Study of the Articular Microbiota in Rheumatoid Arthritis. (MICROPORE)

The cause of rheumatoid arthritis (RA) remains unknown, although major advances have been done these last ten years in the comprehension of its pathophysiology.

The aim of this study is to described a synovial microbiota specific for rheumatoid arthritis.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis; Arthrosis; Synovial Disorder
• Intervention / Treatment: Procedure: Joint puncture

Detailed Description

The cause of rheumatoid arthritis (RA) remains unknown, although major advances have been done these last ten years in the comprehension of its pathophysiology. One of the most significant discoveries was the post-translational modification of various self-proteins resulting in the replacement of arginine residues by citrulline. This conversion results in modifications of the basic charge of the peptides, of its primary and secondary structure, and the transformed peptides can then bound to some HLA-DR molecules (HLA-DR4, HLA-DR1), that are the best well known genetic factors of rheumatoid arthritis (RA). This leads to immunization to citrullinated peptides in genetically predisposed patients, which is now identified as the most characteristic auto-immun phenomenon of RA. Anti-citrullinated peptide antibodies (ACPA) have become the most relevant biologic test for the diagnosis of RA.

The conversion to citrulline is due to the action of an enzyme, the peptidyl arginine deiminase (PAD). Endogenous PADs have been identified in humans, but their activation needs high concentrations of calcium in the cells that are not physiological. Thus, the activation of self-PADs occurs only in extreme conditions, such as apoptosis, or major stresses resulting from toxic or infectious process. But some bacteria also contain PADs that are involved in their energetic metabolism. Two main factors have yet been identified to lead to citrullination of self-peptides and are now recognized as important environment risk factors for RA: smoking and periodontitis. Periodontitis is the consequence of an infection that is mainly due to Porphyromonas gingivalis, one of the bacteria processing a PAD. These facts reinforce the old hypothesis of an infectious origin of RA.

However, all RA patients are neither smoker nor affected by periodontitis, and many other bacteria have PADs and may be involved in the pathophysiology of RA. Moreover, it has been demonstrated that citrullination process and ACPA production can precede RA for years, while the citrullination and ACPA production are located to a mucous membrane (oral, pulmonary…). How these processes reach the joint remains a mystery.

The hypothesis is that the involved bacteria translocate to the joint, inducing local citrullination of synovial peptides, inflammation and production of ACPA within the joint, and resulting in arthritis.

The aim of this study is to demonstrate this translocation of bacteria in the synovium, and to described a synovial microbiota specific for rheumatoid arthritis .

Pilot study, including only few patients, just to demonstrate the validity of the translocation concept and the performance of the procedures.

• Study Type: Observational
• Enrollment (Actual): 36

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

This is a pilot study. The number of subjets will be 12 RA patients and 6 controls suffering from osteoarthritis.

Description

Inclusion Criteria:

• patients presenting with RA according to ACR87 and ACR/EULAR 2010 criteria
• patients presenting with RA anti-citrullinated peptide antibodies positive
• patients presenting with active RA, characterized by at least one synovitis
• patients presenting with an arthritis requiring arthrocentesis and synovial fluid collection for diagnostic or therapeutic purpose
• patients giving agreement to participate to the study and to sign informed consent.

Exclusion Criteria:

• patients suffering from osteoarthritis
• patients presenting with joint effusion justifying an arthrocentesis and synovial fluid collection for diagnostic of therapeutic purpose
• patients giving agreement to participate to the study and to sign informed consent
• Patients presenting with another arthropathy than anti-citrullinated peptide antibodies positive RA or osteoarthritis
• Patients not requiring arthrocentesis for medical reasons
• Patients refusing to sign informed consent
• Patients presenting with understanding problems due to language or cognitive reasons.

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Rheumatoid arthritis group; Patients with rheumatoid arthritis	Procedure: Joint puncture; Patient requiring joint puncture for diagnostic or therapeutic reasons.
Control group; Patients with osteoarthritis / joint effusion.	Procedure: Joint puncture; Patient requiring joint puncture for diagnostic or therapeutic reasons.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Presence of bacterial DNA by 16s PCR	Detection by 16s PCR of DNA of bacterial origin in synovial fluid specimens	At the screening
Presence of a characteristic microbiota	Research of a characteristic microbiota of rheumatoid arthritis	At the screening

Collaborators and Investigators

• Sponsor: University Hospital, Bordeaux
• Investigators: Principal Investigator: Emilie SHIPLEY, Dr, University Hospital, Bordeaux

Study record dates

Study Major Dates

• Study Start (Actual): February 21, 2012
• Primary Completion (Actual): February 22, 2013
• Study Completion (Actual): February 22, 2013

Study Registration Dates

• First Submitted: August 12, 2019
• First Submitted That Met QC Criteria: August 13, 2019
• First Posted (Actual): August 14, 2019

Study Record Updates

• Last Update Posted (Actual): August 14, 2019
• Last Update Submitted That Met QC Criteria: August 13, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: Translocation; Synovial microbiota
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Osteoarthritis
• Other Study ID Numbers: CHU BX 2011/12

Plan for Individual participant data (IPD)

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