Saturday, August 4, 2012

Findings reveal new difficulties for transplantations

There is a great need for more organ donors, because there are not enough replacements, such as heart, kidney or lung, to provide all patients with the organs they require. Because being an organ donor can save lives, in case yours can no longer be saved, getting registered as a donor is something everyone of us should do. However, availability is not the only issue in transplantation. Scientists have had to put in a lot of effort in order to get transplantations to work, because our bodies are not quite prone to accepting organs from others. Due to our increased knowledge, we have gotten transplantation procedures to work, but scientists from the University of California in Berkeley have discovered new difficulties.

One of the most important factors governing compatibility between a recipient and a donated organ is HLA. This molecule is present on the surface of every cell, and functions as a marker for the immune system to distinguish self from non-self. Basically, they present small pieces of protein that are constantly ground down inside the cell. To put it simply, this is done so the immune system can 'check' the internal contents, which could for example reveal a viral infection, by presenting parts of viral proteins. If this is the case, the immune system will destroy the infected cell.

HLA is necessary for antigen presenting, a process described in the paragraph above. Because it can trigger a deadly response from the immune system, it is not hard to imagine why HLA is involved with autoimmunity when something goes wrong: when immune cells do not recognize something as part of the 'self', they launch an attack. They do the same when encountering HLA molecules derived from cells present on a donor organ. Due to the variety in HLA genes, not everybody constructs the same HLA molecule, and this variety is important to take into account when matching an organ with a recipient: this is called HLA matching.
The basic concept of HLA and the immune system. An infected cell presents parts of proteins obtained due to infection, which is consequently recognized by a T cell, which is part of the immune system.
As said, there is variety between HLA's of individuals. The scientists set out to map all the differences we can find, because this would help with matching organs to recipients. However, they found that the genes responsible for creating a functional HLA molecule rapidly evolve. That means the structure of the genes change, and this has consequences for the corresponding structure of the HLA molecule. The scientists think there are currently over a million different variants, and trying to uncover all the possibilities will be a fruitless endeavour.

We can do a lot in order to make a body accept an organ. Normally, a patient receives immunosuppressants to shut the immune system down. This is especially necessary because exact HLA matching is virtually impossible, but also because there are other, more complicated factors involved with organ rejection. Exact HLA matching would be beneficial, but the present study reveals this is likely to be impossible. Of course, none of this will be necessary when we find a way to grow organs in the lab based on the patient's own cells, which would not be recognized as foreign. Until then, scientists and doctors will have to make ends meet and try to match HLA molecules the best they can, knowing that getting identical twins will not be possible.

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