Juvenile-onset systemic sclerosis (jSSc) is a rare, life-threatening autoimmune disease associated with multi-organ inflammation, which results in collagen overproduction as well as thickening and scarring of connective tissue. Systemic sclerosis may cause thickened skin over all parts of the body and affect the joints, heart, lungs, intestinal tract, kidneys, and/or blood vessels. The cause of systemic sclerosis (SSc) is not known, but specific blood and immune cells are believed to be involved. Treatments are often immunosuppressive medications, which present significant risks to the body’s organs and are often ineffective. While jSSc resembles adult-onset SSc, there are differences in the diseases including which blood proteins and antibodies are present and which organs are typically affected. Most SSc research has focused on the adult-onset form; therefore, much remains unknown about jSSc.

We are in a unique position to address this knowledge gap due to our pediatric scleroderma clinic that attracts patients worldwide, collaborative clinicians and researchers with rheumatology and transplant expertise, and cutting-edge technology to discover new specific targets for treatment. A stem cell transplant treatment protocol was recently developed and implemented at our institution to improve clinical outcomes for jSSc patients by resetting the immune system, which has been shown to halt thickening and scarring of connective tissue as soon as 6 months post-transplant. Treatment involves patients receiving medicines that suppress the immune system, then receiving an infusion of their own stem cells, which is administered much like a blood transfusion. Patients are at risk for infections due to their suppressed immune system for several months after the transplant but should require less immunosuppressive medications over time, which would lessen the long-term risks for infection and organ damage.

Focus areas that will be addressed in our study: (1) Defining multi-omics, cellular, and patient-reported outcome biomarkers to inform clinical care. (2) Developing pilot clinical trial platforms to compare therapeutic approaches.

Our objective is to identify cellular and molecular (DNA and RNA) differences within blood cells and skin before and after stem cell transplant, which will allow us to explore and identify key cells and molecular changes involved in jSSc disease. These cellular and molecular differences will be compared to evaluations of the patients’ organ function and quality of life. This will allow us to determine the most significant changes and identify appropriate targeted treatment. Our long-term goal is to develop new treatments that will slow or stop disease progression, and thus improve both quality of life and long-term patient outcomes.