Natural health ‘Missing self’ contributes to organ rejection after transplantation

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Immune cells called natural killer cells contribute to organ rejection after transplantation because they miss “self” proteins on donor cells, according to a study appearing in an upcoming issue of JASN. This process can be better understood by clinicians to prevent and treat rejection.

Transplanted organs are recognized by the immune system of the recipient as foreign or non-self, which leads to rejection of the organs. The treatment or prevention of rejection is done with drugs that suppress the immune systems, mostly targeting T immune cell. However, rejection can still occur despite such therapy. This is because the recipient’s immune system may recognize transplanted organs as foreign or non-self, which leads to rejection.

Natural killing cells play an important part in the immune system. They recognize and kill harmful cells, such as tumor cells. Sometimes, these harmful cells try to escape immune detection by decreasing MHC protein levels, proteins that are expressed on cells that allow T cell to recognize, bind to, and tolerate themselves. The T cells are unable to see the harmful cells through this mechanism, and so natural killer cells cannot. Natural killer cells are able to detect MHC proteins in the cells and kill them by using their KIR receptors. This is a crucial defense mechanism.

In transplantation, donor cells in an organ do not escape immune detection by decreasing MHC levels, but they express different MHC proteins to the recipient. The recipient’s natural killer cells become active because they have not detected the donor cells’ MHC and are therefore unable to detect them.

“This is exactly what we found in our study of 924 kidney transplantations: that the ‘missing self’ predicted by genetic analyses of the MHC molecules of donors and recipients, and the genetically determined KIR repertoire of the recipients, is predictive of rejection in kidney transplant biopsies,” said senior author Maarten Naesens, MD, Ph.D., of KU Leuven, in Belgium. Our study shows that genotyping donors and recipients for MHC, as is routinely done in clinical practice, and also for KIR will allow us to determine the presence or absence’missing self’ and improve the risk assessment for kidney transplant rejection.

“Furthermore, our findings demonstrate the importance of these natural killer cells after transplantation and suggest new ways to prevent or treat kidney transplant rejection,” added lead author Jasper Callemeyn, MD, also of KU Leuven.

More information:
“Missing self induced microvascular rejection of kidney allografts: a population-based study,” JASN, DOI: 10.1681/ASN. 2020111558

‘Missing self’ contributes to organ rejection after transplantation (2021, July 22)
retrieved 23 July 2021

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