Can specific types of immune cells lead to worsening symptoms?

Autoimmune diseases can affect individuals differently. For example, two people with the same autoimmune disease can exhibit different symptoms and experience flares at different rates. As a result, treatments can vary and become complicated. Fortunately, a research team from Japan discovered that increased levels of certain immune cells may be responsible for the different levels of presentation of an autoimmune disease called systemic sclerosis (or scleroderma).

A study waiting to be published in Nature Communications revealed that the variation in disease severity among systemic sclerosis patients appears to be linked to the proliferation of specific immune cells in critical organs. Systemic sclerosis is an autoimmune, rheumatic, and chronic disease that affects the body by hardening connective tissues. This autoimmune disease can also cause issues in the blood vessels, organs, and digestive tract.

To explore why the symptoms and level of organ involvement vary from patient to patient, researchers took blood and tissue samples from patients with systemic sclerosis to analyze for differences in gene expression. In doing this, they identified the EGR1-expressing subpopulation of CD14+ monocytes, a specific subset of immune cells associated with kidney complications in individuals with systemic sclerosis. These CD14+ monocytes transformed into destructive white blood cells called macrophages, which can increase inflammation near the kidneys and play a role in the scarring of internal organs.

The researchers also discovered that CD8+ T cells exhibiting a type II interferon signature—known to make immune cells highly aggressive and inflammatory—were associated with the worsening of interstitial lung disease. Additionally, EGR1-expressing CD14+ monocytes and these distinct CD8+ T cells are believed to accumulate in the kidney and lung, respectively, where they may generate or attract other elements that drive disease progression.

By identifying these types of cells, researchers can better understand which patients are at higher risk and work toward developing treatments that directly target the cells responsible.