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Immunità all'IFN di tipo I compromessa a causa di autoanticorpi o di un difetto genetico: una potenziale coorte nazionale (COVIFERON)

15 settembre 2026 aggiornato da: Institut National de la Santé Et de la Recherche Médicale, France

The major role of human genetic factors in the immune response to infections is now well established, particularly for viral infections. In the context of the COVID-19 pandemic, the following results have identified 1) several inborn errors of immunity (IEI) affecting the response or production of type I interferons (type I IFNs) in around 4% of adult patients with severe clinical disease, and 2) the presence of type I IFN-neutralizing autoantibodies (auto-Abs) in around 15% of severe cases, and 20% of deaths. The investigators would like to carry out a longitudinal immunological and clinical follow-up study on a prospective cohort of patients with either a genetic defect affecting the type I IFN-dependent immune response, or anti-IFN-I auto-Abs, to monitor the incidence of infectious and/or autoimmune events in these individuals, the evolution of neutralizing power, and the kinetics of auto-Abs. This should lead to a better understanding of the prevention and management of these patients.

The research design is a national multicenter prospective cohort of adults with 1) anti-IFN-I auto-Abs or 2) IEI- IFN-I, with follow-up from 1 to 4 years. These individuals may be: 1) patients who have or have had clinical disease (related to COVID-19, other viral infections, autoimmune disorders); or 2) "healthy" participants (e.g. blood donors, relatives of an IEI patient).

Follow-up will include:

  • yearly visits to the Clinical Investigation Center (CIC) or a clinical department with blood sampling;
  • specific visit in case of hospitalization for infectious events or adverse effects of vaccination, exacerbation or new diagnosis of auto-immune disease, new diagnosis of cancer, or SARS-CoV-2 infection whether or not patients are admitted to hospital, with blood sampling.

In addition, a retrospective "passive" follow-up will be implemented through matching with the data from the SNDS (National Health Data System), in order to collect clinical events of and healthcare resource consumption. Moreover, matching with controls adults from the national CONSTANCES cohort, not carrying auto-Abs against type I IFNs nor IEI-IFN-I, will be performed. (ratio 3:1; matching on age (+/- 5 years), gender and geographic region of recruitment). Individuals under long-lasting immunosuppressive or immunomodulatory drugs will not be eligible. Follow-up of controls, which will be carried out as part of the CONSTANCES cohort, will include web-based questionnaires, every 12 months, in addition to linking with SNDS data as already done in this cohort.

Inclusion visit:

After signing the consent form, the following tests will be performed:

  • Demographic characteristics (sex, age, country of birth)

  • Medical history from participant and family member(s) including infectious and auto-immune diseases, cancers and vaccination status and side effects

  • Blood samples for:

    • full blood cell count;

    • classical autoimmune investigations (anti-nuclear, anti-ENA, native anti-DNA, anti- thyroid antibodies, rheumatoid factor);

    • immunophenotyping*;

    • auto-Abs against type I IFNs, other cytokines*, or other target proteins* (dosage and neutralization activity);

    • Genetic explorations by whole-exome or whole-genome sequencing*;

    • Biobanking (DNA, plasma/sera; cryopreserved peripheral blood mononuclear cells (PBMCs).

      • these biological analyses will be carried out as part of dedicated COVIFERON RHU5 workpackages.

In addition, vaccination against SARS-CoV-2 and influenza will be offered to these subjects as a priority, as part of their usual care.

Follow-up visits :

Annual visits to the CIC :

  • Medical history since last visit, including infectious, auto-immune and oncologic events, vaccination status and side effects

  • Blood samples for:

    • full blood cell count;
    • classical autoimmune investigation (anti-nuclear, anti-ENA, native anti- DNA, anti-thyroid antibodies, rheumatoid factor);
    • immunophenotyping;
    • Auto-Abs against type I IFNs, other cytokines, or other target proteins (dosage and neutralization)
    • Biobanking (DNA, plasma, cryopreserved peripheral blood mononuclear cells (PBMCs))

Additional specific visit in the event of a clinical event of interest, at any time during follow-up:

  • In case of SARS-CoV-2 infection, whatever the severity of the disease: blood sampling for determination and neutralization of type I anti-IFN autoAbs, CBC, and biobanking (plasma and PBMC) and teleconsultation with the CIC in charge of patients, as soon as possible.
  • In the event of hospitalization for infectious events or exacerbation or new diagnosis of an auto-immune disease: blood sampling for determination and neutralization of anti-IFN-I autoAbs, CBC, and biobanking (plasma and PBMCs) and collection of the hospitalization report in the case report form on a dedicated page.

