Immunopathogenesis

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