immune system curing them of it.

      We just might be 5 years away from at least a partial cure.
    • A better question would be how exactly is this even happening? for the recipient to have taken on the immune system/blood type of the donpr there would need to be some way for these cells to develop in the first place. in other words, stem cells that can differentiate into such a complex system. knowing what caused it and how we can suplicate the effect if it did indeed occur in this manner has unimaginable potential for treating disease.
  • Wow, that's awesome. The first thing I thought of was, "wow, that was a lot of rep to farm to switch from scryer to aldor."

    I'm a sad sad man.
  • a lab error?
  • Accidents (Score:3, Insightful)

    by dj245 (732906) on Thursday January 24, 2008 @02:02PM (#22170052) Homepage
    It often takes accidents or other strange happenstances to spur innovation and invention. See Penicillin or any other number of other examples.
  • If they can reproduce this situation it'll be huge.

    If in fact they do reproduce it, do you think the doctors/researchers will get some sort of Nobel Prize?

  • the girl's immune system had almost totally been replaced by that of the donor, meaning she no longer had to take anti-rejection drugs.

    But what about all the rest of her body that was still running on the old immune system?

    • by gstoddart (321705)

      But what about all the rest of her body that was still running on the old immune system?

      The vendor will tell her she's running in an un-supported configuration.

      She'll have to either upgrade the rest of her body to Immune System 2.0, or revert to a saved image using Immune System 1.0. Unfortunately, they can't be responsible for any data loss from going back to the older version.

      It said right in the release notes that Immune System 2.0 wasn't compatible with Immune System 1.0, and they don't have any guidan

  • What would be really neat is if in 150 years, we could use this trick to make everyone's blood O-negative.

    Odds are we'll find a way to create effective blood substitutes well before then, but it would take some complexity out of the whole blood donor - donator process.
    • Re: (Score:3, Insightful)

      by KublaiKhan (522918)
      I'd not take that therapy, m'self--I've got AB+, so you can throw pretty much anything into me and I'll take it. Also, it's not just the blood type of the red cells that matters--the plasma has a type, as well, and it turns out that AB+ plasma can be given to anyone without any trouble.

      In addition, there are other possible consequences--some blood types, for instance, survive Bubonic Plague a lot more than other blood types, due to the similarity of surface proteins between certain kinds of blood cells
  • by spoonboy42 (146048) on Thursday January 24, 2008 @02:13PM (#22170246)

    This story actually coincides with an interesting story [npr.org] that ran on NPR yesterday about several experimental new transplant techniques that might help future transplant patients avoid having to take anti-rejection drugs, as well.

    In particular, the article tells the story of one 28-year-old woman who received a kidney transplant from her mother, who was only a partial match. Prior to the kidney transplant, she also received a partial bone marrow transplant from her mother. The bone marrow transplant essentially caused the patient's immune system to become a "blend" of her own and her mother's, producing T-cells that would attack bacterial and viral antigens just like normal, but leave the transplanted kidney alone.

    The results are pretty impressive. The patient originally had to take anti-rejection drugs after her first kidney transplant at age 13, and they caused a host of miserable side effects. After her more recent transplant, however, she's been off the drugs for five years and even ran 2 marathons last year (how's that for healthy?).

    Unfortunately, the new technique only works for organs that you intentionally plan on transplanting ahead of time, since the bone marrow has to be transplanted first in a separate surgery. That means that organ donors who die and donate hearts, livers, etc. aren't really an option. But for a transplant from a living donor, this is a very promising new technique (some of the researchers even think that it could eventually make transplants from animals possible).

    • Transplants from animals are already possible (apart from using human animals of course). Eg. pig heart valves, pig skin...
    • The Washington Post is also covering [washingtonpost.com] the new transplant technique, with a different human interest story attached.
    • Unfortunately, the new technique only works for organs that you intentionally plan on transplanting ahead of time, since the bone marrow has to be transplanted first in a separate surgery.

