Juvenile idiopathic arthritis (JIA) is a the most common form of arthritis in children and affects approximately 50,000 individuals in the United States alone. Previous research suggested that autoimmune responses cause JIA, but the specific antigens that are responsible for driving autoimmunity have not been identified. In this month's issue of JCI Insight, Laura Santambrogio of the Albert Einstein College of Medicine and her colleagues report that the molecular chaperone transthyretin (TTR) acts an antigen that stimulates B and T cell immune responses. They identified TTR by profiling the proteins present in the synovial fluid of patients with JIA. The researchers found that some patients had elevated levels of TTR in synovial joint fluid, with TTR frequently occurring in aggregated forms. They subsequently demonstrated that patients with elevated levels of TTR had higher levels of TTR autoantibodies present. In addition, 3 out of 17 JIA patients showed T cell responses to TTR, including increased cytokine production and T cell proliferation. The research team also recapitulated the T cell responses to TTR in a humanized mouse model. Collectively, this study identifies autoimmune responses to TTR in a subset of JIA patients and suggests that aggregated forms of TTR can trigger disease development.
Source: Journal of Clinical Investigation