Biomarkers of renal inflammation and chronic transplant failure

In view of the importance of local immune and inflammatory processes, we have developed immunohistochemical methods to characterize and quantify myeloid subsets in human renal biopsies (pre-transplant, protocol- and rejection biopsies). We have been able to demonstrate that the composition of infiltrate has an impact on the long term function of transplanted organs. Moreover we found that during rejection, also plasmacytoid DC were a major component of the infiltrate. Plasmacytoid DC are the natural alpha-IFN producing cells and implicated in defense against viral infections. Since viral (re)-activation (CMV, BK) is a major complication in immunosuppressed individuals, we investigate the contribution of pDC in this process.

For balanced use of immunosuppressive agents, it is of critical importance to have biomarkers which allow a close monitoring of the allo-specific immunity as well as of the ongoing inflammatory and injury response. We have an ongoing project (together with the department of Immunohematology) to evaluate and monitor the indirect pathway of allo recognition. Moreover we are exploiting the urine as a source of biomarkers, both using a hypothesis driven strategy (KIM-1, NGAL, MBL) as well as using an unbiased strategy of metabolomics (in collaboration with the departments of CPM- Center for Proteomics and Metabolomics and department of Clinical Chemistry)

Immune monitoring is also an important part of the research unravelling the amplifying mechanisms of auto-antibody mediated diseases like systemic lupus erythematosus (SLE) and ANCA-associated vasculitis (AAV). We have developed methods to quantify neutrophil extracellular traps to monitor this potential autoantigenic load in patients with SLE and AAV, and make use of high-sensitivity flowcytometry technique to monitor immunological effects of novel strategies of immunotherapy in SLE and AAV patients.