Department of Immunopathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
HiPep Laboratories, Kyoto, Japan.
Immunol Lett. 2020 Feb;218:22-29. doi: 10.1016/j.imlet.2019.12.005. Epub 2019 Dec 19.
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).
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.
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.
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.
肺动脉高压（PAH）是结缔组织疾病的一种难治性并发症，但导致其进展的病理机制仍不清楚。本研究旨在检测患者 IgG 是否具有促进肺动脉平滑肌细胞（PASMC）迁移的生物学活性。
通过片状伪足形成和 Boyden 室法来评估细胞迁移。通过 Western blot、ELISA 和免疫细胞化学来确定自身抗体的特异性。通过质谱法来研究靶抗原。
从患有伴有 PAH 的系统性红斑狼疮（SLE）的患者中获得的 IgG 被发现可促进 PASMC 的片状伪足形成和迁移。该 IgG 与细胞膜上表达的约 50 kDa 的蛋白结合，并且在细胞质和核内结合。该分子被鉴定为烯醇化酶 1。从 IgG 部分去除烯醇化酶 1 结合抗体，或用烯醇化酶抑制剂处理细胞，可显著抑制 PASMC 的迁移。
患有 SLE 的患者可能具有针对烯醇化酶 1 的自身抗体，这些抗体可刺激 PASMC 的迁移，并可能在 PAH 的进展中发挥作用。
