Pathways in Inflammation study
Research type
Research Study
Full title
Pathways in Inflammation (PAIN) study
IRAS ID
330007
Contact name
Helen L Wright
Contact email
Sponsor organisation
University of Liverpool
Clinicaltrials.gov Identifier
23/PR/0783, PR Committee
Duration of Study in the UK
4 years, 11 months, 30 days
Research summary
Immune-mediated inflammatory diseases affect over 4 million people in the UK. These diseases arise from chronic inflammation which fails to resolve, and may include the generation of auto-antibodies. Cells of both the innate and adaptive immune system act together in the pathogenesis of immune-mediated inflammatory diseases. Production of neutrophil extracellular traps (NETs) by neutrophils can lead to exposure of auto-antigens to dendritic cells and auto-reactive B and T cells. This in turn drives cytokine secretion (e.g. interleukin-6, TNF-alpha) and development of auto-antibodies, which in then direct immune cells such as neutrophils and macrophages to attack host tissue (e.g. cartilage in RA, small blood vessels in the kidney in SLE). Whilst T cells and macrophages are a major source of inflammatory cytokines, neutrophils at the site of inflammation can damage host tissue through the release of reactive oxygen species (ROS) and proteases (elastase, collagenase). People with immune-mediated inflammatory diseases often have to take immune-suppressive medication and live for many years with pain, disability and multiple co-morbidities.
We, and others, have previously shown that immune cell signalling pathways are altered in inflammatory disease. For example, altered cell signalling leads to differences in neutrophil gene expression in RA and psoriatic arthritis. Signalling pathways involved in metabolism are altered in immune cells and extracellular biofluids (e.g. in synovial fluid and serum). These changes in cell signalling lead to altered cell functions, such as increased ROS and NET release that can damage tissues and drive inflammation.
In this study we will investigate the activation of signalling molecules and pathways in the blood of people with immune-mediated inflammatory disease. We will isolate different leukocyte populations from the blood to measure gene, protein and metabolite levels, and we will also isolation blood serum to measure extracellular protein and metabolite levels.REC name
West Midlands - Solihull Research Ethics Committee
REC reference
23/WM/0170
Date of REC Opinion
25 Aug 2023
REC opinion
Further Information Favourable Opinion