Delineating the B cell landscape in pediatric autoimmune diseases: insights and implications for Sjogren Syndrome, Systemic Lupus Erythematosus, and Juvenile Idiopathic Arthritis

The role of B cells is crucial but not fully understood in pediatric autoimmune diseases. This thesis presents comprehensive immunophenotypic analyses of B cell subsets in pediatric Sjogren Syndrome (pSS), childhood-onset Systemic Lupus Erythematosus (cSLE), and oligo- /poly-Juvenile Idiopathic Arthritis (JIA). Key findings suggest specific B cell abnormalities in pSS, such as increased atypical memory B cells and expanded T peripheral helper cells, which are unaffected by treatments. Elevated B-cell activating factor (BAFF) levels were noted in pSS, correlating with autoanitibodies and IgG production. Deficiencies in B cell tolerance checkpoints were also identified, pointing towards a less stringent tolerance checkpoints in pSS. B cell subset abnormalities were observed in cSLE, including reduced unswitched memory B cells and an increased frequency of double-negative (DN) B cells. A prominent type I and II interferon signature was detected in cSLE, suggesting a hyperactive IFN pathway. Interestingly, we found expanded a population of T-bet+ naïve B cells in cSLE, correlating with IFNg activity and clinical parameters. In JIA, a dysfunctional selection process in memory B cells and an expansion of TFH cells, with skewing immune responses towards IgG production, aberrant somatic hypermutation pattern, and altered B cell signaling point to a complex pathogenesis involving B cells. All in all, this study deepens our understanding of B cell dysregulation in pediatric autoimmune diseases and paves the way for developing novel targeted therapies in these diseases.