[Research Articles] Transitional B cell cytokines predict renal allograft outcomes
Early immunological biomarkers that predict rejection and chronic allograft loss are needed to inform preemptive therapy and improve long-term outcomes. Here, we prospectively examined the ratio of interleukin-10 (IL-10) to tumor necrosis factor–α (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 (n = 162) and Internal Validation (n = 82) 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 (n = 95) 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. To concl...
Source: Science Translational Medicine - Category: Biomedical Science Authors: Cherukuri, A., Salama, A. D., Mehta, R., Mohib, K., Zheng, L., Magee, C., Harber, M., Stauss, H., Baker, R. J., Tevar, A., Landsittel, D., Lakkis, F. G., Hariharan, S., Rothstein, D. M. Tags: Research Articles Source Type: research
More News: Allergy & Immunology | Biomedical Science | Bone Graft | Science | Training | Transplants | Universities & Medical Training