Innately Adaptive or Truly Autoimmune: Is There Something Unique About Systemic Juvenile Idiopathic Arthritis?

Systemic juvenile idiopathic arthritis (JIA) is a form of arthritis in childhood that is initially dominated by innate immunity-driven systemic inflammation and is thus considered a polygenic autoinflammatory disease. However, systemic JIA can progress toward an adaptive immunity-driven afebrile arthritis. Based on this observation of biphasic disease progression, a window of opportunity for optimal, individualized and target-directed treatment has been proposed. This hypothesis requires testing, and in this review we summarize current evidence regarding molecular factors that may contribute to the progression from an initially predominantly autoinflammatory disease phenotype to autoimmune arthritis. We consider the involvement of innately adaptive gamma delta T cells and natural killer T cells that express gamma delta or alpha beta T cell receptors but cannot be classified as either purely innate or adaptive cells, versus classic B and T lymphocytes in this continuum. Finally, we discuss our understanding of how and why some primarily autoinflammatory conditions can progress toward autoimmune-mediated disorders over the disease course while others do not and how this knowledge may be used to offer individualized treatment.