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자가항체 또는 유전적 결함으로 인한 제1형 IFN 면역 장애: 유망한 국립 코호트 (COVIFERON)

2026년 9월 15일 업데이트: 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.

연구 개요

상태

모병

정황

개입 / 치료

연구 유형

관찰

등록 (추정된)

500

연락처 및 위치

이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.

연구 연락처

연구 장소

  • 프랑스
      • Lille, 프랑스
        • 모병
        • Cic Lille
        • 연락하다:
        • 부수사관:
          • Dominique DEPLANQUE, PU-PU
      • Lyon, 프랑스
        • 모병
        • LYON HCL
        • 연락하다:
        • 부수사관:
          • Alexandre BELOT, PU-PU
      • Montpellier, 프랑스
        • 모병
        • Cic Montpellier
        • 연락하다:
        • 부수사관:
          • Florence GALTIER, PH
      • Paris, 프랑스
        • 모병
        • Cic Bichat
        • 연락하다:
        • 수석 연구원:
          • Xavier-Marie DUVAL, PU-PU
      • Paris, 프랑스
        • 모병
        • Cic Creteil
        • 연락하다:
        • 부수사관:
          • Philippe LE CORVOISIER, PU-PU
      • Paris, 프랑스
        • 모병
        • Cic La Salpetriere
        • 연락하다:
        • 부수사관:
          • Joe-Elie SALEM, PU-PU
      • Paris, 프랑스
        • 모병
        • Cic Necker
        • 연락하다:
        • 부수사관:
          • Michaela SEMERARO, PH
      • Paris, 프랑스
        • 모병
        • Cic St Louis
        • 연락하다:
        • 부수사관:
          • Jean-Jacques KILADJIAN, PU-PU
      • Tours, 프랑스
        • 모병
        • Cic Tours
        • 연락하다:
        • 부수사관:
          • Valérie GISSOT, PH

참여기준

연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.

자격 기준

공부할 수 있는 나이

18년 이상 (성인, 고령자)

건강한 자원 봉사자를 받아들입니다

예

연구 대상 성별

모두

샘플링 방법

비확률 샘플

연구 인구

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).

설명

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

공부 계획

이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.

연구는 어떻게 설계됩니까?

디자인 세부사항

  • 관찰 모델: COHORT
  • 시간 관점: PROSPECTIVE

코호트 및 개입

그룹/코호트
개입 / 치료
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.
다른: 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

연구는 무엇을 측정합니까?

주요 결과 측정

결과 측정
측정값 설명
기간
primary endpoint n°1 : quantitative dosage of auto-Abs against type I IFNs
기간: 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
기간: 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

2차 결과 측정

결과 측정
측정값 설명
기간
Cumulative incidence of clinical events of interest, i.e. infectious events, autoimmune diseases or cancers
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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

공동 작업자 및 조사자

여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.

스폰서

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

간행물 및 유용한 링크

연구에 대한 정보 입력을 담당하는 사람이 자발적으로 이러한 간행물을 제공합니다. 이것은 연구와 관련된 모든 것에 관한 것일 수 있습니다.

일반 간행물

연구 기록 날짜

이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.

연구 주요 날짜

연구 시작 (실제)

2025년 4월 9일

기본 완료 (추정된)

2029년 1월 1일

연구 완료 (추정된)

2029년 1월 1일

연구 등록 날짜

최초 제출

2024년 11월 14일

QC 기준을 충족하는 최초 제출

2025년 1월 6일

처음 게시됨 (실제)

2025년 1월 7일

연구 기록 업데이트

마지막 업데이트 게시됨 (실제)

2026년 9월 18일

QC 기준을 충족하는 마지막 업데이트 제출

2026년 9월 15일

마지막으로 확인됨

2026년 9월 1일

추가 정보

이 연구와 관련된 용어

키워드

추가 관련 MeSH 약관

기타 연구 ID 번호

  • C22-73
  • 2023-A02663-42 (기타 식별자: ANSM ID-RCB)

개별 참가자 데이터(IPD) 계획

개별 참가자 데이터(IPD)를 공유할 계획입니까?

아니요

약물 및 장치 정보, 연구 문서

미국 FDA 규제 의약품 연구

아니

미국 FDA 규제 기기 제품 연구

아니

이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .

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