Friday, 24 October 2008

How is transplant rejection classified?

Immunological rejection of transplanted organs is divided into three categories, based on how long it takes for the rejection to develop. In each case, the time frame reflects the underlying process.

In hyperacute rejection, the transplanted organ is attacked virtually immediately, so that it begins to fail within hours or even minutes. In some cases, the surgeon doing the transplant can even tell that the organ is being rejected before he closes up! It appears that acute rejection is mediated by preformed antibodies, especially those directed against any non-matching HLA molecules in the transplanted organ.

You may ask where these antibodies come from, since they are there before the organ is transplanted. There are several sources, including blood transfusions (platelets and white cells are a bountiful source of HLA molecules), pregnancy (fetal HLA molecules may enter the mother's circulation), or previous transplants. Whatever the source, these antibodies are directed against, and lodge in, the vessel wall of the transplanted organ. They then activate complement in massive amounts, which ultimately leads to both the direct and indirect destruction of tissue, including thrombosis of the organ's vessels.

Next up is acute rejection. This is largely due to a T-cell driven cell mediated immunity attack, due to HLA compatibility. Antibodies do play a secondary role too, however. Acute rejection typically occurs 10-30 days after transplantation, and is characterised by an infiltrate of lymphocytes and macrophages.

Chronic rejection occurs gradually, over months to years. It is unclear what causes chronic rejection, but it may simply be a less vigorous form of acute rejection, especially when much acute rejection these days is prevented by immunosuppressive therapy. In some cases, this immunosuppressive therapy may so limit the inflammatory response that effects are only seen after many months.

In the next post, we'll briefly mention the main ways that we try to prevent rejection.

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