CD19+CD11c+T-bet+ B cells in myasthenia gravis: a potential biomarker

Background Myasthenia gravis (MG), an autoimmune disorder characterized by B cell-driven autoantibody production, exhibits heterogeneous B cell subsets dysregulation and incompletely defined signaling mechanisms. Methods A cohort of 20 naïve MG patients positive for anti-acetylcholine receptor (AChR) antibodies and 15 healthy controls was analyzed. Peripheral blood mononuclear cells underwent proteomic profiling, flow cytometry (age-associated B cells (ABCs), plasma cells, T follicular helper cells, and regulatory B cells), and western blot validation of nuclear factor kappa-B (NF-κB)/cellular reticuloendotheliosis oncogene homolog (c-Rel) expression. Clinical severity was assessed using quantitative MG (QMG) scores. Statistical analyses included differential protein expression, pathway enrichment, and receiver operating characteristic (ROC) curve evaluation. Results Proteomics revealed significant activation of the B cell receptor and NF-κB/c-Rel signaling pathways in MG patients, validated by upregulated NF-κB/c-Rel expression ( p < 0.01). Flow cytometry demonstrated elevated ABCs (CD19 + CD11c + T-bet + ), plasma cells, and T follicular helper cells, alongside reduced regulatory B cells in MG ( p < 0.001). The proportion of ABCs correlated positively with QMG scores ( r = 0.5015, p = 0.024) but not with AChR antibody titers, suggesting antibody-independent mechanisms. ROC analysis identified moderate diagnostic utility of ABCs for moderate-to-severe MG (QMG scores ≥ 6; area under the curve = 0.68, 95% confidence intervals: 0.42–0.94). Conclusion This study establishes ABCs and NF-κB/c-Rel signaling as central contributors to AChR-MG immunopathology. Therefore, ABCs may serve as complementary biomarkers for clinical stratification.