Synergistic immune dysregulation: Expansion of autoreactive B cells and Tfh/TPH cells and their clinical implications in childhood-onset lupus

Abstract

Objective

To delineate immunophenotypic alterations associated with newly diagnosed childhood-onset systemic lupus erythematosus (cSLE).

Methods

Peripheral blood from 25 newly diagnosed cSLE patients (ND-cSLEs) and 23 healthy controls (HCs) was examined by multiparameter flow cytometry to profile lymphocyte subsets and helper T-cell populations; serum cytokines were quantified by bead-based assays.

Results

Compared with HCs, ND-cSLEs exhibited cytopenias, reduced CD3⁺ and CD4⁺ T cells, a decreased CD4⁺/CD8⁺ ratio, and diminished NK cells. Autoreactive CD21^-CD27^-B cells and plasmablasts were markedly expanded, whereas naïve and memory B-cell compartments contracted. Both CD4⁺ and CD8⁺ T cells demonstrated increased PD-1 and HLA-DR expression, indicating concurrent activation and exhaustion. T peripheral helper cells and CXCR3⁺ Tfh cells were significantly enriched. Elevated serum IL-10, IL-8, and IL-21 levels further characterized the inflammatory milieu.

Conclusions

Newly Diagnosed cSLE patients is distinguished by profound remodeling of lymphocyte compartments, expansion of autoreactive and helper subsets, and heightened proinflammatory cytokine production, underscoring potential immunological biomarkers and therapeutic targets.