Investigation of Somatic Defects in Patients with Autoimmune Diseases
Megan Cooper, M.D., Ph.D.
Pediatrics, Pathology and Immunology
- Center for Metabolism and Immunity
- McDonnell Pediatric Cancer Center
Interdisciplinary Research Initiative
2/1/2012 - 1/31/2016
John P. Atkinson, Todd Druley
Pediatric autoimmune diseases such as systemic lupus erythematosus are often difficult to diagnose and can have devastating long-term effects on health including chronic arthritis, organ damage, cardiovascular disease, and mortality. Recent studies have shown that some pediatric patients with autoimmune lymphoproliferative syndrome (ALPS), a disease characterized by multiple autoimmune abnormalities and an increased risk of cancer, acquire “somatic” genetic defects in their immune cells. This means that the gene causing the disease is only abnormal in some immune cells, but is normal in other healthy cells from the same patient. Dr. Cooper hypothesizes that somatic genetic defects may be a more broadly applicable mechanism of autoimmune disease.. Dr. Cooper’s project will investigate whether pediatric patients with other autoimmune diseases that share clinical features of ALPS, including systemic lupus erythematosus and mixed connective tissue disease, have abnormal immune cells with somatic genetic defects. Aims: 1) Identify abnormal immune cells subsets present in the blood of patients with pediatric-onset autoimmune disease. 2) Evaluate the function of these immune cells in pediatric patients with autoimmune diseases. 3) Use next generation DNA sequencing to investigate whether somatic genetic defects of abnormal immune cells might contribute to the development of pediatric autoimmune disease. Potential impact: We anticipate that this research will lead to new approaches for diagnosis, monitoring, and treatment of pediatric autoimmune diseases within the next 10 years.