Reduced plasmablast frequency is associated with seronegative myasthenia gravis.

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. See Editorial on pages 439–441 in this issue. [ABSTRACT FROM AUTHOR]