ORIGINAL RESEARCH article
Front. Neurol.
Sec. Neuromuscular Disorders and Peripheral Neuropathies
Volume 16 - 2025 | doi: 10.3389/fneur.2025.1623066
CD19 + CD11c + T-bet + B cells in myasthenia gravis: A potential biomarker
Provisionally accepted
Yaru Lu1,2*
Huimin Shen1,2Yiye Wang1,2
Kai Ma1,2
Ruihua Sun1,2
Ying Zhao1,2
Yaqiong Li1,2Qian Ma3
Zhang Jiewen1,2- 1Department of Neurology, People's Hospital of Zhengzhou University, Zhengzhou, China
- 2Department of Neurology, Henan Provincial People's Hospital, Zhengzhou, China
- 3Department of Neurology, The Fifth Afffliated Hospital, Sun Yat-sen University, Zhuhai, China
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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). Conclusions: 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.
Keywords: Myasthenia Gravis, NF-κB pathway, Age-associated B cells, Proteomics, Flow Cytometry
Received: 05 May 2025; Accepted: 29 Jul 2025.
Copyright: © 2025 Lu, Shen, Wang, Ma, Sun, Zhao, Li, Ma and Jiewen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yaru Lu, Department of Neurology, People's Hospital of Zhengzhou University, Zhengzhou, China
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