Panoramica dello studio

Stato

Reclutamento

Condizioni

Intervento / Trattamento

Tipo di studio

Osservativo

Iscrizione (Stimato)

500

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Contatto studio

Luoghi di studio

  • Francia
      • Lille, Francia
        • Reclutamento
        • Cic Lille
        • Contatto:
        • Sub-investigatore:
          • Dominique DEPLANQUE, PU-PU
      • Lyon, Francia
        • Reclutamento
        • LYON HCL
        • Contatto:
        • Sub-investigatore:
          • Alexandre BELOT, PU-PU
      • Montpellier, Francia
        • Reclutamento
        • Cic Montpellier
        • Contatto:
        • Sub-investigatore:
          • Florence GALTIER, PH
      • Paris, Francia
        • Reclutamento
        • Cic Bichat
        • Contatto:
        • Investigatore principale:
          • Xavier-Marie DUVAL, PU-PU
      • Paris, Francia
        • Reclutamento
        • Cic Creteil
        • Contatto:
        • Sub-investigatore:
          • Philippe LE CORVOISIER, PU-PU
      • Paris, Francia
        • Reclutamento
        • Cic La Salpetriere
        • Contatto:
        • Sub-investigatore:
          • Joe-Elie SALEM, PU-PU
      • Paris, Francia
        • Reclutamento
        • Cic Necker
        • Contatto:
        • Sub-investigatore:
          • Michaela SEMERARO, PH
      • Paris, Francia
        • Reclutamento
        • Cic St Louis
        • Contatto:
        • Sub-investigatore:
          • Jean-Jacques KILADJIAN, PU-PU
      • Tours, Francia
        • Reclutamento
        • Cic Tours
        • Contatto:
        • Sub-investigatore:
          • Valérie GISSOT, PH

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

18 anni e precedenti (Adulto, Adulto più anziano)

Accetta volontari sani

Sì

Sessi ammissibili allo studio

Tutto

Metodo di campionamento

Campione non probabilistico

Popolazione di studio

Adults with auto-Abs against IFN-I or an IEI-IFN-I who: 1) either have or have had a clinical disease (COVID-19 related, other viral infections, adverse effect of vaccination, auto-immune disorders); or 2) are healthy (e.g. blood donor, relatives of a participant).

Descrizione

Inclusion Criteria:

  • Age >18 years
  • History of carrying 1) auto-Abs against type I IFNs or 2) IEI impairing the response to, or the production of, type I IFNs (IFN-I-IEI)
  • Affiliated to social security
  • Written informed consent

Exclusion Criteria:

  • Participation to an interventional clinical trial on a pharmacological treatment
  • Clinical condition leading to life expectancy less than 1 year
  • Subject to a legal protection measure (safeguard of justice, curatorship, tutorship)
  • Individuals deprived of freedom

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Modelli osservazionali: COHORT
  • Prospettive temporali: PROSPECTIVE

Coorti e interventi

Gruppo / Coorte
Intervento / Trattamento
Subjects with auto-Abs against type I IFNs or inborn errors of immunity

The study examines how autoantibodies (auto-Abs) against type I interferons (IFNs) and inborn errors of immunity affect susceptibility to infectious diseases, especially COVID-19. Individuals with auto-Abs against type I IFNs have impaired immune responses to viral infections, putting them at higher risk for severe COVID-19, leading to worse outcomes like pneumonia or cytokine storms. Those with inborn errors of immunity have genetic defects that weaken immune function, increasing vulnerability to infections, including COVID-19. The study compares these groups to understand immune dysfunctions and identify potential therapeutic targets.
Altro: blood sample

