Investigation of genetic susceptibility markers to arthritic conditions and how they contribute to disease

Study code

Lead researcher
Dr Annie Yarwood

Study type
Participant re-contact

Institution or company
University of Manchester

Researcher type

Speciality area
Musculoskeletal Disorders


The study was set up to investigate how a change in DNA which can increase a person’s risk of developing juvenile idiopathic arthritis (JIA) affects the cells of the immune system. One specific change in DNA which increases the risk of JIA, has been shown to alter the response of T-cells after stimulation. This is important as T-cells keep our immune system healthy. If they do not respond in a normal way then the immune system can become imbalanced and result in disease.

Blood samples were collected from people who have a specific change in their DNA. Cells were extracted from the blood samples and have been stored at -150°C ready for analysis. The cells will be looked at using a technology called CyTOF. This will allow us to look at all the different types of T cells in the blood in detail, and to see if people with specific changes in their DNA have changes in their T cells.

This research is still on going as the principle investigator has been on maternity leave and work has been affected by the pandemic. Our hypothesis is that changes in the DNA alter the number and function of a specific type of T cell called T-regulatory cells. These cells are the regulators of the immune system. When the immune system is activated by a virus or bug your immune cells fight this infection. When the infection has been dealt with, T-regulatory cells dampen down the immune response and restore the normal balance. Without T-regulatory cells the immune system would go into overdrive. JIA is an autoimmune disease, this means that the immune system is in overdrive and is attacking the joints. There is evidence to suggest that this maybe because T-regulatory cells are not working properly to prevent this.

If our hypothesis is correct and changes in the DNA, which increase the risk of developing JIA, alter the number and function of a specific type of T cell called T-regulatory cells. It has been shown that this can be corrected by giving cells a protein called IL-2. We believe that IL-2 could be used as a treatment for JIA to restore T-regulatory cells and restore the immune balance. Once they study is complete we will publish our results. In parallel to this we are also hoping to set up a clinical trial of IL-2 in JIA. We are very grateful to the individual volunteers from the NIHR BioResource who provided blood samples to enable us to undertake this work.

Participation: For this study we recruited 12 volunteers to give a 100ml blood sample.

Organisation: This study is organised by Professor Jane Worthington from the University of Manchester.