The goal of my research is to identify renal transplant patients at risk for premature allograft loss to facilitate early interventions. To address this, our group focuses on early immunological and clinical predictors for poor clinical transplant outcomes.

We have discovered that human Breg activity is best determined by their ratio of IL-10/TNFa expression. Of all B cell subsets, the immature transitional B cells (TrBs) have the highest IL-10/TNFa ratio, suggesting that they enrich for Bregs. Their IL-10/TNF? ratio falls with late renal allograft rejection and predicts subsequent allograft decline. Based on our initial findings, we have initiated and completed a prospective study of B cell subsets and cytokines as a predictive biomarker for clinical and sub-clinical renal allograft rejection and subsequent clinical course. We have tested and validated a strong biomarker based on the T1B IL-10/TNFa ratio of the immature T1 transitional B cells in the peripheral blood and uncovered an immunological imbalance that can be potentially reversed by immunomodulatory agents. A multi-center RCT is being planned based on our biomarker findings.

We have shown that low-grade early post-transplant proteinuria, especially when it progresses through the first few years after transplantation is associated with poor clinical outcomes. Further, proteinuria risk stratifies renal transplant recipients with TCMR. Next, our work highlighted a clinical paradigm where evolution of a mature immune response as evidenced by the development of DSA and TCMR which is often sub-clinical leads to premature allograft loss when compounded by non-adherence (3 hits).