Reduced plasmablast frequency is associated with seronegative myasthenia gravis. Issue 4 (24th December 2020)

• Record Type: Journal Article
• Authors: Guptill, Jeffrey T.; Barfield, Richard; Chan, Cliburn; Russo, Melissa A.; Emmett, Doug; Raja, Shruti; Massey, Janice M.; Juel, Vern C.; Hobson‐Webb, Lisa D.; Gable, Karissa L.; Gonzalez, Natalia; Hammett, Alex; Howard, James F.; Chopra, Manisha; Kaminski, Henry J.; Siddiqi, Zaeem A.; Migdal, Mattingly; Yi, John S.
• Is Part Of: Muscle & nerve. Volume 63:Issue 4(2021)
• Page Start: 577
• Page End: 585
• Publication Date: 2020-12-24
• Subjects: AChR -- biomarkers -- myasthenia gravis -- plasmablasts -- seronegative; Neuromuscular diseases -- Periodicals; Muscles -- Periodicals; Nerves -- Periodicals; 616.74
• DOI: 10.1002/mus.27140
• Languages: English
• ISSNs: 0148-639X

Abstract

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 − CD38 hi 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. Abstract : See Editorial on pages 439–441 in this issue .