Genetic testing

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Tissue typing for transplantation

In the past, it was difficult to tell exactly whether an organ or tissue, such as a kidney, lung or bone marrow, was an exact match for the transplant between a donor and recipient. If it was not, a serious rejection reaction could sometimes occur between the recipient patient and the transplanted organ.

Basic laboratory testing for tissue transplantation involves mixing the white blood cells (leukocytes) from the donor (or the donor tissue) and the recipient together and observing whether an immune response occurs. Proliferation of a specific population of leukocytes signals the onset of an immune response and the likely rejection of the tissue by the recipient’s body. Although this technique is still commonly used, increasingly analysis of the DNA in both the donor and the recipient (tissue typing) is used to diminish the likelihood of rejection in the case of tissue transplantation. In bone marrow transplants, DNA testing is done to determine whether the leukocytes and their precursors repopulating a recipient’s bone marrow are their own or those of the donor.

A very specific set of genes is examined when DNA testing is used for tissue typing. On chromosome 6 resides a large set of genes in the so called “Major Histocompability Complex,” or MHC. These genes are very polymorphic (different) between individuals, and they code for the production of specific glycoprotein antigens located on the surface of many cells called the “human leukocyte antigens” or HLA. It is these antigens that allow our immune system to “recognise” our own organs and tissues from those of another individual. These antigens have the ability to provoke an immune system response that results in organ or tissue rejection if the tissue looks foreign. In tissue typing, the genes for a number of different HLA molecules are carefully compared between donor and recipient to ensure that they are as similar as possible to minimise the chance of a rejection.

The exact techniques used to test DNA for tissue typing are similar to those mentioned in the sections above. DNA is extracted from donor and recipient cells, then manipulated in such a way as to amplify specific regions or fragments on a chromosome and within the HLA genes. The amplified fragments are subjected to further analysis that allows for comparison of the polymorphisms in the HLA between the donor and the recipient. This careful analysis of genetic material results in fewer rejection reactions and a greater chance for a successful transplant.

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