Role of the Nuclear Pore Component RANBP2 in Inflammatory Responses to Viral Infections
NCT ID: NCT06731790
Last Updated: 2026-02-05
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
NA
35 participants
INTERVENTIONAL
2025-04-24
2025-09-01
Brief Summary
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The primary endpoint in individuals in the "mutated RANBP2" arm is an inflammatory phenotype (hyperinflammatory monocytes, secretion of pro-inflammatory cytokines, anti-glycoprotein autoantibodies), significantly exacerbated basal and/or post-stimulation production of pro-inflammatory cytokines compared with the control arm.
The secondary objective is to examine the allelic expression of mutant RANBP2 and characterize genetic variants by whole-exome sequencing, in order to associate them with RANBP2 protein localization and ANE crisis severity
The researchers will compare the group of ANE1 patients with age- and sex-matched control groups, divided into two subgroups: unrelated controls and controls with familial ties. The aim is to study the different types of inflammatory responses and correlate them with the localization of the RANBP2 protein and the severity of ANE episodes.
Participants will participate in a single visit during which demographic data, clinical history and a blood test will be collected with one (unrelated control) or two blood tubes (ANE1 and related control).
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Detailed Description
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The research team have recently demonstrated that loss or mislocalisation of RANBP2, as seen with ANE-linked mutations, boosts influenza virus replication and triggers excessive inflammation.
The researchers hypothesis is that mutation of RANBP2 in ANE1 patients weakens nuclear pore control of innate immune signaling pathways, leading to an exacerbated inflammatory response to infections.
Conditions
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Study Design
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NON_RANDOMIZED
PARALLEL
BASIC_SCIENCE
NONE
Study Groups
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Mutant RANBP2 associated with predisposition to ANE1
Subjects aged 1 to 90 with a T585M mutation in RANBP2 for the "RANBP2 mutation" arm. During a single visit, 2 tubes of blood will be sampled, demographic data and clinical history collected, and a clinical examination performed.
Blood sampling for genetic analysis
Collection of a blood tube for whole exome sequencing, , long-read sequencing of the RANBP2 gene and analysis of the presence of the mutation by RTqPCR.
Blood sampling for inflammatory phenotype analysis
Blood sampling for basal and post-stimulation inflammatory phenotype analysis
Healthy control subjects
For healthy control subjects related to a person from the "mutant RANBP2" arm: During a single visit, 2 tubes of blood will be sampled, demographic data and clinical history collected, and a clinical examination performed. Healthy control subjects related to a person from the "mutant RANBP2" arm will be included in the third Secondary Outcome (whole exome sequencing).
For healthy control subjects unrelated to a person from the "mutant RANBP2" arm: During a routine epilepsy consultation for children, or a family disease screening for adults, an additional blood tube will be sampled, demographic data collected and a clinical examination performed. Healthy control subjects unrelated to a person from the "mutant RANBP2" arm will not be included in the third Secondary Outcome (whole exome sequencing).
Blood sampling for genetic analysis
Collection of a blood tube for whole exome sequencing, , long-read sequencing of the RANBP2 gene and analysis of the presence of the mutation by RTqPCR.
Blood sampling for inflammatory phenotype analysis
Blood sampling for basal and post-stimulation inflammatory phenotype analysis
Interventions
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Blood sampling for genetic analysis
Collection of a blood tube for whole exome sequencing, , long-read sequencing of the RANBP2 gene and analysis of the presence of the mutation by RTqPCR.
Blood sampling for inflammatory phenotype analysis
Blood sampling for basal and post-stimulation inflammatory phenotype analysis
Eligibility Criteria
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Inclusion Criteria
* Obtaining written consent from legal guardians of minors with their assent
* Subjects aged 1 to 90
* Subject with a T585M mutation in RANBP2 for the RANBP2 mutation arm.
* Subjects matched on age (+/- 10 years) and gender for the "control" arm.
Exclusion Criteria
* Absence of written informed consent
* Person unable to give consent
* legally protected adult (guardianship, curatorship)
* Person deprived of liberty
* Person participating in another research study with an exclusion period still in progress
1 Year
90 Years
ALL
Yes
Sponsors
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Institut de Recherche en Infectiologie de Montpellier (CNRS)
UNKNOWN
A*STAR Infectious Diseases Labs
INDUSTRY
University Hospital, Montpellier
OTHER
Responsible Party
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Principal Investigators
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Pierre MEYER, MD
Role: PRINCIPAL_INVESTIGATOR
Montpellier University Hospital
Locations
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CHU Gui de Chauliac
Montpellier, Hérault, France
Countries
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References
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Koh JC, Murugasu A, Krishnappa J, Thomas T. Favorable Outcomes With Early Interleukin 6 Receptor Blockade in Severe Acute Necrotizing Encephalopathy of Childhood. Pediatr Neurol. 2019 Sep;98:80-84. doi: 10.1016/j.pediatrneurol.2019.04.009. Epub 2019 Apr 25.
Bashiri FA, Al Johani S, Hamad MH, Kentab AY, Alwadei AH, Hundallah K, Hasan HH, Alshuaibi W, Jad L, Alrifai MT, Hudairi A, Al Sheikh R, Alenizi A, Alharthi NA, Abdelmagid TA, Ba-Armah D, Salih MA, Tabarki B. Acute Necrotizing Encephalopathy of Childhood: A Multicenter Experience in Saudi Arabia. Front Pediatr. 2020 Oct 9;8:526. doi: 10.3389/fped.2020.00526. eCollection 2020.
