Organ/Tissue Transplantation: The challenge of genetic diversity

Commentary

By Erin McMyne

December 6, 2005

Even though our scientific technology has brought us a long way, organ transplantation is one procedure that still provides us with many challenges. Not only is there a lack in organ donors, but matching a donor and recipient is like finding the right puzzle piece to fit into a jigsaw puzzle that is hundreds of thousands of pieces thanks to our genetic diversity.

Currently about 90,000 people are on the national waiting list to receive an organ. Looking at this past year from January to August, of those 90,000 or so people, only a mere 18,996 people received a donated organ.

These statistics are reported by the Organ Procurement and Transplantation Network (OPTN). The OPTN is a private, non-profit organization that was established by Congress in 1984 to help organize the many individuals who need a transplant, coordinate the matching process through medical professionals and to promoting increase in the number of organ donors.

When an organ becomes available, a computerized system is used to generate a list of possible recipients based on several factors; time the patient has been on the waiting list, geographic distance between the donor and recipient, degree of necessity and the most crucial: blood type and size of organ.

Because we as a population have such a diverse pool of proteins, matching a donor and recipient is the biggest challenge. Different individuals have different markers called major histocompatibility complexes which are present on all cells. These MHC's bind to specific protein fragments called peptides which may be from within the individual, from bacteria or in this case, foreign tissue from a donated organ. This peptide/MHC complex is recognized by lymphocytes (other cells of the immune system) and an immune response is generated. Such a mechanism evolved so that bacteria and other pathogens could be recognized and destroyed in order to protect an individual from infection.

This defensive immune response is also what leads to rejection of the donated organ in a recipient. Such rejection usually occurs within seven to fourteen days but the more closely related the donor and recipient, the better chance that they share more of the same MHC's and therefore more of the same peptides (antigens).

There are four different graft situations that vary based on the relatedness of the donor and recipient.

An auto-graft involves tissue on one individual being used on a different part of his/her own body. A common form of this is skin-grafting when someone has suffered severe burns and skin from an undamaged area of their body is used to replace the damaged area. In this case it's a perfect match because the graft is from the same individual so there should be no rejection.

When two genetically identical people, like identical twins make up the donor and recipient it's called an isograft; "iso" meaning equal or uniform because they share all of the same MHC's.

An allograft, on the other hand, involves two genetically different individuals within the same species. An allograft is the most common situation. In this case the matching process will involve comparing the population of different MHC's present in both individuals to identify how similar they are. The more alike, the less severe of an immune response could be generated.

A xenograft, or a tissue/organ from an entirely different species, is a new possibility that has become the focus of a lot of research and it holds promise for those who will be on the OPTN recipient waiting list in the future.

In general the immune response mediated by the T-cells causes other immune cells to come and destroy the kidney tissue because the immune system is telling the recipient's body that it is foreign or bad and needs to be gotten rid of. Cells like macrophages essentially digest and degrade the kidney tissue and other immune mechanisms activated include lysis (bursting) of the kidney cells that also destroys them. The immune system will also "remember" this antigenic tissue so that if a second transplant from the same individual occurs, a much more rapid immune response is generated.

Although rare, it is also possible for the donor organ to reject the recipient. This usually only occurs when the donated organ contains it's immune cells that can activate a response. This is common in a bone marrow transplant because that is the site of synthesis of certain immune cells and so bone marrow transplants are not common.

As you can see, unless you are lucky enough to be an identical twin, it is not easy to find another person who will have the same MHC's as you. Usually our defense against infection is beneficial but genetic diversity causes our immune system to act up at the inopportune time during organ/tissue transplantation. Until we can find a way to combat this challenge, matching a donor and recipient will continue to be a process involving extreme, detrimental process.

Copyright © 2005 The New Hampshire

This article posted January 1, 2006.