Investigating mechanisms of early disease that control inflammatory arthritis progression

Disease - Rheumatoid arthritis

Lead applicant - Dr Gareth Jones

Organisation - University of Bristol

Type of grant - Career Development Fellowship

Status of grant - Active

Amount of the original award - £384,952.65

Start date - 1 July 2013

Reference - 20305

Public Summary

What are the aims of this research?

Inflamed joint tissue from patients with early arthritis often displays clusters of immune cells, called germinal centres, which drive rapid disease progression. This research project aims to understand how germinal centres drive the disease process in early inflammatory arthritis, whether a molecule called IL-27 has potential to predict and prevent the development of these structures and also which currently available treatments are most successful at blocking germinal centre formation.

Why is this research important?

Clusters of immune cells called germinal centres normally only form in organs that contribute to the body's defence against infection, such as the lymph nodes and spleen. However, they are also found in the joints of over 25% of patients with early inflammatory arthritis, where they act as a local command centre to drive disease progression. In order to achieve remission, it is essential that treatment starts early in the course of disease, before significant joint damage has occurred. Finding clinical markers which indicate the presence of germinal centres would allow these patients to be identified early in disease development, allowing prompt treatment.

A protein called IL-27 has been shown to block the development of germinal centres. Levels of this molecule are either very low or absent completely in early arthritis patients with these structures. These findings suggest that IL-27 may be able to block germinal centre development and also that levels of this molecule could be used as a clinical marker to indicate their development.

How will the findings benefit patients?

Understanding how germinal centres develop in early inflammatory arthritis may improve diagnosis and lead to the development of new treatments for patients with these structures in their joints.