After signature of consent form,blood samples will be collected for full blood cell count;classical autoimmune investigations, immunophenotyping;auto-Abs against type IIFNs, other cytokines, or other target proteins ,Genetic explorations by whole-exome or whole-genome sequencing;Biobanking

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
primary endpoint n°1 : quantitative dosage of auto-Abs against type I IFNs
Lasso di tempo: year 0, year 1, year 2 and year 3

Method: Quantitative trait will be measured by Gyros using commercially available internal control antibodies.
year 0, year 1, year 2 and year 3
primary endpoint n°2 : neutralization capacity evaluation of auto-Abs against type I IFNs
Lasso di tempo: year 0, year 1, year 2 and year 3

The neutralization capacity will be performed as previously reported using an in vitro luciferase system in HEK293 cells
year 0, year 1, year 2 and year 3

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Cumulative incidence of clinical events of interest, i.e. infectious events, autoimmune diseases or cancers
Lasso di tempo: Year 0, year 1, year 2 and year 3

Method: annual medical visits, SNDS (PMSI, DCIR). Incidence density rate is defined as the number of newly disease individuals on the sum of time periods for all disease-free individual-at-risk
Year 0, year 1, year 2 and year 3
Clinical and biological factors associated with clinical outcomes
Lasso di tempo: Year 0, year 1, year 2 and year 3

the potential predictor variables will be assessed by bivariate logistic regressions where occurrence of clinical events is the variable to be explained. Factors associated with a p-value less than 0.20 will be included in the multivariate logistic model. Backward selection on pvalue will be applied. Internal validity of the final model will be estimated by cross-validation (Leave-One-Out Cross-Validation method). Discrimination will be assessed by the area under the ROC curve and its 95% confidence interval.
Year 0, year 1, year 2 and year 3
Cumulative incidence of the same clinical events of interest, in control participants who are negative for auto-Abs, matched by age and sex followed through the large CONSTANCES cohort
Lasso di tempo: Year 0, year 1, year 2 and year 3

Cumulative incidence of the same clinical events of interest, in control participants who are negative for auto-Abs, matched by age and sex followed through the large CONSTANCES cohort (Constances database), and its 95% confidence interval: Incidence density rate is defined as the number of newly disease individuals on the sum of time periods for all disease-free individual-at-risk.
Year 0, year 1, year 2 and year 3
Genetic factors associated with the development of auto-Abs against type I IFNs
Lasso di tempo: Year 0, year 1, year 2 and year 3

searching for homozygous deletions using in-house HMZDelFinder-opt method of imagine institue
Year 0, year 1, year 2 and year 3
Genetic factors associated with the development of auto-Abs against type I IFNs
Lasso di tempo: year 0, year 1, year 2 and year 3

Searching for rare candidate coding variants in patients by following an optimal filtering strategy that imagine have optimized over the last 10 years based on multiple variant-level and gene-level criteria to select the candidate variants
year 0, year 1, year 2 and year 3
Genetic factors associated with the development of auto-Abs against type I IFNs
Lasso di tempo: year 0, year 1, year 2 and year 3

Using gene-level criteria to select candidate variants such as the negative selection level measured by the CoNeS approach.
year 0, year 1, year 2 and year 3

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Institut National de la Santé Et de la Recherche Médicale, France

Pubblicazioni e link utili

La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.

Pubblicazioni generali

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio (Effettivo)

9 aprile 2025

Completamento primario (Stimato)

1 gennaio 2029

Completamento dello studio (Stimato)

1 gennaio 2029

Date di iscrizione allo studio

Primo inviato

14 novembre 2024

Primo inviato che soddisfa i criteri di controllo qualità

6 gennaio 2025

Primo Inserito (Effettivo)

7 gennaio 2025

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

18 settembre 2026

Ultimo aggiornamento inviato che soddisfa i criteri QC

15 settembre 2026

Ultimo verificato

1 settembre 2026

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • C22-73
  • 2023-A02663-42 (Altro identificatore: ANSM ID-RCB)

Piano per i dati dei singoli partecipanti (IPD)

Hai intenzione di condividere i dati dei singoli partecipanti (IPD)?

NO

Informazioni su farmaci e dispositivi, documenti di studio

Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti

No

Studia un dispositivo regolamentato dalla FDA degli Stati Uniti

No

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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