Circulating CXCR5+ natural killer cells are expanded in patients with myasthenia gravis

Abstract

Objectives

Myasthenia gravis (MG) is a classic autoantibody-mediated disease in which pathogenic antibodies target postsynaptic membrane components, causing fluctuating skeletal muscle weakness and fatigue. Natural killer (NK) cells are heterogeneous lymphocytes that have gained increasing attention owing to their potential roles in autoimmune disorders. This study will investigate the relationship between the distinct NK cell subsets and MG pathogenesis.

Methods

A total of 33 MG patients and 19 healthy controls were enrolled in the present study. Circulating NK cells, their subtypes and follicular helper T cells were analysed by flow cytometry. Serum acetylcholine receptor (AChR) antibody levels were determined by ELISA. The role of NK cells in the regulation of B cells was verified using a co-culture assay.

Results

Myasthenia gravis patients with acute exacerbations had a reduced number of total NK cells, CD56^dim NK cells and IFN-γ-secreting NK cells in the peripheral blood, while CXCR5⁺ NK cells were significantly elevated. CXCR5⁺ NK cells expressed a higher level of ICOS and PD-1 and a lower level of IFN-γ than those in CXCR5⁻ NK cells and were positively correlated with Tfh cell and AChR antibody levels. In vitro experiments demonstrated that NK cells suppressed plasmablast differentiation while promoting CD80 and PD-L1 expression on B cells in an IFN-γ-dependent manner. Furthermore, CXCR5⁻ NK cells inhibited plasmablast differentiation, while CXCR5⁺ NK cells could more efficiently promote B cell proliferation.

Conclusion

These results reveal that CXCR5⁺ NK cells exhibit distinct phenotypes and functions compared with CXCR5⁻ NK cells and might participate in the pathogenesis of MG.