Okumura A, Mizuguchi M, Kidokoro H, Tanaka M, Abe S, Hosoya M, Aiba H, Maegaki Y, Yamamoto H, Tanabe T, Noda E, Imataka G, Kurahashi H. Outcome of acute necrotizing encephalopathy in relation to treatment with corticosteroids and gammaglobulin. Brain Dev. 2009 Mar;31(3):221-7. doi: 10.1016/j.braindev.2008.03.005. Epub 2008 May 5.
Mizuguchi M. Acute necrotizing encephalopathy of childhood: a novel form of acute encephalopathy prevalent in Japan and Taiwan. Brain Dev. 1997 Mar;19(2):81-92. doi: 10.1016/s0387-7604(96)00063-0.
Lim HY, Ho VP, Lim TC, Thomas T, Chan DW. Serial outcomes in acute necrotising encephalopathy of childhood: A medium and long term study. Brain Dev. 2016 Nov;38(10):928-936. doi: 10.1016/j.braindev.2016.05.002. Epub 2016 May 30.
Lee JH, Kim AJ, Kyong TY, Jang JH, Park J, Lee JH, Lee MJ, Kim JS, Suh YJ, Kwon SR, Kim CW. Evaluating the Outcome of Multi-Morbid Patients Cared for by Hospitalists: a Report of Integrated Medical Model in Korea. J Korean Med Sci. 2019 Jul 1;34(25):e179. doi: 10.3346/jkms.2019.34.e179.
Sell K, Storch K, Hahn G, Lee-Kirsch MA, Ramantani G, Jackson S, Neilson D, von der Hagen M, Hehr U, Smitka M. Variable clinical course in acute necrotizing encephalopathy and identification of a novel RANBP2 mutation. Brain Dev. 2016 Sep;38(8):777-80. doi: 10.1016/j.braindev.2016.02.007. Epub 2016 Feb 26.
Li J, Huo F, Wang S, Fan Y, Wu J, Zhang Z, Liu S, Wang Q. Recurrent infection triggered encephalopathy syndrome in a pediatric patient with RANBP2 mutation and severe acute respiratory syndrome coronavirus 2 infection. Pediatr Investig. 2023 Nov 19;7(4):290-296. doi: 10.1002/ped4.12406. eCollection 2023 Dec.
Jiang J, Wang YE, Palazzo AF, Shen Q. Roles of Nucleoporin RanBP2/Nup358 in Acute Necrotizing Encephalopathy Type 1 (ANE1) and Viral Infection. Int J Mol Sci. 2022 Mar 24;23(7):3548. doi: 10.3390/ijms23073548.
Levine JM, Ahsan N, Ho E, Santoro JD. Genetic Acute Necrotizing Encephalopathy Associated with RANBP2: Clinical and Therapeutic Implications in Pediatrics. Mult Scler Relat Disord. 2020 Aug;43:102194. doi: 10.1016/j.msard.2020.102194. Epub 2020 May 15.
Denier C, Balu L, Husson B, Nasser G, Burglen L, Rodriguez D, Labauge P, Chevret L. Familial acute necrotizing encephalopathy due to mutation in the RANBP2 gene. J Neurol Sci. 2014 Oct 15;345(1-2):236-8. doi: 10.1016/j.jns.2014.07.025. Epub 2014 Jul 18.
Neilson DE, Adams MD, Orr CM, Schelling DK, Eiben RM, Kerr DS, Anderson J, Bassuk AG, Bye AM, Childs AM, Clarke A, Crow YJ, Di Rocco M, Dohna-Schwake C, Dueckers G, Fasano AE, Gika AD, Gionnis D, Gorman MP, Grattan-Smith PJ, Hackenberg A, Kuster A, Lentschig MG, Lopez-Laso E, Marco EJ, Mastroyianni S, Perrier J, Schmitt-Mechelke T, Servidei S, Skardoutsou A, Uldall P, van der Knaap MS, Goglin KC, Tefft DL, Aubin C, de Jager P, Hafler D, Warman ML. Infection-triggered familial or recurrent cases of acute necrotizing encephalopathy caused by mutations in a component of the nuclear pore, RANBP2. Am J Hum Genet. 2009 Jan;84(1):44-51. doi: 10.1016/j.ajhg.2008.12.009.
Mizuguchi M, Abe J, Mikkaichi K, Noma S, Yoshida K, Yamanaka T, Kamoshita S. Acute necrotising encephalopathy of childhood: a new syndrome presenting with multifocal, symmetric brain lesions. J Neurol Neurosurg Psychiatry. 1995 May;58(5):555-61. doi: 10.1136/jnnp.58.5.555.
Desgraupes S, Etienne L, Arhel NJ. RANBP2 evolution and human disease. FEBS Lett. 2023 Oct;597(20):2519-2533. doi: 10.1002/1873-3468.14749. Epub 2023 Oct 15.
Stewart M. Polyadenylation and nuclear export of mRNAs. J Biol Chem. 2019 Mar 1;294(9):2977-2987. doi: 10.1074/jbc.REV118.005594. Epub 2019 Jan 25.
Other Identifiers
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RECHMPL23_0455
Identifier Type: -
Identifier Source: org_study_id
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