Some of the kidney donors and recipients may have a type of genetic incompatibility that leads to organ rejection

The study found that kidney recipients with two copies of a deletion near a gene called LIMS1 had a significantly higher risk of rejection when the donor kidney had at least one full-sized version of the same gene. The risk of rejection was 63 percent higher among the donor-recipient pairs with this genomic collision, compared to those without this mismatch. "To put this into perspective, the risk of rejection from LIMS1 mismatch is roughly three times as high as the risk due to a single allele mismatch in the HLA

Kidney transplant recipients with two copies of the deletion who developed rejection had detectable levels of anti-LIMS1 antibodies in their blood -- further evidence that this genomic collision contributes to rejection. "The exact mechanism by which this deletion exerts its effects is unknown," says Kiryluk. "It's likely that it reduces the amount of LIMS1 protein produced, since we find that individuals with two copies of the deletion have lower levels of LIMS1 gene transcript in their kidneys. When these individuals are exposed to a high level of LIMS1 protein in a newly transplanted organ, their immune system is more likely to recognize the LIMS1 antigen as foreign, resulting in rejection."

Transplanted organs commonly experience a significant period of low oxygenation, which appears to compound the genomic collision. In cells that produce LIMS1, the researchers found that low oxygen levels increase LIMS1 production on the cell surface, which may increase the risk of an immune attack.

LIMS1 mismatches would be expected to occur in approximately 12 to 15 percent of transplants from unrelated donors among persons of European and African ancestry, but it would be very rare among persons of East Asian ancestry because the deletion is very rare in these populations.

"LIMS1 mismatches could be avoided by pre-transplant genetic screening," Kiryluk says. "But first we need to validate our findings in larger studies."

The findings may apply to other types of organ transplants since LIMS1 is also expressed in the lung, heart, and liver. Similarly, other genetic incompatibilities may also be contributing to rejection of these organs.

Journal of Nephrology and Urology is an Open Access peer-reviewed publication that discusses current research and advancements in diagnosis and management of kidney disorders as well as related epidemiology, pathophysiology and molecular genetics.

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Journal of Nephrology and Urology