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Bone marrow and blood group


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When a person undergoes a bone marrow transplantation, their own bone marrow is "destroyed" by radiotherapy, chemotherapy or a combination of the two.  Donor bone marrow, sometimes of a completely different blood group is then introduced into the circulation of the recipient, and the stem cells migrate to the marrow and start to clone.  as they clone and develop, so the developing cells (red, white and platelet) start to come out into the circulation (although not all at once - the red cells are usually, but not always first).  At the same time, the patient's own red cells are gradually removed from the circulation by a form of apoptosis, called eryptosis, by splenic macrophages.  Eventually, the donor's red cells will make up 100% of the circulating population (although the patient may require transfusion support for some time), and by the time this happens, if the donor's blood group differs from that of the recipient, the recipient's blood group will, effectively, have changed to that of the donor (at least, this is true for all antigens that are intrinsic to the red cell membrane - those that are adsorbed onto the red cell surface from the plasma, for example, Lewis, Chido/Rodgers, will stay the same as the recipient's original type).

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If you examine the chromosomes from, for example, the patient's cheek, the genes within these chromosomes will, indeed, be the patient's.

The patient's own bone marrow, however, will have been destroyed by chemotherapy, radiotherapy or both.  This has been replaced by bone marrow from the donor, which will be HLA compatible (so that it will not be destroyed by what little remains of the recipient's immune system, but which will be close enough to the recipient's HLA type so as not to cause devastating Graft-versus-Host Disease [GvHD]).  So, if cells are taken from the bone marrow of the recipient (once the transplant is shown to have been successful), the chromosomes will be those of the donor (or largely so, there may be a few residual cells derived from the recipient present), and the genes on them will be the donor's.  As a result, the antigens expressed on the red cell surface (or, at least, those antigens that are intrinsic to the red cell membrane) will be encoded by the donor's genes, rather than the recipient's genes and, of course, the cellular immune system (also derived from the donor bone marrow), will "see" these as "self", as so will not destroy these red cells.  This is why the HLA type of the donor and the recipient has to be so close, so that the donor-derived cellular immune system does not "see" the rest of the recipient's body (skin, gut, body organs, you name it) as "foreign", and destroys the recipient's body through GvHD.

In short, the recipient's body (skin, gut, body organs, etc) will have the recipient's own genes, but the bone marrow (from where the white cells, red cells and platelets derive) will have the donor's genes, and this could mean a change of blood group.  In fact, unless the donor is an identical twin, or the bone marrow is autologous, it is almost certain that there will be a change in blood group, if only within the minor blood group systems.

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1 hour ago, Malcolm Needs said:

If you examine the chromosomes from, for example, the patient's cheek, the genes within these chromosomes will, indeed, be the patient's. 

The patient's own bone marrow, however, will have been destroyed by chemotherapy, radiotherapy or both.  This has been replaced by bone marrow from the donor, which will be HLA compatible (so that it will not be destroyed by what little remains of the recipient's immune system, but which will be close enough to the recipient's HLA type so as not to cause devastating Graft-versus-Host Disease [GvHD]).  So, if cells are taken from the bone marrow of the recipient (once the transplant is shown to have been successful), the chromosomes will be those of the donor (or largely so, there may be a few residual cells derived from the recipient present), and the genes on them will be the donor's.  As a result, the antigens expressed on the red cell surface (or, at least, those antigens that are intrinsic to the red cell membrane) will be encoded by the donor's genes, rather than the recipient's genes and, of course, the cellular immune system (also derived from the donor bone marrow), will "see" these as "self", as so will not destroy these red cells.  This is why the HLA type of the donor and the recipient has to be so close, so that the donor-derived cellular immune system does not "see" the rest of the recipient's body (skin, gut, body organs, you name it) as "foreign", and destroys the recipient's body through GvHD.

In short, the recipient's body (skin, gut, body organs, etc) will have the recipient's own genes, but the bone marrow (from where the white cells, red cells and platelets derive) will have the donor's genes, and this could mean a change of blood group.  In fact, unless the donor is an identical twin, or the bone marrow is autologous, it is almost certain that there will be a change in blood group, if only within the minor blood group systems.

Thanks alot for this useful explanation   and excuse me for my questions

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My student asked about the original natural antibodies in the plasma -  I assume they're "wiped out" with patient's B cells in the chemo/radiation and the transplanted B cells in the donor's marrow makes the appropriate antibody(ies) for the patient's new blood type.  What about the tissue/organs that express ABO antigens though?  Please help Malcolm.

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Hmmmm!  This is actually quite a difficult concept, but I'll try.

Yes, as the patient's own B lymphocytes "die off", so the recipient's ABO antibodies (and any other antibodies they may have made) weaken and eventually become undetectable by normal serological techniques.  Once the bone marrow has "taken", it would be expected that the recipient's circulation would contain the expected ABO antibodies of the donor's type.  However, this is not necessarily the case, and it is not just down to immuno-suppresive drugs.

If, for example, the recipient was originally group A, and the donor was group O, one would expect to see anti-A and anti-B (and anti-A,B) in the recipient's plasma, but this is not what happens (particularly if the recipient was a Secretor).  The ABO antigens are, indeed, histoantigens (superb question and knowledge by your student by the way - I am very impressed), but, in addition, Type 1 ABO antigens (the ABO antigens that are found in the plasma) are produced outside of the bone marrow, and so both will continue to be produced for the rest of the recipient's natural life.  As a result, instead of seeing anti-A, anti-B and anti-A,B in the recipient's plasma, as might be expected, one tends only to see anti-B (and, on some occasions anti-A1 - but not either anti-A or anti-A,B).  There are several theories as to why this may be.

The two most commonly theorised reasons are because either anti-A (and anti-A,B) is actually produced, but is adsorbed out of the recipient's plasma by the A histoantigen and/or the A substance, or that anti-A is not produced in the first place, because the donor's immune system (or, as it now is, the recipient's immune system) has "learned" that the A antigen is now "self" (a sort of "accommodation"), and so the anti-A (and anti-A,B) is not produced in the first place.  Certainly, from experiments I did in the late 1980's, in such a situation, using polyclonal human-derived high-titre anti-A, it was possible to adsorb this anti-A onto apparently group O red cells derived from the recipient many, many months after the bone marrow had apparently "taken", and adsorb it back off; probably as a result of the plasma soluble Type 1 A substance being adsorbed onto the "donor" group O red cells in vivo in the recipient's circulation.

A much more recent paper on this subject is by Hult AK, Dykes JH, Storry JR, Olsson ML.  A and B antigen levels acquired by group O donor-derived erythrocytes following ABO-non-identical transfusion or minor AB)-incompatible haematopoietic stem cell transplantation.  Transfusion Medicine 2017; 27: 181-191.  Doi: 10.1111/tme.12411.  In this, they are gracious enough to refer to my paper, I am egocentric enough to record (as it was my first ever paper), but I should warn you that the Hult is not the easiest paper to read and understand (or it could be me being thick)!

I hope all that helps both you and your impressive student.  It sounds like he or she should go far in their chosen profession.

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