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Early Immunologic Biomarker Predicts Renal Allograft Outcomes

FRIDAY, March 12, 2021 -- The ratio of interleukin-10 (IL-10) to tumor necrosis factor-α (TNFα) produced by transitional-1 B cells (T1B) predicts renal allograft outcomes, according to a study published in the Feb. 24 issue of Science Translational Medicine.

Aravind Cherukuri, M.B.B.S., Ph.D., from the University of Pittsburgh, and colleagues prospectively examined the ratio of IL-10/TNFα produced by T1B three months after renal transplantation as a predictive biomarker for 162 patients in a training set and 82 in an internal validation set.

The researchers found that the T1B IL-10/TNFα ratio at three months after transplantation predicted clinical and subclinical rejection in the first year. Subsequent late rejection was also predicted by the biomarker, with a lead time averaging eight months. Sixty percent of biomarker high-risk patients had early rejection, 48 percent of which recurred later in the first posttransplant year. Seventy-four percent of high-risk patients without early rejection developed rejection later in the first year. Among low-risk patients, 5 and 5 percent had early and late rejection, respectively. In an external validation set (95 patients) and in key patient subgroups, the biomarker predicted rejection. Compared with low-risk patients, biomarker high-risk patients exhibited progressively worse renal function and decreased five-year graft survival. Anti-TNFα treatment of B cells in vitro augmented the IL-10/TNFα ratio, restored regulatory activity, and inhibited plasmablast differentiation.

"The balance between IL-10 and TNF seems to indicate your immune setpoint -- is your immune system going to be quiescent or is it going to be revved up and try to reject the transplant? We hope we can restore that balance with anti-TNF drugs," a coauthor said in a statement.

Several authors disclosed financial ties to the biopharmaceutical industry.

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