Pittsburgh Steelers Chair of Transplantation and Professor of Surgery, Medicine and Immunology at the University of Pittsburgh School of Medicine. Photo credit: Thomas E. Starzl Transplant Institute at the University of Pittsburgh
Researchers at the University of Pittsburgh Medical School have discovered a blood biomarker that predicts kidney transplant rejection around eight months lead time and could give doctors the ability to intervene and prevent permanent damage.
These results, published today in Science Translational Medicine, not only identify a warning sign that something is going wrong, but also suggest an existing drug that could be given to these patients to correct the course of their long-term recovery.
“We can’t tell a priori whether a patient has too much or too little immunosuppression – we don’t know until after rejection or infection has started,” said senior author David Rothstein, MD, of the Pittsburgh Steelers Chair in Transplantation and Professor of Surgery, Medicine, and Immunology at Pitt. “We wanted to find something that would tell us that this patient is at risk of being rejected later, so we can switch immunosuppressants ahead of time, before the immune system turns, before scarring and chronic damage occurs.”
About a third of patients lose their kidney transplant within 10 years, and at this point a new transplant is not easy. The patient’s immune system is already sensitized to the foreign organ and it is more difficult to find a match.
Rothstein and his colleagues at the Thomas E. Starzl Transplant Institute in Pitt analyzed blood samples from 244 patients who received kidney transplants at UPMC between 2013 and 2015, as well as from a further 95 kidney transplant patients treated at the Royal Free Hospital, London. and found a very predictive biomarker.
Drs. Rothstein and Cherukuri discuss the importance of a predictive biomarker for kidney transplantation and review their results. Photo credit: David Rothstein and Aravind Cherukuri
Of those patients who were found to be at high risk of rejection based on this new biomarker, 91% rejected the organ within the first year, compared with 10% in the low-risk group. And the high-risk group lost their transplanted kidneys significantly more often five years after surgery. The biomarker discovered by Rothstein and colleagues is a proxy for the function of regulatory B cells – a type of immune cell that tunes the immune response up or down – that have recently been involved in organ rejection and have proven difficult to measure. B cells can secrete both IL-10 and tumor necrosis factor (TNF). According to this new study, it is the ratio of these two molecules that best measures B-cell regulatory activity and predicts whether a patient is at high risk of rejection.
“As a functional biomarker, we give ourselves an idea of what goes wrong with these high-risk patients,” said Rothstein. “The balance between IL-10 and TNF seems to indicate your immune set-point – is your immune system dormant or is it revving up and trying to refuse the transplant? We hope we can restore that balance with anti-TNF drugs. “
Anti-TNF drugs have not been widely used in transplant patients, but they are a mainstay in the treatment of rheumatoid arthritis, inflammatory bowel disease, and other conditions characterized by inflammation. Therefore the side effect profile is known.
To minimize this risk, the idea is to only treat patients with anti-TNF drugs for a few months. This could be enough to reset the immune system and prevent rejection before it starts.
A human clinical trial is required, but to prove the principle, Rothstein and colleagues applied anti-TNF to B cells from high risk patients and saw not only changes in the biomarker but a host of other changes following a restored one Regulation indicate B cell activity.
An early blood marker can predict the future risk of kidney transplant failure
A. Cherukuri el al., “Transitional B-Cell Cytokines Predict Kidney Allograft Outcomes”, Science Translational Medicine (2021). stm.sciencemag.org/lookup/doi/… scitranslmed.abe4929 Provided by the University of Pittsburgh
Quote: The blood test for kidney rejection proposes a new method of treating patients after the transplant (2021, February 24), which will be released on February 24, 2021 at https://medicalxpress.com/news/2021-02-blood-kidney- post-transplant-patients. html
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