Question

11. Alloantibodies specific for HLA class I molecules can mediate hyperacute rejection of kidney transplants. Explain under what conditions an individual would possess preexisting antibodies against HLA class I polymorphisms

Answer 1

Humans have three main MHC [ Major Histocompatibility Complex ] class I genes--- HLA-A, HLA-B and HLA-C. The proteins produced from these genes are present on the surface of all nucleated cells as transmembrane glycoproteins.

Alloantibodies is an antibody which is produced when an alloantigen is introduced into the body which is lacking that antibody.

Alloantigen is not present in all persons. It is a genetically determined antigen , just like blood groups, and is capable of inducing the production of alloantibody by individuals who lack it.

Pregnancy and blood transfusions can lead to the development of HLA specific alloantigens. Due to the extensive polymorphism of the HLA molecule, the specificity of the alloantigens is highly developed. Preformed alloantibodies that lead to hyperacute rejection of kidney transplants , have a direct effect on endothelial cells and cause severe endothelial damage, vascular thrombosis or graft rejection.

It is accepted that allograft rejection is the result of the recepient's alloimmune response to non-self HLA antigens expressed by donor tissues. Antibodies may cause tissue injury by themselves or in collaboration with immunocompetent cells.

With advanced technology, crossmatch tests are performed before transplantation and recipients with preformed anti-donor antibodies can be identified and chances of organ rejection can be minimised.

Mostly, pre-existing alloantibodies develop in response to pregnancy and blood transfusion. During pregnancy, the presence of alloantigens in the developing fetus might trigger the formation of alloantibodies in the mother.

Likewise, blood transfusions from a person might result in the introduction of alloantigens into the recepient, inducing the production of alloantigens.

In such cases , screening of the donor and recepients blood is necessary for compatibility and to reduce the risk of graft rejection.