Kidney Transplant Rejection: American journal of Nephrology & Therapeutics (AJNT): ISSN 2643-7007
A kidney transplant can greatly improve the quality of life for people with kidney failure. But about 20% of donated
kidneys are attacked and destroyed by the recipient’s immune system. Transplant
rejection can happen despite daily treatments that suppress the immune system.
To help prevent rejection, doctors try to ensure that the recipient and
donor are a good genetic match. This includes measuring a group of proteins
found on the body’s cells called human leukocyte antigens (HLAs). HLAs help the
immune system tell which cells belong to the body and which might belong to
foreign invaders, such as bacteria.
The more HLAs that match between a kidney
donor and recipient, the more likely a transplant is to be successful. But even
a kidney perfectly matched by HLAs can be rejected. This has led scientists to
look for other proteins that might drive rejection.
Gene
deletions might play a role in transplant rejection. Common gene deletions
often have no obvious effects. But if a person with a deleted portion of a gene
received a kidney from someone with at least one intact copy of that gene, the
recipient’s immune system might see the protein produced by that gene as
foreign.
To test this idea, the researchers
measured the frequency of 50 known gene deletions in kidney donors and
recipients from around the world. They next looked to see if deletions in any
of the genes altered the risk of rejection.
The researchers first scanned for the 50
common deletions in DNA samples taken from 705 kidney transplant recipients. That
people with a deletion near a gene called LIMS1 had more than an 80%
higher risk of rejection than people with at least one intact copy of the gene.
More than 2,000 donor-recipient pairs. Found those people with the deletion near LIMS1 who received a kidney from a donor with at least one intact gene had a 58% higher risk of
rejection than people without this genetic mismatch.
Tested blood sera from 300 transplant
recipients. Antibodies targeting LIMS1 in all the
recipients with the gene deletion who’d experienced transplant rejection. These
antibodies weren’t found in the other recipients.
The LIMS1 deletion is absent
in people of East Asian ancestry but common in people of European and African
descent. The researchers estimated that a genetic mismatch in LIMS1 could
occur in up to 15% of transplants from unrelated donors in these groups.
“LIMS1 mismatches could be
avoided by pre-transplant genetic screening,” “But first we need to validate
our findings in larger studies.”
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