Role of the Nuclear Pore Component RANBP2 in Inflammatory Responses to Viral Infections (InflammaNUP)

February 2, 2026 updated by: University Hospital, Montpellier

The goal of this controlled, pathophysiological, exploratory interventional study is to compare the inflammatory phenotype of circulating immune cells, basal and following stimulation, from Acute Necrotizing Encephalopathy Type 1 (ANE1) patients with those from sex- and age-matched donors who do not carry the mutation.To date, no study has investigated the molecular mechanisms regulating the inflammatory response in ANE1 disease directly on patient samples.

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The nucleoporin RANBP2, also known as Nup358, is a component of the cytoplasmic filaments of nuclear pore complexes (NPCs), which regulate the transport of macromolecules between the cytoplasm and the nucleus. Mutations in the RANBP2 gene are associated with a rare genetic predisposition to acute necrotizing encephalopathy (ANE1), a predominantly pediatric disease characterized by multiple, symmetrical hemorrhagic lesions of the brain following febrile infection, most often with influenza A virus (IAV). Given the presumed inflammatory nature of ANE1, first-line treatment includes intravenous administration of high-dose pharmacological corticosteroids with or without immunoglobulins. In addition, two clinical cases report that IL-6 inhibition by tocilumizab may have a beneficial role.

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.

Study Type

Interventional

Enrollment (Actual)

35

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
    • Hérault
      • Montpellier, Hérault, France, 34295
        • CHU Gui de Chauliac

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Obtaining written consent from adult participants
  • 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:

  • Patient not affiliated to a social security scheme or not a beneficiary of such a scheme. (for example, a European Health Insurance Card (EHIC))
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Other: Blood sampling for inflammatory phenotype analysis
Blood sampling for basal and post-stimulation inflammatory phenotype analysis
Genetic: 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.
Active Comparator: 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).
Other: Blood sampling for inflammatory phenotype analysis
Blood sampling for basal and post-stimulation inflammatory phenotype analysis
Genetic: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Comparison of the inflammatory phenotype of circulating immune cells, both basal and following stimulation, from ANE1 patients with those from sex- and age-matched donors not carrying the mutation
Time Frame: Baseline

These experiments will be carried out on blood, serum, peripheral blood mononuclear cells (PBMC) and monocyte-derived macrophages and microglia (MDM and MMG, respectively).

The primary endpoint for individuals in the "mutated RANBP2" arm is an inflammatory phenotype, basal and/or after stimulation, that is significantly exacerbated compared with the "control" arms. Samples will be analyzed by ELISA/Luminex and flow cytometry. The expected difference will be a 2 to 10-fold upregulation in one or several markers of hyperinflammatory monocytes, and/or in one or several secreted pro-inflammatory cytokines, and/or in one or several autoantibodies, based on our results in PBMC treated with RANBP2-targeted RNA interference
Baseline

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Determination of the allelic expression of mutated RANBP2
Time Frame: Baseline
The first secondary endpoint will be heterozygous expression of mutated RANBP2 in individuals in the "mutated RANBP2" arm. The method of evaluation will be RT-PCR targeted to RANBP2, followed by quantitative PCR discriminating for the mutation, a diagnostic method recently introduced in the IRIM laboratory.
Baseline
Determination of the effect of the T585M heterozygous mutation on RANBP2 localization
Time Frame: Baseline
The second secondary outcome will be the significantly exacerbated basal and/or post-stimulation RANBP2 delocalization compared with the "control" arm. This will be tested on monocyte-derived macrophages by confocal microscopy.
Baseline
Characterization of genetic variants that are significantly associated with ANE seizure severity
Time Frame: Baseline
The third secondary endpoint will be the identification of genetic variants associated with the history of ANE episodes, if any, and their severity. The evaluation method will be whole exome sequencing, and long-read sequencing, only on participants from ANE families in the "control" and "mutated RANBP2" arms.
Baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Montpellier

Collaborators

A*STAR Infectious Diseases Labs
Institut de Recherche en Infectiologie de Montpellier (CNRS)

Investigators

  • Principal Investigator: Pierre MEYER, MD, Montpellier University Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 24, 2025

Primary Completion (Actual)

September 1, 2025

Study Completion (Actual)

September 1, 2025

Study Registration Dates

First Submitted

December 9, 2024

First Submitted That Met QC Criteria

December 9, 2024

First Posted (Actual)

December 12, 2024

Study Record Updates

Last Update Posted (Actual)

February 5, 2026

Last Update Submitted That Met QC Criteria

February 2, 2026

Last Verified

November 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RECHMPL23_0455

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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