'Missing self' contributes to organ rejection after transplantation
Study identifies a major role for immune cells called natural killer
cells in organ rejection.

Date:
July 22, 2021
Source:
American Society of Nephrology
Summary:
After kidney transplantation, natural killer cells of the
recipient become active because they miss 'self' proteins on donor
cells. These cells contribute to organ rejection, in addition to
traditional modes of rejection involving T cells and antibodies.



FULL STORY ========================================================================== 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. A better understanding of this process may help clinicians prevent and treat
organ rejection.


========================================================================== Transplanted organs are recognized by the immune system of the recipient
as foreign or non-self, which leads to rejection of the organs. Rejection
is prevented or treated with drugs that suppress the immune system,
mostly targeting T immune cells; however, rejection can still occur
despite such treatment, not only because T cells may not be completely suppressed by the therapy, but also because of antibodies and "natural
killer cells" that target the donor tissue.

Natural killer cells play an important role in the human immune system,
as they are involved in recognizing and killing harmful cells such as
tumor cells.

These harmful cells sometimes attempt to escape immune detection by
decreasing MHC proteins, which are proteins expressed on cells that
allow T cells to bind to, recognize, and tolerate itself. This mechanism renders the harmful cells invisible to T cells, but not to natural killer cells. Through their KIR receptors, natural killer cells can detect the
absence of these MHC proteins and therefore kill the harmful cells. This constitutes a very important defense mechanism.

In transplantation, the donor cells in the transplanted organ are not
escaping immune detection by decreasing MHC expression, but these donor
cells express different MHC proteins than the recipient. The natural
killer cells of the recipient therefore miss the "self" MHC on these
donor cells and become active.

"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, PhD, of
KU Leuven, in Belgium. "Therefore, our study shows that genotyping the
donors and recipients not only for MHC (as is done in routine clinical practice), but also for KIR, will enable us to assess the presence or
absence of 'missing self,' and improve the risk assessment of 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.

Study co-authors include Aleksandar Senev, MD, PhD, Maarten Coemans, PhD, Evelyne Lerut, MD, PhD, Ben Sprangers, MD, PhD, Dirk Kuypers, MD, PhD,
Alice Koenig, MD, PhD, Olivier Thaunat, MD, PhD, and Marie-Paule Emonds,
MD, PhD.

Disclosures: This work was supported by a project grant from the Research Foundation Flanders.

========================================================================== Story Source: Materials provided by American_Society_of_Nephrology. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Jasper Callemeyn, Aleksandar Senev, Maarten Coemans, Evelyne
Lerut, Ben
Sprangers, Dirk Kuypers, Alice Koenig, Olivier Thaunat, Marie-Paule
Emonds, Maarten Naesens. Missing Self-Induced Microvascular
Rejection of Kidney Allografts: A Population-Based Study. Journal
of the American Society of Nephrology, 2021; ASN.2020111558 DOI:
10.1681/ASN.2020111558 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/07/210722171215.htm

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