(HealthDay News) — 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 Science Translational Medicine.
Aravind Cherukuri, MBBS, PhD, from the University of Pittsburgh, and colleagues prospectively examined the ratio of IL-10/TNFα produced by T1B 3 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 3 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 8 months. Sixty percent of biomarker high-risk patients had early rejection, 48% 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% 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 5-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.
Cherukuri A, Salama AD, Mehta R, et al. Transitional B cell cytokines predict renal allograft outcomes. Sci Translational Med. 13(582). doi:10.1126/scitranslmed.abe4929