Digital Modeling Illuminates Physiological Processes in Inflammatory Disease

Using digital models of a patient's unique disease mechanisms—so called digital twins—researchers at Karolinska Institute have obtained a deeper understanding of the “off and on” proteins that control inflammatory diseases like rheumatoid arthritis. The study, which was published in Cell Reports Medicine, could help facilitate the development of personalized drug therapies.

It is exceedingly difficult to diagnose and treat many inflammatory diseases as the pathological process varies from one patient to another with the same diagnosis, and even within the same patient at different times. In a project that has been underway for five years, researchers have been trying to solve this problem and tailor drugs to individual patients by constructing and studying their digital twins.

“Our analyses of patients who responded or didn’t respond to TNF therapy revealed different switch proteins in different individuals,” says the study’s corresponding author Mikael Benson. “Another important discovery was that the proteins did not switch off the diseases but were more like dimmer switches that raised or lowered the disease programs.”

This advanced digital modeling technique can help reveal a patient’s unique circumstances by analyzing the activity of each and every gene in thousands of individual cells from blood and tissue. Such a digital twin can be used to calculate the physiological outcome if a condition changes, such as the dosage of a drugs.

In the study, the researchers combined analyses of a mouse model of rheumatoid arthritis and digital twins of human patients with various inflammatory diseases.

“Even though only the joints were inflamed in mice, we found that thousands of genes changed their activity in different cell types in ten organs, including the skin, spleen, liver and lungs,” says Benson. “As far as I’m aware, this is the first time science has obtained such a broad picture of how many organs are affected in rheumatoid arthritis. This is partly due to the difficulty of physically sampling so many different organs.”