Investigating lack of response to rituximab in Sjogren’s syndrome
Disease - Sjögren’s syndrome
Lead applicant - Dr Elena Pontarini
Organisation - William Harvey Research Institute
Type of grant - Foundation Fellowship
Status of grant - Active
Amount of the original award - £204,218.38
Start date - 2 January 2018
Reference - 21753
What are the aims of this research?
A recent clinical trial (TRACTISS) funded by Versus Arthritis aimed to assess the use of rituximab for Sjögren’s syndrome. The results of this study indicated that rituximab is neither clinically effective nor cost-effective in this group of patients. Therefore, in this project, the researchers are going to investigate why this is the case, using biological samples collected in the trial, both before and after treatment.
Why is this research important?
In some conditions, B cells in the body produce harmful autoantibodies which attack the body's own tissues. Rituximab is a type of biological therapy that removes B cells, and is used to treat conditions such as rheumatoid arthritis and vasculitis. This research will help understand why many patients with Sjögren’s syndrome do not respond to B cell removal.
The research will mainly focus on the balance between a subset of immune cells, which promote inflammation, and their counterpart which promote resolution of inflammation. The researchers wish to demonstrate that patients with Sjögren’s syndrome have an imbalance of these two types of immune cells, which causes persistent inflammation in the salivary glands and contributes to the lack of response to rituximab.
How will the findings benefit patients?
Understanding the mechanisms of response and resistance to rituximab in Sjögren’s syndrome could lead to new treatment targets for the condition, and may also allow the identification of a responsive subset of patients. In addition, there are currently two large clinical trials in Sjögren’s syndrome ongoing in the UK targeting molecules that will be studied as part of this research. Therefore, not only could the research contribute to a better understanding of the disease, but it could also facilitate the progression of the ongoing clinical trials in this area.