Identification of Genomic Biomarkers for Rheumatoid Arthritis With Late Onset

Study Overview
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Brief Summary
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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.

Detailed Description
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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

Official Title
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Identification of Genomic Biomarkers for Rheumatoid Arthritis With Late Onset

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Other: Salivary sampling


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Late onset rheumatoid arthritis, Genomic biomarkers, Whole genome sequences, RNAseq, Proteome, Methylome