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Abnormal processing of IL-1β in NLRP7-mutated monocytes in hydatidiform mole patients
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  • jianhua qian,
  • peiwen zhang,
  • xiaoxu zhu,
  • xinying yu,
  • Bo Huang,
  • Tingting Jiang
jianhua qian
Zhejiang University School of Medicine First Affiliated Hospital
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peiwen zhang
Zhejiang University School of Medicine First Affiliated Hospital
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xiaoxu zhu
Zhejiang University School of Medicine First Affiliated Hospital
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xinying yu
Zhejiang University School of Medicine First Affiliated Hospital
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Bo Huang
Zhejiang University School of Medicine First Affiliated Hospital
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Tingting Jiang
Zhejiang University School of Medicine First Affiliated Hospital
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Abstract

Background 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. Methods We followed 12 new patients with NLRP7 nonsynonymous variations (NSVs) from date to date. Peripheral blood mononuclear cells (PBMCs) were collected from patients with and without NLRP7 mutation, separately. Supernatant IL-1β secretion, intracellular pro-IL-1β and mature-IL-1β expressions were measured after 24h lipopolysaccharide (LPS) stimulation. Plasmids with corresponding NSVs were generated to evaluate the ability of processing pro-IL-1β into mature-IL-1β in vitro. Results Homozygous or compound heterozygous NLRP7 mutation secreted less IL-1β in root of abnormal intracellular pro-IL-1β or mature-IL-1β according to different domain defective. Plasmids with NSVs could also affect processing or/and trafficking together with caspase-1 and apoptosis-associated speck-like protein (ASC). Conclusion Inflammasome related NLRP7 mutation is a potential mechanism of RHM.

Peer review status:ACCEPTED

30 Jan 2020Submitted to Clinical & Experimental Immunology
03 Feb 2020Submission Checks Completed
03 Feb 2020Assigned to Editor
17 Feb 2020Reviewer(s) Assigned
13 Mar 2020Review(s) Completed, Editorial Evaluation Pending
13 Apr 2020Editorial Decision: Revise Minor
27 Apr 20201st Revision Received
28 Apr 2020Reviewer(s) Assigned
26 May 2020Review(s) Completed, Editorial Evaluation Pending
26 May 2020Editorial Decision: Accept