此页面是自动翻译的，不保证翻译的准确性。请参阅 英文版 对于源文本。

由于自身抗体或遗传缺陷导致 I 型干扰素免疫力受损：前瞻性国家队列 (COVIFERON)

2026年9月15日 更新者：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.

研究概览

地位

招聘中

条件

干预/治疗

研究类型

观察性的

注册 (估计的)

500

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习联系方式

学习地点

  • 法国
      • Lille、法国
        • 招聘中
        • Cic Lille
        • 接触：
        • 副研究员：
          • Dominique DEPLANQUE, PU-PU
      • Lyon、法国
        • 招聘中
        • LYON HCL
        • 接触：
        • 副研究员：
          • Alexandre BELOT, PU-PU
      • Montpellier、法国
        • 招聘中
        • Cic Montpellier
        • 接触：
        • 副研究员：
          • Florence GALTIER, PH
      • Paris、法国
        • 招聘中
        • Cic Bichat
        • 接触：
        • 首席研究员：
          • Xavier-Marie DUVAL, PU-PU
      • Paris、法国
        • 招聘中
        • Cic Creteil
        • 接触：
        • 副研究员：
          • Philippe LE CORVOISIER, PU-PU
      • Paris、法国
        • 招聘中
        • Cic La Salpetriere
        • 接触：
        • 副研究员：
          • Joe-Elie SALEM, PU-PU
      • Paris、法国
        • 招聘中
        • Cic Necker
        • 接触：
        • 副研究员：
          • Michaela SEMERARO, PH
      • Paris、法国
        • 招聘中
        • Cic St Louis
        • 接触：
        • 副研究员：
          • Jean-Jacques KILADJIAN, PU-PU
      • Tours、法国
        • 招聘中
        • Cic Tours
        • 接触：
        • 副研究员：
          • Valérie GISSOT, PH

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年 及以上 (成人、年长者)

接受健康志愿者

是的

有资格学习的性别

全部

取样方法

非概率样本

研究人群

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).

描述

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

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 观测模型：COHORT
  • 时间观点：PROSPECTIVE

队列和干预

团体/队列
干预/治疗
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.
其他：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

研究衡量的是什么？

主要结果指标

结果测量
措施说明
大体时间
primary endpoint n°1 : quantitative dosage of auto-Abs against type I IFNs
大体时间：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
大体时间：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

次要结果测量

结果测量
措施说明
大体时间
Cumulative incidence of clinical events of interest, i.e. infectious events, autoimmune diseases or cancers
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

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

出版物和有用的链接

负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。

一般刊物

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (实际的)

2025年4月9日

初级完成 (估计的)

2029年1月1日

研究完成 (估计的)

2029年1月1日

研究注册日期

首次提交

2024年11月14日

首先提交符合 QC 标准的

2025年1月6日

首次发布 (实际的)

2025年1月7日

研究记录更新

最后更新发布 (实际的)

2026年9月18日

上次提交的符合 QC 标准的更新

2026年9月15日

最后验证

2026年9月1日

更多信息

与本研究相关的术语

关键字

其他相关的 MeSH 术语

其他研究编号

  • C22-73
  • 2023-A02663-42 (其他标识符：ANSM ID-RCB)

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)？

不

药物和器械信息、研究文件

研究美国 FDA 监管的药品

不

研究美国 FDA 监管的设备产品

不

此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.

订阅