The primary focus of the Schulert lab is the pathogenesis of severe inflammatory disorders of childhood, in particular systemic juvenile idiopathic arthritis (systemic JIA). Although systemic JIA is considered a subtype of JIA, it has distinct clinical and epidemiologic characteristics, notably prominent extra-articular features, including prolonged spiking fevers, rash, lymphadenopathy and serositis. The pathogenesis of systemic JIA is incompletely understood, but recent work suggests that it fits the paradigm of autoinflammatory disorders. In contrast to classic autoimmune disorders, which are associated by autoreactive, antigen-specific T cells and autoantibodies, autoinflammatory disorders display abnormal activation of innate immune effector cells, most notably monocytes/macrophages and neutrophils.
Children with systemic JIA are at high risk for life threatening complications, including macrophage activation syndrome (MAS) and chronic lung disease. MAS is a potentially life-threatening episode of overwhelming inflammation occurring in 10-30% of systemic JIA patients, and is characterized by fevers, cytopenias, coagulopathy, liver and central nervous system dysfunction, and a systemic cytokine storm. Chronic lung disease (SJIA-LD) is a recently recognized and poorly understood complication that has emerged as a key driver of systemic JIA morbidity and mortality. The long-term goal of the lab is to determine the course and pathophysiology of severe complications of systemic JIA, leading to targeted therapy that improves patient outcomes.