Lymphocyte alterations and elevated complement signalling are key features of refractory myasthenia gravis

Abstract

BackgroundA significant proportion of patients with myasthenia gravis (MG) remain refractory to standard immunosuppressive therapy, and biomarkers to help guide treatment decisions are lacking. MethodsWe examined the circulating immune profile of patients with acetylcholine receptor antibody positive MG with differing treatment requirements and compared them to controls. FindingsRefractory patients displayed the highest frequency of memory B cells, and increased production of interleukin (IL)-6 and tumour necrosis factor (TNF)- upon toll-like receptor/ CD40 activation in vitro, mirrored by a dramatic loss of regulatory T cells (Tregs) and dendritic cells. Refractory MG was further characterised by elevated circulating complement proteins (C3, C5 and clusterin) and increased expression of complement receptors on lymphocytes. Following anti-CD20 therapy, residual plasmablasts persisted in circulation. Notably, a low baseline B cell frequency ( View larger version (34K): org.highwire.dtl.DTLVardef@13df9e2org.highwire.dtl.DTLVardef@1e086eborg.highwire.dtl.DTLVardef@1b9bb92org.highwire.dtl.DTLVardef@c9a164_HPS_FORMAT_FIGEXP M_FIG C_FIG