NETPAD
Research type
Research Study
Full title
Exploring the characteristics and role of neutrophil extracellular trap formation as a potential target for the use of PAD inhibitors in rheumatic diseases.
IRAS ID
233894
Contact name
Raashid Luqmani
Contact email
Sponsor organisation
University of Oxford / Clinical Trials and Research Governance
Duration of Study in the UK
3 years, 1 months, 3 days
Research summary
The early response to inflammation is by the polymorphonuclear neutrophil (neutrophil), which is a common cell in the immune system responsible for defence against infection. However, the neutrophil is also involved in immune conditions and cancer. Neutrophils can release many products which can be helpful in defence against infection, but are usually harmful in patients with inflammatory conditions. One of the important features of neutrophils when they are activated is that they release some of their nuclear material (deoxyribonucleic acid, DNA) into their surroundings creating a "net" of proteins which can be up to 15 times as big as they are (also referred to as a Neutrophil Extracellular Trap, or NET) which is useful in catching and isolating infections. Unfortunately, this NET can also be involved in the development of immune conditions, because the DNA proteins which make up the net are not normally exposed to the immune system. The immune system can react to the proteins and this can be harmful. Many factors control neutrophils generation of NETs and this is likely to be important in many rheumatic conditions.
Some treatments affect NET production. The authors plan to test this in the laboratory by using neutrophils taken from patients with active inflammation from different rheumatic conditions (systemic lupus erythematosus [SLE], rheumatoid arthritis [RA] and vasculitis, an inflammation of blood vessels). Samples of blood from patients at different stages of activity (either very active disease or less active disease) will be compared with samples from healthy participants or with patients experiencing a generalised infection. The authors will use a variety of ways of checking how the neutrophils behave in the test tube, on their own or after stimulation, or after they have been exposed to compounds that inhibit some of their functions. There will be no additional treatment given to patients or the controls as part of the study. Any treatments that the patients require will be given to them as part of their standard care.
In this project the authors hope to be able to show that there is a role for NETs in these rheumatic conditions and whether or not they can interfere with the production of NETs by inhibiting specific enzymes (Peptidyl arginine deiminases, PADs). If this proves to be true, then inhibitors of PAD could be a future treatment which could be tested in a trial of patients with SLE, RA or vasculitis in the futureREC name
South Central - Hampshire B Research Ethics Committee
REC reference
18/SC/0375
Date of REC Opinion
11 Jul 2018
REC opinion
Favourable Opinion