video: Drs. Rothstein and Cherukuri discuss the importance of a predictive biomarker in kidney transplantation and review their findings. This material relates to a paper that appeared in the Feb. 24, 2021, issue of Science Translational Medicine, published by AAAS. The paper, by A. Cherukuri at University of Pittsburgh in Pittsburgh, PA; and colleagues was titled, "Transitional B cell cytokines predict renal allograft outcomes." view more
Credit: David Rothstein and Aravind Cherukuri
Scientists have found that comparing the ratio of two immune molecules helped predict the likelihood of transplant rejection in 339 patients who received kidney transplants, the only curative treatment for late-stage kidney failure. Their results suggest that monitoring this ratio could help distinguish high-risk patients early on, before long-term organ rejection becomes inevitable, allowing clinicians to intervene accordingly with new treatments. Kidney transplants often grant immediate benefits to patients with end-stage kidney disease, but long-term outcomes are mixed, as 35% of transplant recipients lose their new kidney within 10 years. Researchers theorize this long-term rejection results from a slow, insidious buildup of damage from the immune system in the transplanted kidney, which often cannot be detected until it has become irreversible. Aravind Cherukuri and colleagues investigated whether there might be ways to identify high-risk patients during the initial months after transplant, when long-term damage may still be treatable. They studied kidney biopsies from 244 patients who received kidney transplants and focused their attention on IL-10 and TNFα, two immune molecules that are secreted by B cells. The analysis revealed that patients with a low ratio of IL-10 to TNFα three months after transplant had up to a 74% risk of later rejection within the first year, while patients with high ratios showed only a 5% chance of early or late rejection. The team observed similar patterns in a second group of 95 patients, observing that grafts in high-risk patients had poorer five-year survival rates compared with grafts in low-risk patients. Interestingly, Cherukuri et al. found that treating isolated B cells with antibodies against TNFα restored the IL-10/TNFα ratio to normal levels, suggesting that this strategy may help reduce long-term rejections if given early to high-risk patients.
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Journal
Science Translational Medicine