Refractory myasthenia gravis characterised by loss of regulatory T cells and expanded memory B cells

<h3></h3> It is not fully understood why many patients with Myasthenia Gravis (MG) are refractory to standard immunosuppressive therapy, and biomarkers to predict treatment outcome are lacking. We examined the circulating immune profile of those with MG of differing severity and treatment requirements to look for markers associated with refractory disease. Peripheral blood mononuclear cells and plasma were isolated from whole blood of 58 individuals with acetylcholine-receptor antibody positive MG of differing treatment requirements and 20 controls. Flow cytometry was used to determine cell frequencies and phenotypes. Refractory patients (n=10) demonstrate reduced regulatory T cell frequencies, which correlate negatively with disease severity and quality of life scores. Dendritic cell frequencies are also reduced in refractory cases, whereas monocytes are expanded. Additionally, there is expansion of memory B cells, mainly switched memory B cells expressing IgG, which is more pronounced in those with early- onset compared to late-onset MG. Preliminary stimulation studies have identified higher production of cytokines TNF-α, IL-6 and IL-10 from B cells in MG compared to control. Refractory MG is characterised by widespread immune changes that favour autoreactivity. These findings have important therapeutic implications as existing treatments are not designed to fully address these changes.