Jeffrey T Guptill1,2, Richard Barfield3, Cliburn Chan3, Melissa A Russo1, Doug Emmett1, Shruti Raja1, Janice M Massey1, Vern C Juel1, Lisa D Hobson-Webb1, Karissa L Gable1, Natalia Gonzalez1, Alex Hammett2, James F Howard4, Manisha Chopra4, Henry J Kaminski5, Zaeem A Siddiqi6, Mattingly Migdal7, John S Yi8. 1. Neuromuscular Division, Department of Neurology, Duke University Medical Center, Durham, North Carolina, USA. 2. Duke Clinical Research Institute, Durham, North Carolina, USA. 3. Department of Biostatistics and Bioinformatics, Duke University, Durham, North Carolina, USA. 4. Neuromuscular Disorders Section, Department of Neurology, The University of North Carolina, Chapel Hill, North Carolina, USA. 5. Department of Neurology, George Washington University, Washington, District of Columbia, USA. 6. Division of Neurology, University of Alberta, Edmonton, Alberta, Canada. 7. The University of North Carolina, Chapel Hill, North Carolina, USA. 8. Division of Surgical Sciences, Department of Surgery, Duke University Medical Center, Durham, North Carolina, USA.
Abstract
BACKGROUND: The immunopathology of autoimmune seronegative myasthenia gravis (SN MG) is poorly understood. Our objective was to determine immune profiles associated with a diagnosis of SN MG. METHODS: We performed high-dimensional flow cytometry on blood samples from SN MG patients (N = 68), healthy controls (N = 46), and acetylcholine receptor antibody (AChR+) MG patients (N = 27). We compared 12 immune cell subsets in SN MG to controls using logistic modeling via a discovery-replication design. An exploratory analysis fit a multinomial model comparing AChR+ MG and controls to SN MG. RESULTS: An increase in CD19+ CD20- CD38hi plasmablast frequencies was associated with lower odds of being a SN MG case in both the discovery and replication analyses (discovery P-value = .0003, replication P-value = .0021). Interleukin (IL) -21 producing helper T cell frequencies were associated with a diagnosis of AChR+ MG (P = .004). CONCLUSIONS: Reduced plasmablast frequencies are strongly associated with a SN MG diagnosis and may be a useful diagnostic biomarker in the future.
BACKGROUND: The immunopathology of autoimmune seronegative myasthenia gravis (SN MG) is poorly understood. Our objective was to determine immune profiles associated with a diagnosis of SN MG. METHODS: We performed high-dimensional flow cytometry on blood samples from SN MG patients (N = 68), healthy controls (N = 46), and acetylcholine receptor antibody (AChR+) MG patients (N = 27). We compared 12 immune cell subsets in SN MG to controls using logistic modeling via a discovery-replication design. An exploratory analysis fit a multinomial model comparing AChR+ MG and controls to SN MG. RESULTS: An increase in CD19+ CD20- CD38hi plasmablast frequencies was associated with lower odds of being a SN MG case in both the discovery and replication analyses (discovery P-value = .0003, replication P-value = .0021). Interleukin (IL) -21 producing helper T cell frequencies were associated with a diagnosis of AChR+ MG (P = .004). CONCLUSIONS: Reduced plasmablast frequencies are strongly associated with a SN MG diagnosis and may be a useful diagnostic biomarker in the future.
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