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

Date Published: 2025-08-22

Abstract:
Myasthenia gravis (MG), an autoimmune disorder characterized by B cell-driven autoantibody production, exhibits heterogeneous B cell subsets dysregulation and incompletely defined signaling mechanisms. 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-?B)/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. Proteomics revealed significant activation of the B cell receptor and NF-?B/c-Rel signaling pathways in MG patients, validated by upregulated NF-?B/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). This study establishes ABCs and NF-?B/c-Rel signaling as central contributors to AChR-MG immunopathology. Therefore, ABCs may serve as complementary biomarkers for clinical stratification.

Introduction:
Myasthenia gravis (MG), an autoimmune disorder characterized by B cell-driven autoantibody production, exhibits heterogeneous B cell subsets dysregulation and incompletely defined signaling mechanisms.

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