Alterations in peripheral blood B cell subsets and their clinical significance in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is characterized by B-cell dysregulation and autoantibody production. This study aimed to characterize the alterations in peripheral blood B-cell subsets across different states of SLE and to evaluate their diagnostic value and association with specific autoantibodies.A total of 84 participants were enrolled, comprising 64 SLE patients (including 20 newly diagnosed, 27 stable, and 17 with lupus nephritis) and 20 healthy controls (HCs). Peripheral blood B-cell subsets, including naïve B-cells, memory B-cells, and plasmablasts, were analyzed by flow cytometry. Their diagnostic performance was assessed using Receiver Operating Characteristic (ROC) curve analysis. Associations with anti-nuclear antibody (ANA), anti-dsDNA, and anti-Sm antibody status were also evaluated.Compared to HCs, SLE patients exhibited significant disturbances in B-cell homeostasis. The most consistent finding was a profound decrease in the absolute frequency of memory B cells across all patient groups (newly diagnosed, stable, and LN; all p < 0.001). Newly diagnosed patients showed a significant expansion of plasmablasts (p = 0.017), which was less pronounced in stable and LN groups. ROC analysis demonstrated that the absolute memory B-cell frequency (memory B%) had outstanding diagnostic performance for SLE (AUC = 0.905, 80% sensitivity, 80% specificity). Furthermore, higher anti-nuclear antibody (ANA) titers and anti-dsDNA positivity were significantly associated with a decreased absolute naïve B-cell count and an increased relative proportion of plasmablasts. Anti-Sm positivity was specifically linked to a higher plasmablast proportion (p = 0.006).Our findings highlight a marked disruption of peripheral B-cell subsets in SLE, particularly a persistent reduction in memory B cells and an expansion of plasmablasts in active disease. Memory B cells serve as an excellent diagnostic biomarker, while plasmablast expansion is closely associated with specific autoantibodies, underscoring the pivotal role of aberrant B-cell differentiation in SLE immunopathogenesis.