Impaired Type I IFN Immunity Due to Autoantibodies or a Genetic Defect: a Prospective National Cohort
Impaired Type I IFN Immunity Due to Autoantibodies or a Genetic Defect: a Prospective National Cohort
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:
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).
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:
Additional specific visit in the event of a clinical event of interest, at any time during follow-up:
Inclusion Criteria:
Exclusion Criteria:
xavier.duval@aphp.fr01 40 25 71 48
Lille, France
dominique.deplanque@univ-lille.fr03 20 44 68 91
alexandre.belot@chu-lyon.fr04 27 85 61 26
f-galtier@chu-montpellier.fr04 67 33 23 29
xavier.duval@aphp.fr01 40 25 71 48
philippe.lecorvoisier@aphp.fr06 88 25 81 15
joe-elie.salem@aphp.fr01 42 17 85 31
michaela.semeraro@aphp.fr01 42 19 27 16
jean-jacques.kiladjian@aphp.fr01 42 49 94 94
valerie.gissot@univ-tours.fr02 34 37 96 53