Project Details
Projekt
Transitional B cell cytokine ratio as a prognostic biomarker for clinical course in renal transplantation that guides therapeutic intervention
Applicant
Dr. Dominik Chittka
Subject Area
Nephrology
Immunology
Immunology
Term
from 2017 to 2018
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 394720292
Despite remarkable improvements in short-term outcomes in kidney transplantation, chronic rejection and subsequent allograft loss remain a major problem. Late allograft loss is increasingly attributed to cumulative effects of underlying subclinical immunological injury that occurs despite potent immunosuppression. Neither clinical parameters nor early surveillance biopsies can predict long-term outcomes accurately enough to individualize immunosuppressive therapy based on actual risk. Thus, predictive biomarkers are required to identify at-risk patients so that pre-emptive therapy can be initiated before damage occurs. While B cells produce antibodies that can contribute to allograft rejection, they can also profoundly influence immune cell responses through antigen presentation, co-stimulation, and cytokine secretion. Depending on their cytokine profile, B cells either exhibit pro- or anti-inflammatory (regulatory) activity. Such regulatory and inflammatory B cells may help establish an important immunological set-point, but their role in humans and especially in organ transplantation is still poorly understood. Promising preliminary data indicate that the ratio of IL-10:TNF-alpha expression in B cell subsets may act as a predictive biomarker for long-term clinical outcomes in kidney transplantation. If confirmed, this assay could serve as the basis for pre-emptive therapeutic strategies in high-risk patients, to reduce immune-mediated damage and improve long-term outcomes. Moreover, this biomarker may provide insight into innovative therapeutic strategies required to improve transplant survival.
DFG Programme
Research Fellowships
International Connection
USA
