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.