CD59 transgenics and xenotransplantation

The shortage of suitable donor organs for transplant surgery has led to the proposal that animal organs be used instead. A major problem with this is that of hyperacute rejection, whereby discordant xenografts come under attack within minutes, and are destroyed by complement that has been activated by naturally occurring antibodies in the host that recognize carbohydrate epitopes in the xenograft. A major strategy now being researched to overcome this is the production of transgenic animals (mainly pigs) that carry the genes for human complement control proteins, including CD59. These human proteins are expressed in a wide range of tissues in the transgenic animals, sometimes at very high levels, and have been shown to confer increased protection upon endothelial and other cell types against human complement. Although these results seem very promising, a major drawback to the use of xenotransplantation is the possibility that xenografts may harbor viruses or other microbes that could be extremely harmful to a human host, and this is currently the main objection to proceeding with clinical trials.

See also: CD antigens; CD2; Complement, membrane attack pathway; Decay-accelerating factor (CD55); Xenotransplantation.

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