Transitional B cell cytokines predict renal allograft outcom
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Researchers have discovered a blood biomarker that predicts kidney transplant rejection with a lead time of about eight months, which could give doctors an opportunity to intervene and prevent permanent damage.

Researchers prospectively examined the ratio of IL-10 to TNFα produced by transitional-1 B cells (T1B) 3 months after transplantation as a predictive biomarker for clinical and subclinical renal allograft rejection and subsequent clinical course.

--In both Training and Internal Validation Sets, the T1B IL-10/TNFα ratio 3 months after transplantation predicted both clinical and subclinical rejection anytime in the first year.

--The biomarker also predicted subsequent late rejection with a lead time averaging 8 months.

--Among biomarker high-risk patients, 60% had early rejection, of which 48% recurred later in the first posttransplant year.

--Among high-risk patients without early rejection, 74% developed rejection later in the first year. In contrast, only 5% of low-risk patients had early and 5% late rejection.

--The biomarker also predicted rejection in an External Validation Set and in key patient subgroups, confirming generalizability.

--Biomarker high-risk patients exhibited progressively worse renal function and decreased 5-year graft survival compared to low-risk patients.

--Treatment of B cells with anti-TNFα in vitro augmented the IL-10/TNFα ratio, restored regulatory activity, and inhibited plasmablast differentiation.

In conclusion, the T1B IL-10/TNFα ratio was validated as a strong predictive biomarker of renal allograft outcomes and provides a rationale for preemptive therapeutic intervention with TNF blockade.

Science Translational Medicine