Pathogenesis of ANCA vasculitis
Pathogenesis of large vessel vasculitis
Immuno-pathogenesis research, encompassing basic cell and molecular science, experimental medicine and clinical trials is a critical component of the Centre’s work and one we care keenly to expand.
In collaboration with immunology colleagues, patient-derived samples are used to study the effect of ANCA on:
- Neutrophils and monocyte behaviour focusing on intra-cellular signalling pathways
- Formation of neutrophil extracellular traps
- Role of danger-associated molecular patterns (DAMPS), such as calprotectin.
In parallel reproducible and accurate rodent models of ANCA vasculitis have been used to:
- Study the effect of ANCA on leucocyte-endothelial cell interactions
- Test a variety of potential therapeutic agents, including inhibition of SYK
- Study CD20+ B cell and Th17 lymphocyte subsets, lymphocyte survival factors (BLyS and APRIL) and effector cytokines (e.g. IL-17)
- Identify urinary MCP-1 as a biomarker of active renal vasculitis
With colleagues from across the Imperial Vascular Science Network the Centre we analyse patient-derived endothelial colony-forming cells (ECFC) and extracellular vesicles
- ECFC derived from peripheral blood exhibit an endothelial phenotype
- We are pioneering the study of endothelial colony-forming cell analysis in vasculitis
- Determining their potential role as true biomarkers, and a means to understand effects on endothelial cellular signalling and function
- On-going analysis is correlating levels of plasma extracellular vesicles with matched imaging data.
The new Centre for Vasculitis Research has already provided additional impetus and opportunity to develop cross-faculty collaborations, so strengthening and diversifying our research programme to areas including:
- Targeted drug delivery using engineered nanomedicines to enhance drug efficacy while minimising toxicity (with Natural Sciences)
- Clinical trials including BIOVAS in rare rheumatic diseases and CYCLOWVAS