CD19+CD11c+T-bet+ B cells in myasthenia gravis: a potential biomarker
BackgroundMyasthenia gravis (MG), an autoimmune disorder characterized by B cell-driven autoantibody production, exhibits heterogeneous B cell subsets dysregulation and incompletely defined signaling mechanisms.MethodsA cohort of 20 naïve MG patients positive for anti-acetylcholine receptor (AChR) a...
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Frontiers Media S.A.
2025-08-01
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| Series: | Frontiers in Neurology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fneur.2025.1623066/full |
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| author | Yaru Lu Huimin Shen Yiye Wang Kai Ma Ruihua Sun Ying Zhao Yaqiong Li Qian Ma Jiewen Zhang |
| author_facet | Yaru Lu Huimin Shen Yiye Wang Kai Ma Ruihua Sun Ying Zhao Yaqiong Li Qian Ma Jiewen Zhang |
| author_sort | Yaru Lu |
| collection | DOAJ |
| description | BackgroundMyasthenia gravis (MG), an autoimmune disorder characterized by B cell-driven autoantibody production, exhibits heterogeneous B cell subsets dysregulation and incompletely defined signaling mechanisms.MethodsA 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.ResultsProteomics 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).ConclusionThis 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. |
| format | Article |
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| institution | Kabale University |
| issn | 1664-2295 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Neurology |
| spelling | doaj-art-d0f6a5c4dd284f08bf75514e70e91bcc2025-08-22T08:08:25ZengFrontiers Media S.A.Frontiers in Neurology1664-22952025-08-011610.3389/fneur.2025.16230661623066CD19+CD11c+T-bet+ B cells in myasthenia gravis: a potential biomarkerYaru Lu0Huimin Shen1Yiye Wang2Kai Ma3Ruihua Sun4Ying Zhao5Yaqiong Li6Qian Ma7Jiewen Zhang8Department of Neurology, Zhengzhou University People’s Hospital, Henan Provincial People’s Hospital, Zhengzhou, ChinaDepartment of Neurology, Zhengzhou University People’s Hospital, Henan Provincial People’s Hospital, Zhengzhou, ChinaDepartment of Neurology, Zhengzhou University People’s Hospital, Henan Provincial People’s Hospital, Zhengzhou, ChinaDepartment of Neurology, Zhengzhou University People’s Hospital, Henan Provincial People’s Hospital, Zhengzhou, ChinaDepartment of Neurology, Zhengzhou University People’s Hospital, Henan Provincial People’s Hospital, Zhengzhou, ChinaDepartment of Neurology, Zhengzhou University People’s Hospital, Henan Provincial People’s Hospital, Zhengzhou, ChinaDepartment of Neurology, Zhengzhou University People’s Hospital, Henan Provincial People’s Hospital, Zhengzhou, ChinaDepartment of Neurology, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, ChinaDepartment of Neurology, Zhengzhou University People’s Hospital, Henan Provincial People’s Hospital, Zhengzhou, ChinaBackgroundMyasthenia gravis (MG), an autoimmune disorder characterized by B cell-driven autoantibody production, exhibits heterogeneous B cell subsets dysregulation and incompletely defined signaling mechanisms.MethodsA 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.ResultsProteomics 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).ConclusionThis 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.https://www.frontiersin.org/articles/10.3389/fneur.2025.1623066/fullmyasthenia gravisNF-κB pathwayage-associated B cellsproteomicsflow cytometry |
| spellingShingle | Yaru Lu Huimin Shen Yiye Wang Kai Ma Ruihua Sun Ying Zhao Yaqiong Li Qian Ma Jiewen Zhang CD19+CD11c+T-bet+ B cells in myasthenia gravis: a potential biomarker Frontiers in Neurology myasthenia gravis NF-κB pathway age-associated B cells proteomics flow cytometry |
| title | CD19+CD11c+T-bet+ B cells in myasthenia gravis: a potential biomarker |
| title_full | CD19+CD11c+T-bet+ B cells in myasthenia gravis: a potential biomarker |
| title_fullStr | CD19+CD11c+T-bet+ B cells in myasthenia gravis: a potential biomarker |
| title_full_unstemmed | CD19+CD11c+T-bet+ B cells in myasthenia gravis: a potential biomarker |
| title_short | CD19+CD11c+T-bet+ B cells in myasthenia gravis: a potential biomarker |
| title_sort | cd19 cd11c t bet b cells in myasthenia gravis a potential biomarker |
| topic | myasthenia gravis NF-κB pathway age-associated B cells proteomics flow cytometry |
| url | https://www.frontiersin.org/articles/10.3389/fneur.2025.1623066/full |
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