Identification of Genomic Biomarkers for Rheumatoid Arthritis With Late Onset (BIOGENOPRAT)

Rheumatoid arthritis (RA) is a disabling disease leading to joint and bones destruction. This autoimmune disease is multifactorial, and some genetic and environmental risk factors are already described. However, a part of heritability is still unknown. Previous genomics studies dedicated to deciphering this missing heritability did not pay attention to age of onset. The purpose of this protocol is to determine genomic markers which are specific of RA with an age of onset above 65 years old. Indeed, clinical presentation, treatment tolerance and efficiency, and frequent comorbidities of this phenotype are particular. This signature of genomic biomarkers will be integrated in known molecular pathways to highlight specificities, helpful for biological targets identification.

Study Overview

• Status: Withdrawn
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Other: Salivary sampling

Detailed Description

The purpose of this protocol is to identify a genomic signature specific of late onset RA and to contribute to the characterization of dedicated therapeutic targets. Collection of patients will be held at the rheumatology service of CHSF (Corbeil-Essonnes, France) and salivary samples will be collected for further genomic analyses conducted by GenHotel lab (Univ Evry - Univ Paris-Saclay, Evry, France).

First, analysis of whole genome/DNA sequences will allow to identify specific variants of late onset RA. Such identified biomarkers would help differential diagnosis and contribute to earlier initiation of care for RA relatives at risk of developing RA. Second, analysis of RNA sequences, including coding protein genes and non-coding RNA, will give information about gene expression and regulation, and molecular pathways. Comparison of patient groups will allow discrimination of biomarkers and molecular signature specific to the disease and to its onset phenotypes. Integration of such genomic data in the RA disease map (consisted of a network of biological pathways), and further modeling approaches, will highlight late onset RA particularities on which research of therapeutic target could be focused on.

To complete genomic analysis, methylome and proteome data will be produced in a second phase. Such data will help in identification of regulation process leading to a protein profile specific of late onset RA.

An ancillary study is planned from familial samples identified after analysis of data collected from RA patients. Risk genetic markers identification is facilitated in a familial context of analyses. Furthermore, non RA individuals in familial sample provide a control sample allowing better discrimination between family-dependent and phenotype-dependent genomic markers

• Study Type: Observational

Contacts and Locations

Study Locations

• France
  • Corbeil-Essonnes, France, 91106
    • Centre Hospitalier Sud Francilien

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Patients followed by the rheumatology service of CHSF

Description

Inclusion Criteria:

• patient with RA diagnosed before 60 years (PRp group)
• patient with RA diagnosed from 65 years (PRt group)
• patient without RA followed for osteoarthritis matched with patient of PRt according to age (+/- 1 year) and sex (Tem group).
• relative of patient PRt, without RA or with RA, regardless of age of onset (Ap group)
• patient who agreed to participate in the study and signed an informed consent

Exclusion Criteria:

• other inflammatory and/or autoimmune known disease for patients of PRp and PRt groups
• first symptoms of osteoarthritis before 40 years, other known inflammatory disease, other known autoimmune disease for Tem group.

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
PRp; Patients with a diagnostic of rheumatoid arthritis with an age of onset before 60 years	Other: Salivary sampling; Salivary sampling for genomic material (DNA and RNA (for primary outcome measures); proteins and DNA methylation (for secondary outcome measures)
PRt; Patients with a diagnostic of rheumatoid arthritis with an age of onset from 65 years	Other: Salivary sampling; Salivary sampling for genomic material (DNA and RNA (for primary outcome measures); proteins and DNA methylation (for secondary outcome measures)
Tem; Patients with a diagnostic of osteoarthritis without RA	Other: Salivary sampling; Salivary sampling for genomic material (DNA and RNA (for primary outcome measures); proteins and DNA methylation (for secondary outcome measures)
Ap; Relatives to PRt, with RA (with any age of onset) or without RA	Other: Salivary sampling; Salivary sampling for genomic material (DNA and RNA (for primary outcome measures); proteins and DNA methylation (for secondary outcome measures)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Genomic signature for late onset rheumatoid arthritis	Genomic DNA analysis	at day 0
Gene expression for late onset rheumatoid arthritis	RNA analysis	at day 0

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Methylome for late onset rheumatoid arthritis	DNA methylation profile	at day 0
Proteome for late onset rheumatoid arthritis	Protein profile	at day 0

Collaborators and Investigators

• Sponsor: Centre Hospitalier Sud Francilien
• Investigators: Study Director: Elisabeth PETIT-TEIXEIRA, Laboratoire GenHotel Université d'Evry Val d'Essonne

Study record dates

Study Major Dates

• Study Start (Estimated): May 28, 2025
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2028

Study Registration Dates

• First Submitted: March 29, 2023
• First Submitted That Met QC Criteria: March 29, 2023
• First Posted (Actual): April 11, 2023

Study Record Updates

• Last Update Posted (Actual): August 17, 2025
• Last Update Submitted That Met QC Criteria: August 13, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: RNAseq; Proteome; Genomic biomarkers; Methylome; Late onset rheumatoid arthritis; Whole genome sequences
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Joint Diseases; Rheumatic Diseases; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Arthritis; Arthritis, Rheumatoid
• Other Study ID Numbers: 2022/0023

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No