Department of Gynecology, The First Affiliated Hospital, Zhejiang University of Medicine School, Zhejiang University, Hangzhou, China.
Department of Pathology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Clin Exp Immunol. 2020 Oct;202(1):72-79. doi: 10.1111/cei.13472. Epub 2020 Jul 6.
NOD-like receptor pyrin 7 (NLRP7) has been identified as the major gene responsible for the recurrent hydatidiform mole (RHM). The immunological role of NLRP7 mutation in HM patients has not been conclusively demonstrated. Hence, we aim to demonstrate this role in our study. We followed 12 new patients with NLRP7 non-synonymous variations (NSVs) from date to date. Peripheral blood mononuclear cells (PBMCs) were collected separately from patients with and without NLRP7 mutation. Supernatant interleukin (IL)-1β secretion, intracellular pro-IL-1β and mature IL-1β expressions were measured after 24 h lipopolysaccharide (LPS) stimulation. Plasmids with corresponding NSVs were generated to evaluate the ability of processing pro-IL-1β into mature IL-1β in vitro. Homozygous or compound heterozygous NLRP7 mutations secreted less IL-1β in roots of abnormal intracellular pro-IL-1β or mature IL-1β, according to different domains. Plasmids with NSVs could also affect processing or/and trafficking together with caspase-1 and apoptosis-associated speck-like protein (ASC). Inflammasome-related NLRP7 mutation is a potential mechanism of RHM.
核苷酸结合寡聚化结构域样受体热蛋白结构域包含蛋白 7（NLRP7）已被确定为导致复发性葡萄胎（RHM）的主要基因。 NLRP7 突变在 HM 患者中的免疫作用尚未得到明确证实。因此，我们旨在本研究中证明这一作用。我们对 12 名具有 NLRP7 非同义变异（NSV）的新患者进行了随访。分别从具有和不具有 NLRP7 突变的患者中采集外周血单核细胞（PBMC）。在 LPS 刺激 24 小时后，测量上清液中白细胞介素（IL）-1β的分泌，细胞内前 IL-1β和成熟 IL-1β的表达。生成具有相应 NSV 的质粒，以评估体外将 pro-IL-1β加工为成熟 IL-1β的能力。根据不同的结构域，纯合或复合杂合 NLRP7 突变导致异常细胞内 pro-IL-1β或成熟 IL-1β的根中 IL-1β分泌减少。具有 NSV 的质粒也可以与 caspase-1 和凋亡相关斑点样蛋白（ASC）一起影响加工和/或运输。炎症小体相关 NLRP7 突变是 RHM 的潜在机制。
