This study will explore whether a form of autoimmune arthritis that occurs in children is produced when innate immune white blood cells remain activated and resist the normal processes of cell death, while regulatory immune cells fail to intercede. If so, the findings may lead to improved means to diagnose and treat this autoimmune disorder.
Systemic juvenile idiopathic arthritis (SJIA) is a chronic inflammatory disease of childhood. Not only does the inflammation damage the membrane surrounding joints, producing arthritis, but it also damages the membrane surrounding the heart and lungs. About 25,000 children in this country have SJIA, and about five percent of them die of complications. The Stanford researchers hypothesize that this autoimmune disease is produced by two factors. First, innate immune white blood cells, called “monocytes,” remain activated for a prolonged time and stimulate inflammation, while managing to avoid the normal process (called “apoptosis”) that leads to the death of activated cells. Second, regulatory immune T cells fail to prevent or curtail activation of the monocytes.
The investigators will test this hypothesis in serial blood samples from 45 children with SJIA in different stages of the disease: those on medication who are having disease flare-ups, those on medication whose disease is in a quiet stage, and those patients who are in remission—a temporary lessening of symptoms or even disappearance of the disease—without medication. Findings will be compared to 35 children with a related arthritic condition that affects multiple joints but not the heart and lung membranes and to 30 healthy volunteers. Through this comparison, the researchers would identify monocyte and regulatory T cell abnormalities that not only occur during active SJIA disease but also persist in patients who are in remission, suggesting that these are the abnormalities responsible for the disease.
Significance: This study may identify specific defects in immune white blood cells and regulatory T cells that underlie susceptibility to this systemic autoimmune disease of childhood, providing targets for immunotherapies designed to prevent or treat this autoimmune disease.