An observational study in Immunology, Allergy and Genetic Diseases, sponsored by Institut National de la Santé Et de la Recherche Médicale, France. Recruiting at 9 sites in France. Open to participants aged 18 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-09-18.
Sponsored by Institut National de la Santé Et de la Recherche Médicale, France · Observational
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:
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:
Blood samples for:
Biobanking (DNA, plasma/sera; cryopreserved peripheral blood mononuclear cells (PBMCs).
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 :
Blood samples for:
Additional specific visit in the event of a clinical event of interest, at any time during follow-up:
1,055 studies on the registry are indexed under Hypersensitivity; 149 are open to participants now.
This study's planned enrollment of 500 is above the median of 166 across 327 observational studies indexed under Hypersensitivity.
Browse Hypersensitivity studies →Institut National de la Santé Et de la Recherche Médicale, France is the lead sponsor of 378 studies on the registry; 81 are open to participants now.
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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).
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Life expectancy
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Other: 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
primary endpoint n°1 : quantitative dosage of auto-Abs against type I IFNs
Method: Quantitative trait will be measured by Gyros using commercially available internal control antibodies.
Time frame: year 0, year 1, year 2 and year 3
primary endpoint n°2 : neutralization capacity evaluation of auto-Abs against type I IFNs
The neutralization capacity will be performed as previously reported using an in vitro luciferase system in HEK293 cells
Time frame: year 0, year 1, year 2 and year 3
Cumulative incidence of clinical events of interest, i.e. infectious events, autoimmune diseases or cancers
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
Time frame: Year 0, year 1, year 2 and year 3
Clinical and biological factors associated with clinical outcomes
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.
Time frame: 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
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.
Time frame: Year 0, year 1, year 2 and year 3
Genetic factors associated with the development of auto-Abs against type I IFNs
searching for homozygous deletions using in-house HMZDelFinder-opt method of imagine institue
Time frame: Year 0, year 1, year 2 and year 3
Genetic factors associated with the development of auto-Abs against type I IFNs
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
Time frame: year 0, year 1, year 2 and year 3
Genetic factors associated with the development of auto-Abs against type I IFNs
Using gene-level criteria to select candidate variants such as the negative selection level measured by the CoNeS approach.
Time frame: year 0, year 1, year 2 and year 3
Plan to share: No
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