Determination of the trafficking kinetics and role of mononuclear phagocyte subsets in treatment-naive psoriatic arthritis.

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BackgroundPsoriatic arthritis is a condition caused by inflammation in the joints, leading them to become painful, stiff, and swollen. These symptoms are caused by immune system cells which travel into joints and cause damage. It can also cause other health problems, and a loss of about 3 years of life expectancy. The condition is expensive to treat, costing about £183 million per year to the NHS. The immune system is important in the development of psoriatic arthritis. Psoriatic arthritis is less studied than other conditions and this needs to be addressed.ContextThis research looks at a group of cells called "mononuclear phagocytes" which can attract and turn on other immune cells, causing a cycle of ongoing damage. Normally, immune cells move around the body in the blood, and only move into other places when they sense infection or damage. Healthy joints therefore contain few immune cells. In psoriatic arthritis, immune cells including mononuclear phagocytes move into the joints where they cause pain and damage. We do not understand what causes cells to move in this way. Identifying what causes the cells to move and controls their behaviour in the joint could provide a way of preventing immune cells from entering the joints, leading to new treatments. Recent advances in our understanding of mononuclear phagocytes have been made, including better ways to identify cells and discovery of new "inflammatory" cells important in other diseases. These findings have not been applied to arthritis. I aim to use the latest information and apply new techniques to better understand the behaviour of cells and track them in people with psoriatic arthritis. I will compare this against cells in the blood and joints of healthy people, and people with other forms of arthritis to see why psoriatic arthritis behaves differently.Research planI will identify and compare the immune cells in the blood and joints from clinical samples from arthritis clinics to those from people without arthritis, so our findings reflect real patients. I plan to investigate how the immune cells in the joints of people with arthritis are different from those without arthritis. I want to see which kinds of immune cells are in both the bloodstream and the joints, what the cells do in the joint, and what joint-damaging substances they release. This will tell us which immune cells are driving arthritis, how quickly they move from the blood into joints, and what makes the immune cells in psoriatic arthritis behave differently to those in healthy people. I will study the cells in the lab to determine how they interact with blood vessels to get into joints, and what joint-damaging substances they release when different triggers are applied. Finally, I will "tag" immune cells from participants so they can be seen using a special camera. These will then be reinjected into the bloodstream of the same person to watch how the cells move into the joints.Who and whereI will carry out this project at the University of Cambridge where we have developed the techniques to carry out these experiments. As well as being a researcher, I am a training rheumatologist, a doctor who specialises in joints and joint disease.ImportanceThis is a laboratory-based research study designed to understand how the cells that cause arthritis and its symptoms move into joints to trigger disease. This knowledge can then be used to design new treatments to stop or prevent immune cells from inappropriately entering joints. This may make treatments work better and reduce side-effects. The methods of "tagging" cells and seeing where they go in the body will also help to test if medications work for certain conditions. In addition, these findings may help understand other diseases where mononuclear phagocytes are important such as atherosclerosis and inflammatory bowel disease and develop new treatments for them.