Project Details
Projekt
Chemokines of the CXCR3L family and their receptor in sclerodermatous chronic GVHD
Subject Area
Hematology, Oncology
Term
from 2015 to 2019
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 275338628
This project will test the hypothesis that dysregulated chemokine expression of the CXCR3 ligand family or their receptor plays a specific role in the development of severe chronic GVHD of the skin. Severe chronic GVHD is an iatrogenic complication after allogeneic stem cell transplantation. It is associated with increased mortality rates. Most patients with severe chronic GVHD have achieved complete remissions of their malignant diseases. Nevertheless, the substantial morbidity with an imminent disablement, occasionally culminating in complete helplessness of these patients remains an unsolved clinical problem. There are no convincing concepts to explain the pathophysiology of chronic sclerodermatous GVHD so far. Our proposal is based on a well characterized cohort of 424 patients with completely compiled clinical data and prospectively collected blood samples before transplantation and longitudinally weekly and second weekly for one year after. We will perform ex vivo analyses and correlate them with clinical outcome. Furthermore, all results will be verified on independent control cohorts.Examining serum and blood cells, we will test the hypothesis that protein expression levels of CXCR3 and its ligands is specifically dysregulated in sclerodermatous GVHD. Furthermore we will examine the recipients DNA for single nucleotide polymorphisms (SNPs) in all CXCR3 family members. The functional relevance of these mutations will be tested by correlation with RNA and protein expression levels and with the development of complications after allogeneic stem cell transplantation, in particular with chronic sclerodermatous GVHD.Based on our own preliminary results we expect a specific association of CXCR3 and its ligands with chronic sclerodermatous GVHD. The findings will serve as a rationale for targeted treatment strategies with specific CXCR3 inhibitors for severe chronic GVHD of the skin.
DFG Programme
Research Grants
