Research & Discovery

UVA researchers identify cells driving life-threatening scleroderma

University of Virginia School of Medicine researchers have uncovered a possible way to prevent the dangerous hardening of skin and organs in people with systemic scleroderma, a rare autoimmune disease.

The research shows that a certain type of immune cell plays a direct role in creating thick scar tissue that damages organs in people with the disease. Systemic scleroderma often proves deadly, with more than 30% of patients dying within 10 years, frequently because scarring stiffens the lungs and makes breathing difficult.

UVA researcher Blandine Baffert, working in the lab of UVA Health’s Sanja Arandjelovic and collaborating with researchers in France, found immune cells known as macrophages are responsible for the harmful buildup of fibrous scar tissue in patients with systemic scleroderma.

Although no treatments currently exist to prevent tissue and organ hardening in people with the disease, the team stopped the scarring in lab mice by targeting macrophages. The findings identify a new treatment strategy and may have broader implications for it and other diseases marked by chronic inflammation and scarring.

Portrait of UVA Health scientist Sanja Arandjelovic (left) and UVA researcher Blandine Baffert (right)

UVA Health scientist Sanja Arandjelovic, left, and UVA researcher Blandine Baffert, right, are studying treatment strategies for systemic scleroderma by targeting macrophages that drive harmful collagen buildup and scarring. (Left, contributed photo; right, photo by Tom Daly)

“Although more research is needed on understanding whether targeting these cells later during disease progression can reverse the existing tissue damage, our data suggest that macrophage inhibition could be effective in disease prevention in the high-risk patient population,” said Arandjelovic, of UVA’s Division of Nephrology and UVA’s Center for Immunity, Inflammation and Regenerative Medicine.

Who is at risk

Systemic scleroderma affects women more often than men and most commonly appears between the ages of 30 and 50. People of African and Choctaw Native American descent face a higher risk of developing the disease. An estimated 100,000 Americans live with systemic scleroderma, while about 200,000 more have a milder, localized form of the condition that affects specific areas of the body and is far less likely to be life-threatening.

For people with systemic scleroderma, the skin and organs harden because the body makes too much collagen – a material that normally helps hold skin, bones and connective tissue together. Arandjelovic and her team found macrophages drive this process as they respond to ongoing inflammation.

In healthy situations, these cells calm down once inflammation fades. But in people with systemic scleroderma, the inflammation never stops, causing the cells to keep producing collagen until it starts to damage the body.

What comes next

In laboratory studies, the researchers used two different methods to dial back macrophage activity. Both approaches completely stopped the harmful scarring.

Based on those results, the team believes a future treatment for systemic scleroderma could focus on limiting the buildup of macrophages or blocking the substances they release that drive excess collagen production.

“Clinically approved therapies that target macrophages already exist,” Arandjelovic said. “Repurposing these treatments for use in scleroderma would be an exciting next step in finding new therapies for this devastating disease.”