Creating humans for spare parts

Tissue matching for transplants

30/7/03. By Richard Twyman

Ensuring that organ donors and recipients have the same antigens on the surface of their cells.

Tissue matching refers to the matching of donor and recipient tissue types in an organ transplant or tissue graft so that the likelihood of rejection is reduced. The tissue type of an individual depends on certain molecules, called human leukocyte antigens (HLAs), which are displayed on the cell surface. There are three major HLAs, known as HLA-A, HLA-B and HLA-DR. The antigens are proteins encoded by genes in the major histocompatibility complex on chromosome 6.

There is extensive polymorphism among the HLA genes, which means many different variants of each antigen exist in the human population. There are over 50 known variants of HLA-A and over 100 known variants each of HLA-B and HLA-DR. Some variants are much more common than others. Furthermore, everyone has two copies of chromosome 6 and may therefore produce two different versions of each HLA. This is why finding an exact tissue match – a six-antigen match – between two completely unrelated individuals is very difficult.

Fortunately, since families share the same genes they also tend to produce the same HLAs and therefore have related tissue types. It is much easier to obtain matching tissues and organs from a family member than it is from a non-relative.

The chance of finding an exact tissue match within the family depends on whether the antigens are common or rare in the population as a whole, and how closely two family members are related. Children inherit one copy of chromosome 6 from each parent and therefore have a mixture of parental antigens. If the HLA genes from each parent were mixed randomly, there would be a very small chance (<1 per cent) that any two siblings would have the same tissue type.

However, the three HLA genes on each chromosome are clustered together, and they tend to be inherited as a block (a haplotype). The chances of siblings sharing the same tissue type are therefore one in four (see figure below).

Prior to a graft or transplant, doctors determine the tissue types of the donor and recipient by testing for particular HLAs in serum samples, or by looking directly at the DNA sequence in the major histocompatibility complex. A six-antigen match is not always necessary because rejection can be overcome through the use of immunosuppressive drugs. However, if the recipient has already been exposed to one or more of the donor's HLAs (as might occur due to a previous blood transfusion) there may be antibodies already present that would increase the chances of rejection. This is tested by cross-matching, which involves mixing some of the donor's blood cells with the recipient's serum. If the cross-matching test is negative, the transplant is likely to be successful.

Three major histocompatibility antigens are encoded on each copy of chromosome 6, but they are inherited as a group. In this example, the child has inherited the 'green' haplotype from his father and the red haplotype from his mother. The chances of another sibling inheriting the same genes are 1 in 4.

Image credit: Darren Hopes

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