      Is doing them at the same time and using immuno-suppressant drugs until the new marrow kicks in too dangerous, or won't work for some reason? I don't think the donor would mind the painful and dangerous marrow donation process, since if they're donating other organs, they're probably done with the marrow, too.

  • "They saved Hitler's liver!"
  • by WillAffleckUW (858324) on Thursday January 24, 2008 @02:19PM (#22170358) Homepage Journal
    In Medical Genetics, we are very aware that the mother can frequently have immunities from all the embryonic stem cells from all her children, as well as her mother's children, and that later children have such stem cells and immunities from all their siblings - including from many of the non-viable pregnancies (not as much the ones that don't survive a few weeks, but stillborn children). Twins - fraternal, as identical have same germ line - share the cells of their siblings. Some twins are reabsorbed into the other twin, as well, resulting in a surviving child with both genetic structures, one predominant but the other continuing to "live" inside the body in survivor cells.

    The great thing about Pluripotent Stem Cells is that we may be able to do similar things by altering your own tissue into an embryonic cell, fixing the genetic deficit, and reinjecting the functional cells into your own body, where they can have a functioning immune system that is totally compatible with your own body and not be rejected.

    Science Rules!
  • Is it normal to transplant livers across blood types? This sounds like a nearly missed case of malpractice.
    • by NIckGorton (974753) on Thursday January 24, 2008 @02:54PM (#22170950)

      Is it normal to transplant livers across blood types?
      You can accept an Rh mismatch for a liver transplantation. And if you are going to die tomorrow, death from rejection in 5 years is a better deal.

      This sounds like a nearly missed case of malpractice.
      No. First of all this was not in the US. It is a uniquely American thing to assume that unless 1) All care is 100% perfect and 2) The outcome is 100% perfect, that you should sue your physician for malpractice.

      Despite the best care, sometimes bad things happen and people die. And sometimes the best care isn't possible, and you do the best you can as the doctors did in this case. The ideal is a perfect blood type and HLA match, however failing to act because you don't have a perfect match would have resulted in this child's death. Perfect in this case is the enemy of good.

      Unfortunately this sort of attitude creates no end to trouble and causes both inappropriately aggressive therapeutics and diagnostics in the US as opposed to elsewhere. There is a saying amongst OB/Gyns - you don't get sued for the C-Section that you do, you get sued for the C-Section you don't do. So surprise.... the US has a higher section rate for women. Similarly, in the US your child with belly pain is much more likely to get a CT scan to rule out appendicitis. Doing the CT doesn't get you sued, but failing to do it eventually will (because there is always going to be that very small number of kids with an appy that presented very atypically.) However, if you do 500 Abdominal CTs in kids less than 15, you will ultimately cause one excess cancer death in that group. But you won't get sued when the kid dies of renal cell cancer in his 40's. So kids with a very low risk of appendicitis instead of being observed (maybe even at home with responsible parents) will more often in the US get a trip to the donut and the resulting dose of radiation to their more vulnerable bodies.

      While it might seem that holding physicians to unreasonable expectations is beneficial, in the long run you will get worse care due to the practice of defensive medicine.
  • Chimeras are indviduals containing cells from two genomes. Mother-offspring chimeras maybe as high as 30%. Less common are sibling chimeras, via twin wombs or mother. And still more rare are father-offspring chimeras via organalles carried by the sperm and surviving fertilization.

    Usually these chimeras are highly assymetric with the alien cells out-numbered by originals by a thousand to one or so. True symmetric chimeras are rare, perhaps due to absorbed twins in the womb.

    This has created some pro
  • ... i wouldnt mind at all changing my immune system to something a little bit more sane.
  • In Soviet Russia, livers reject you!

    (I can't believe this actually almost makes sense)
  • It was conclusively demonstrated years ago that any old liver will do as long as it's paired with fava beans and a fine chianti.

Saliva causes cancer, but only if swallowed in small amounts over a long period of time. -- George Carlin

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