Interferon alpha: can it help us to predict response to lupus treatment?
Disease - Systemic lupus erythematosis
Lead applicant - Professor Claudia Mauri
Organisation - University College London
Type of grant - Invited Research Award
Status of grant - Active
Amount of the original award - £320,555
Start date - 1 October 2018
Reference - 21786
What are the aims of this research?
Lupus is an inflammatory autoimmune disease where the patient’s white blood cells (which normally serve to protect from infection) start to attack the body's own tissues. B cells are a particular type of white blood cells which are involved in the development of lupus. For this reason, removal of B cells from the immune system (using a treatment known as rituximab) is sometimes used to treat lupus. However, for unknown reasons, not all lupus patients respond well to rituximab treatment.
The aim of this research is to understand how a chemical messenger in the blood called interferon alpha (IFNα) influences how lupus progresses and whether levels of IFNα affect patients’ response to rituximab therapy.
Why is this research important?
Bregs are a type of good B cell that keep the immune system in check in healthy individuals. In lupus patients with severe disease, Bregs are not present and this contributes to disease. The researchers have previously found that lupus patients with severe disease have higher levels of a chemical messenger in the blood, known as IFNα. They believe that this messenger prevents the formation of “good” Bregs, while promoting the formation of other “bad” B cells. The researchers predict that lupus patients with high levels of IFNα are less likely to respond to rituximab because, after rituximab treatment ends, B cells return to the immune system but less of these B cells are able to turn into good; Bregs.
In this research, people with lupus will be screened before and after rituximab treatment to measure how much IFNα and how many “good” Bregs and “bad” B cells they have in their blood. Further work will look directly at how B cells respond to increasing amounts of IFNα and whether other molecules can keep Bregs working properly in lupus patients. The researchers will also look at how IFNα affects the DNA of B cells from lupus patients that do not respond well to rituximab therapy.
How will the findings benefit patients?
At present, not all lupus patients respond to rituximab, and there is no way of knowing which patients will respond. Understanding how the levels of IFNα in patients affect the formation of Bregs, and thus the response to rituximab, will be critical in helping to decide which patients will respond appropriately to treatment with rituximab. This will provide a more effective way of guiding doctors about the choice of treatment for their patients.