REF-VALUE Study: Establishment of Reference Values for Biomarkers in Healthy Adults (REF-VALUE Stud)

Circulating biomarkers play a central role in translational research and precision medicine, particularly for the diagnosis, prognostic, monitoring of inflammatory or infectious diseases and patient stratification. Advances in analytical technologies enable standardised, sensitive and multiplexed assays, but their application remains limited by the lack of reliable reference values derived from well-characterised healthy populations. Indeed, the available data are often heterogeneous and difficult to transfer between platforms.

In this context, the establishment of institutional reference cohorts appears essential for the correct interpretation of immunological parameters-which could be strongly influenced by demographic and clinical factors-and for defining relevant cut-off values when identifying new biomarkers of interest. This issue is particularly critical in the field of viral respiratory infections, where current diagnostic approaches still have several limitations.

Circulating biomarkers play a central role in translational research and precision medicine, particularly for the diagnosis, prognostic, monitoring of inflammatory or infectious diseases and patient stratification. Advances in analytical technologies enable standardised, sensitive and multiplexed assays, but their application remains limited by the lack of reliable reference values derived from well-characterised healthy populations. Indeed, the available data are often heterogeneous and difficult to transfer between platforms.

In this context, the establishment of institutional reference cohorts appears essential for the correct interpretation of immunological parameters-which could be strongly influenced by demographic and clinical factors-and for defining relevant cut-off values when identifying new biomarkers of interest. This issue is particularly critical in the field of viral respiratory infections, where current diagnostic approaches still have several limitations.

Diagnosis is usually based on PCR tests targeting the DNA or RNA of pathogens, requiring a virus-specific test. In practice, only a few viruses (SARS-CoV-2, RSV, influenza) are tested for as a first-line investigation, whilst many other agents may be involved. As a comprehensive approach is difficult to achieve, viral infections often remain under-reported.

Furthermore, the detection of a virus by PCR may indicate either an active infection or residual traces of a past infection. Although viral load can aid interpretation, it does not always allow for a definitive conclusion, making it difficult to distinguish between ongoing viral replication and the persistence of genetic material. It is therefore necessary to have additional markers associated with active infection.

In this context, analysing the host response represents a promising alternative. Viruses induce, in particular, the production of type I interferons (IFN-I), the measurement of which could point the diagnosis towards a viral origin and reflect ongoing infectious activity. However, the interpretation of these biomarkers requires robust reference standards, taking into account their variability across individuals and contexts.

Several studies illustrate the value of such approaches, such as the REFIPA study (NCT07239830), conducted in subjects over 80 years of age, which aims to characterise the immune response, particularly IFN-I, in the context of immunosenescence. This type of study highlights the need for well-phenotyped healthy ? control populations according to age groups and clinical contexts.

Finally, beyond the creation of reference databases, the development of biobanks appears essential. This would enable the establishment of harmonised and directly usable reference values, thereby facilitating translational, basic and pre-clinical research projects, as well as the identification and validation of new biomarkers.

Study Overview

• Status: Not yet recruiting
• Conditions: Uninfected Healthy Adult Subjects
• Intervention / Treatment: Biological: Biological Sampling

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sophie TROUILLET-ASSANT; Phone Number: +33 4 72 67 87 80; Email: sophie.trouillet-assant@chu-lyon.fr
• Study Contact Backup: Name: William MOUTON; Phone Number: +33 4 72 67 87 85; Email: william.mouton@chu-lyon.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Participants aged between 18 and 65 years (inclusive)
• Participants with no known medical conditions
• Body weight of 50 kg or more

Exclusion Criteria:

• Participants with symptoms of an active infection (symptom questionnaire or temperature > 37.5°C).

  • Subjects participating in another interventional study with an exclusion period that is still ongoing or that may interfere with this protocol
  • Pregnant women, women in labour or breastfeeding women
  • Individuals deprived of their liberty by a judicial or administrative decision
  • Individuals receiving psychiatric care
  • Individuals admitted to a health or social care facility for purposes other than research
  • Adults subject to legal protection measures (guardianship, curatorship)
  • Individuals not affiliated with a social security scheme or beneficiaries of a similar scheme

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Healthy volunteers; Healthy, uninfected adults aged 18 to 65 inclusive. Participants may be recruited through the press and social media, via the staff mailing list of the Hospices Civils de Lyon, or via posters displayed within the hospital aimed at staff, as well as at patients' carers and any other interested individuals.

Biological: Biological Sampling; The procedures specifically carried out for the study are as follows: 1 nasopharyngeal swab for baseline measurement of the nasal IFN score and to detect the presence of infection; Venous blood sample collection:1 x 2.5 mL PAXgene tube for baseline measurement of the blood IFN score1 x 4 mL dry tube (serum) to quantify anti-IFN antibody levels1 x 4 mL heparinized tube to assess non-specific functional immunity.1 x 2 mL EDTA tube for quantification of circulating leukocyte populations via complete blood count (CBC)1 x 2 mL EDTA tube for quantification of the main circulating lymphocyte subpopulations via immunophenotyping2 x 10 mL EDTA tubes and 1 x 4 mL EDTA tube for collection of PBMCs and plasma for biobanking A total of 38.5 mL of venous blood will be collected for the study during a single visit. This volume complies with regulations for subjects weighing at least 50 kg (eligibility criterion).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To establish reference values for the nasal and blood type I interferon score in an uninfected adult population aged 18 to 65 years inclusive.	The primary endpoint is the measurement of nasal and blood interferon levels in a population of uninfected adults aged 18 to 65 years inclusive.	One day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the impact of immune parameters on baseline blood and nasal IFN-I scores	Correlation between immune parameters assessed by anti-IFN antibody concentration, the abundance of key immune cell subpopulations, lymphocyte function assessed by functional immune testing (such as IGRA), and the baseline blood and nasal interferon score	One day
To assess the impact of demographic and clinical parameters on baseline blood and nasal IFN-I scores	Correlation between demographic (age, sex) and clinical parameters, and the baseline blood and nasal interferon score	One day
Compare baseline IFN-I levels between two subgroups of participants initially considered uninfected: those in whom the PCR test routinely performed on the day of the visit detects no infection, and those in whom this PCR test reveals an asymptomatic infe	Mean (or median) variation in IFN-I between the two groups, with estimation of the effect size (confidence interval) and the level of statistical significance.	One day
Establishment of a biobank	Establishment of a biobank	One day

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon
• Investigators: Principal Investigator: Sophie TROUILLET-ASSANT, Laboratoire Commun de Recherche, Hôpital Lyon Sud, Hospices Civils de Lyon, France

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2027

Study Registration Dates

• First Submitted: June 15, 2026
• First Submitted That Met QC Criteria: June 18, 2026
• First Posted (Actual): June 24, 2026

Study Record Updates

• Last Update Posted (Actual): June 24, 2026
• Last Update Submitted That Met QC Criteria: June 18, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Healthy volunteers; Reference value; Type I Interferon Response
• Other Study ID Numbers: 69HCL26_0579

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No