There are 4 blood types (A, B, AB, and O), each referred to by the letter of the inherited antigenpresent on the red blood cell surface. People with blood type A will have antibodies to the B antigen, whereas people with blood type B will have antibodies to the A antigen. People with blood type AB will have no preformed antibodies, and people with blood type O have no antigens on their red blood cell surface and thus have antibodies to both A and B antigens. Due to these preformed antibodies, organ transplantation from an ABO-incompatible donor does not work because of a complement mediated hyperacute rejection against the blood group antigen(s) present on the vascular endothelial cells of the donor organ.
Due to limited organ availability leading to a high mortality for young children, physicians have used their knowledge of immunology to work around this ABO issue. Newborns and infants have a relative immature immune system, with very low A or B antibody titers till 1 year of age. Furthermore, the complement system is not fully proficient in young infants. Due to these two key facts, successful heart and liver transplantations from ABO-incompatible donors have been performed in infants. These children did not experience hyperacute rejection and had the same outcome as related to survival and quality of graft when compared to ABO compatible recipients.
As the transplanted children became older (and developed a more mature immune system), they did NOT develop antibodies to the blood type antigen(s) expressed by the donor organ. The development of this “B-cell tolerance” is similar to mechanisms used in T-cell tolerance of clonal deletion and anergy. For children > 1 year and adults, more aggressive therapies to circumvent the B cell response have been tried which include: plasmapheresis, which removes all preformed antibody; splenectomy, which decreases new antibody formation, however, severely affects how people can fight off certain bacterial infection; and lastly, pharmacological B cell modulators, such as rituxamib (anti-CD20 monoclonal antibody) and mycophenolate mofetil (inhibits B cell proliferation). Though all of the above are marvelous techniques to stretch a scarce resource, the best solution would be more available organs. Please sign you organ donation cards!
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4 comments:
So this has been done, cool. Were there more complications, rejection episodes, in these children when compared to the blood matched children? Do you have the percentages for the two catagories of patients?
I looked at 4 case series, with 3-22 patients each. The case series with the most patients looked at complications between the ABO compatible and ABO incompatible group and was powered to look for difference in the development of vascular complications, rejection episodes, and patient/graft survival. 38% of patients in both groups had rejection episodes, the only significant difference was the time to develop the first bout of rejection. The ABO incompatible group developed rejection on averate of 144 days compared to 307 days (P value < 0.001). Both groups had similar survival outcomes.
Hmmm, I'm a little unclear on how the B-cell tolerance is acheived in this context. B-cells, when developing/ maturing in the bone marrow will undergo apoptosis if they bind too tightly to antigens in the marrow, but in the case of these transplantations, the mismatched ABO antigens are not in the marrow? Also, clearly, B-cell tolerance is not as important as T-cell tolerance because with T cell help, the B-cell cannot achieve class switch and produce high levels of IgG... so the question is why IS there T-cell tolerance in these children... I thought that the antigens exposed to developing T cells in the person are strictly endogenous to the person, therefore why isn't the ABO mismatch in the transplanted organ seen as foreign?
As we will soon see in class, the antibodies normally made against A and B blood groups antigens are IgM; and so they are T-independent. Thus the T cell tolerance issue is not involved in this special case. It is curious that these kids seem to become tolerant to these antigens. We do know that the IV route tends to be "tolerogenic" more than intramuscular or subcutaneous, though.
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