Short YouTube video here: https://youtube.com/shorts/J1iaCxsaLzs?si=LKV0ybIGXkxLmyaw
Summary is she received a liver transplant and because of some details discussed in the video, she has her donors blood. Since her donor was male, does that mean his dna, and only his dna, is found in a sample of her blood?
Completely so? Probably not?
First simplify this - end result was that is in the same place as a successful bone marrow transplant individual.
The blood cells, including immune system cells, are all from the donor, but the rest of the body is still host and there will be cell free DNA fragments floating about. Some of those fragments will be of sex chromosomes and mitochondrial origin. So not “completely” … but all DNA from whole cells in her blood, just as in a bone marrow transplant. Testing using a swab from the inside of her cheek (buccal swab), spit, or most not liver tissue biopsy, mostly her original female DNA.
Got it in one.
I’ve heard of cases when a bone marrow recipient has two sets of DNA, one being from the donor. The technical term for this is chimera. This New York Times article (gift link) describes one case where the recipient’s semen only has the donor’s DNA.
In the clip that is the bit that was so unusual, that the liver transplant had inadvertently resulted in “partial chimerism”, to a degree that the donor blood system and the host blood system were fighting it out - until they let the donor one win.
Apparently partial chimerism after liver transplant is not so infrequent:
We characterized the blood chimerism in a large cohort of 249 LT patients and analyzed putative HSPCs in adult human livers. The overall incidence of chimerism was 6.43%, of which 11.11% was among short-term (1 day to 6 months) and 3.77% was among long-term (6 months to 8 years) LT patients.
The taking over the bone marrow part though and donor becoming The One not so much so. Early micro chimerism actual correlates with better outcomes.
I’ve been able to find the case referenced in the clip published in NEJM here:
https://www.nejm.org/doi/full/10.1056/NEJMoa0707255
In summary, this patient required urgent liver transplantation for non–A-to-G hepatitis, and hemolytic anemia subsequently developed as a result of host-versus-graft disease, suggesting mixed hematopoietic chimerism. Withdrawal of immunosuppressive therapy resulted in resolution of the hemolytic anemia and the development of full hematologic chimerism. The complete absence of graft-versus-host disease and normal liver function in a fully HLA-mismatched, sex-mismatched liver allograft show that mixed chimerism with full tolerance can occur naturally under specific circumstances.
Thanks for your clear and concise explanation. I was framing a response with the same information, but way more words.
So to clarify - is this because the liver (and bone marrow) generate blood cells? So someone with a different transplant - heart, lungs, kidney, skin, etc. - would not test as different DNA unless the biopsy was straight from that replacement organ? (Other than minor cell fragments circulating?) I seem to recall something about a blood test for paternity tests that involves - somehow - fetal tissue that has crossed the placenta into the mother’s blood stream?
Is someone with chimerism obvious in a DNA test (too many markers?) or is it something the doctor or forensic scientist has to be warned about to look for?
Yes. If you’re testing from blood samples. (Maybe a trace if you’re testing a sample from an invasive biopsy method that includes some blood.)
In children, haematopoiesis occurs in the marrow of the long bones such as the femur and tibia. In adults, it occurs mainly in the pelvis, cranium, vertebrae, and sternum…In some cases, the liver, thymus, and spleen may resume their haematopoietic function, if necessary. This is called extramedullary haematopoiesis. It may cause these organs to increase in size substantially. During fetal development, since bones and thus the bone marrow develop later, the liver functions as the main haematopoietic organ. Therefore, the liver is enlarged during development.
Right.
Generally bone marrow makes all or nearly all the blood cells.
Again it isn’t so uncommon for a transplanted donor liver to make some blood cells too at least for a while (microchimerism). Not so many though and not often for very long.
In this case stem cells flooded out of the donor liver and started to compete with the host cells for dominance in the marrow and attacking each other in the blood stream, breaking down red blood cells, resulting in anemia (hemolytic anemia). Until the team pull back on the immunosuppressives which let the donor cells win and take over the bone marrow.
It is possible that those stem cells could have settled in some other locations as well, and such is reported after bone marrow transplantations. The linked NYT article reports cases of those stem cells even taking over the testes but FWIW I am not finding it in medical case reports. Only this recent article stating that such is at most rare and may just “not occur.” So not sure what to make of the NYT article claims.
This feels like the worst case kind of host versus graft rejection effect. It’s literally one immune system against the other.
I was thinking exactly the same thing.
There have been other cases of people who, for any number of reasons, decided to stop taking antirejection drugs, and never rejected their transplanted organ. It’s believed that stem cells that weren’t washed out of the donor organ engrafted in the bone marrow, and the immune system no longer recognized this organ as foreign.
In those cases, why doesn’t the immune system start to recognise the original organs as foreign?
Because somehow in those cases “central tolerance” was achieved, which is a huge goal to try achieve in transplant medicine.
What that means in this context is that as the donor blood system engrafted it eliminated the immature T cells that were recognizing self as “other”.
How exactly this happens? I get confused. Something about donor cells migrating to the thymus and re-educating the T cells there?
Here’s what I can find trying to explain how chimerism promotes central tolerance. The article is about a method being developed to create chimerism, thereby central tolerance, thereby less immunosuppressive therapy, by intent.
https://www.pnas.org/doi/10.1073/pnas.2214989119
The stable persistence of recipient and donor leukocytes in the transplanted patient, referred to as “chimerism”, was considered the reason why in some cases it was even possible to stop immunosuppressive treatment without damaging the transplanted organ. Unfortunately, it quickly became evident that stable, persistent allogeneic chimerism was not easily achievable by design. Recently, a novel approach has been identified to help address this clinical gap in knowledge: Cotransplantation of a donor graft with a thymic organoid populated with donor precursor cells generates stable, long-term chimerism in the recipient. In humanized mice, the implantation of thymic organoids, populated with human donor inducible pluripotent stem cell (iPSC)-derived thymic epithelial cells (TECs) and the same donor CD34+ bone marrow precursors, induces tolerance to human leukocyte antigen (HLA)-matched donor tissues/organs. This technology will allow successful allotransplantation of cells/organs even between Major Histocompatibility Complex (MHC)-noncompatible individuals and allow getting rid of immunosuppressive treatments reducing recipient morbidity.