Infection and Immunity

Juvenile idiopathic arthritis (JIA) is a chronic autoimmune disease that represents the most common rheumatic condition in children. JIA is characterized by a chronic inflammatory process affecting the synovia. Although the underlying disease etiology remains poorly understood, dysregulated innate and adaptive immune responses have been identified to contribute to disability and loss of quality of life. B cells and their secreted antibodies play a crucial role in enabling the molecular recognition of a wide range of self and foreign molecular structures (antigens). B cells and their secreted antibodies have been implicated in JIA pathophysiology and the presence of autoantibodies has suggested a breakdown in B cell tolerance. Additionally, there have been reports of altered B cell subsets both within the synovial fluid and the peripheral blood in JIA. Importantly, the recent success of treating JIA with rituximab, a B cell depletion therapy, further supports the potential and promise of B cell intervention to improve clinical outcomes. Although there is mounting evidence that B cells and autoantibodies play a role in JIA pathophysiology, a comprehensive understanding of B cell phenotype, antibody sequence, and antibody function remains lacking in both peripheral blood and synovial fluid B cell niches. Furthermore, it remains unknown whether these signatures can distinguish subtypes of JIA and how these B cell populations are influenced following therapeutic intervention. In this PhD, we will integrate computational and experimental methodologies to investigate how B cell phenotype, antibody sequence and antibody function are altered during JIA and subsequent treatment efforts. With this knowledge, we aim to elucidate fundamental mechanisms of B cell selection in JIA, discover immune recognition at the single-cell level, and computationally predict disease outcome and improve patient stratification.

Contact
Enno Grosse Wichtrup