D1.498 - Altered B Cell Dynamics in Childhood-Onset Systemic Lupus Erythematosus: Insights from Disease States and Rituximab Treatment

Childhood-onset Systemic Lupus Erythematosus (cSLE) is characterized by more severe organ involvement and higher disease activity compared to adult-onset SLE. B cells play a central role in SLE pathogenesis. While B-cell-targeting therapies like Rituximab (RTX) are used as adjuvant treatments, a subset of patients still experiences flares. This study aimed to investigate the dynamics of B-cell subpopulations across different disease states and evaluate how these changes correlate with clinical responses to RTX.

We prospectively enrolled 57 cSLE patients at National Taiwan University Hospital since January 2023. B-cell subpopulations (including transitional, naive, memory B cells, and plasmablasts) were analyzed using flow cytometry (CD19, CD27, IgD, CD38, CD24, CD21 markers). Clinical disease activity was assessed using SLEDAI-2K and ESR. In patients receiving adjuvant RTX (375 mg/m per dose), B-cell dynamics were monitored at 1–3 months and 6–12 months post-infusion to evaluate treatment response.

• B Cells as Activity Biomarkers: In patients not treated with RTX, total B-cell ratio significantly correlated with disease activity markers, including SLEDAI-2K (P=0.0011) and ESR (P=0.0056). Active disease states were associated with higher percentages of total B cells and a trend toward increased plasmablasts (P=0.0563).
• RTX Treatment Response: RTX effectively reduced total B cells and memory subsets. However, patients with progressive disease (non-responders) 6–12 months post-RTX exhibited a higher median B-cell repopulation ratio (12.2%) compared to responders (9.0%).
• Predictors of Outcome: Inadequate B-cell depletion at 1–3 months post-RTX was significantly associated with progressive disease (P=0.0390). Additionally, high BAFF levels were observed in some patients with clinical flares, potentially contributing to treatment resistance.

B-cell dynamics, particularly the total B-cell ratio, serve as valuable biomarkers for disease severity in cSLE. Monitoring the depth of B-cell depletion and the pace of repopulation can aid in predicting the efficacy of RTX treatment and move toward more personalized therapeutic strategies.