Predicting Lupus Flare-Ups

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Scientists identify a new way to predict the severity of systemic lupus erythematosus symptoms.
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Like the ups and downs of a rollercoaster, many individuals with lupus experience alternating periods of remission, characterized by mild symptoms, followed by flare-ups with intensified and sometimes severe symptoms.

Researchers at the Schroeder Arthritis Institute have identified a blood-based biomarker that can predict future disease severity in patients with systemic lupus erythematosus (SLE).

SLE is the most common form of lupus—a chronic autoimmune disease in which the immune system attacks healthy tissues in the body. SLE can affect the joints, skin and organs.

There is no cure for SLE, but medications can reduce the frequency and severity of flare-ups. Currently, it is very challenging to predict when a patient is likely to experience periods of worsened symptoms and how severe they will be. This makes it difficult to administer therapies proactively.

To address this issue, a research team led by Dr. Joan Wither, a Senior Scientist at the Schroeder Arthritis Institute, set out to identify a biomarker that could predict the risk of flare-ups.

“Predicting the prognosis of SLE is extremely difficult,” explains Dr. Wither. “Being able to anticipate flare-ups would transform how we treat this disease.”

The researchers explored whether levels of type 1 interferons (IFNs)—a class of proteins involved in boosting the body’s immune response—could predict SLE severity. They studied type 1 IFNs because SLE symptoms have been linked to persistent immune system activation by these proteins.

IFNs function in the body by activating certain genes—known as IFN-responsive genes—within cells of the immune system. Because of this, the research team chose to look at the levels of these genes in individuals with SLE. The researchers tested the levels of five IFN-responsive genes in whole blood samples from 137 SLE patients and monitored these patients over five years. Each patient was assigned a score—called an IFN5 score—based on the levels of the five genes detected in their blood.

The team found that the IFN5 score was linked to disease severity over the five-year study period. Patients with high IFN5 scores were more likely to experience recurrent flare-ups and require increased or additional medications to treat their symptoms, compared to patients with low IFN5 scores.

“This finding is exciting because it means that a simple blood test could help determine how serious a patient’s symptoms will be over the next five years,” says Dr. Wither. “Patients with high IFN5 scores are likely to have more severe disease and flare-ups, so these patients might benefit from close monitoring and more aggressive treatments.”

This work was supported by the Canadian Institutes of Health Research, the Krembil Research Institute and the Toronto General & Western Hospital Foundation. PR Fortin holds a Tier 1 Canada Research Chair in Systemic Autoimmune Rheumatic Diseases at Université Laval.

Mai L, Asaduzzaman A, Noamani B, Fortin PR, Gladman DD, Touma Z, Urowitz MB, Wither J. The baseline interferon signature predicts disease severity over the subsequent 5 years in systemic lupus erythematosus. Arthritis Res Ther. 2021 Jan 16. doi: 10.1186/s13075-021-02414-0.

 

The senior author of the study, Dr. Joan Wither, is a Senior Scientist at the Schroeder Arthritis Institute, University Health Network.