Objective: Pulmonary arterial hypertension (PAH) is an intractable complication in connective tissue diseases, but the pathological mechanisms responsible for progression remain obscure. This study aims to test whether patient IgG possesses biological activity promoting the migration of pulmonary artery smooth muscle cells (PASMCs).
Methods: Cell migration was estimated by lamellipodia formation and by utilizing a Boyden chamber method. The specificity of autoantibodies was established by western blotting, ELISA, and immunocytochemistry. The target antigen was investigated by mass spectrometry.
Results: IgG obtained from a patient with systemic lupus erythematosus (SLE) accompanied by PAH was found to promote lamellipodia formation and migration of PASMCs. The IgG bound to a ∼50 kDa protein expressed on the cell membrane, and in the cytoplasm and nucleus. This molecule was identified as enolase 1. Removal of enolase 1-binding antibodies from the IgG fraction, or treatment of the cells with an enolase inhibitor, significantly suppressed the migration of PASMCs.
Conclusion: Patients with SLE may possess autoantibodies to enolase 1 which stimulate the migration of PASMCs and are likely to play a role in the progression of PAH.
Keywords: Enolase 1; Pulmonary arterial hypertension; Pulmonary artery smooth muscle cells; Systemic lupus erythematosus.
Copyright © 2019 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.