✕
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
Source: http://dx.doi.org/10.1126/scitranslmed.abe4929
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
Source: http://dx.doi.org/10.1126/scitranslmed.abe4929
1 / 1
Like
Comment
Share
