Rheumatoid Arthritis
Conditions
Keywords
Rheumatoid arthritis, Interstitial lung disease, Autotaxin, Lysophosphatidic acid
Brief summary
Rheumatoid arthritis (RA) is a common chronic systemic autoimmune relapsing disease characterized by joint inflammation. Beside arthritis leading to progressive joint damage and loss of function, RA is also associated to extraarticular inflammatory conditions such as interstitial lung disease (ILD). This one develops in 30% of all RA patients with a median survival expectancy of 3 to 10 years once symptomatic. Unfortunately, there is no medical care recommendation so far as the pathophysiology is unknown. However, ILD share many similarities with idiopathic pulmonary fibrosis (IPF). Autotaxin (ATX), due to its lysophospholipase activity, produces a bioactive lipid, lysophosphatidic acid (LPA) under inflammation. LPA has pleiotropic actions inducing cell proliferation, survival, motility and differentiation. Increased ATX and LPA levels have been detected in synovial fluid of RA patients and in IPF patients. ATX is also currently the target for a phase 3 clinical trial in IPF. Given the previous described role of ATX/LPA axis in arthritis and inflammation-induced bone loss in RA and the similarities between RA-ILD and IPF, the investigators hypothesized that ATX/LPA axis may be also an attractive drug target for this pulmonary condition in RA and therefore that ATX and LPA may be increased in sputum from RA patients with ILD in comparison with sputum from RA patients without ILD.
Interventions
OTHERQuantitative ATX and LPA determination in plasma and sputum
Determination of ATX and LPA levels in plasma and sputum from RA-ILD patients (cases) and in plasma and sputum from RA patients without ILD (controls) after sputum induction using hypertonic saline inhalation
Sponsors
Hospices Civils de Lyon
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
General inclusion criteria * Subject aged ≥ 18 and ≤ 70 years * Patient with RA with ACPA in the state phase, meeting ACR / EULAR 2010 criteria * For female subjects: * Likely to procreate: negative pregnancy test at the inclusion visit and use of an effective method of contraception (hormonal contraceptives, intrauterine devices, vasectomized partner, abstinence) started at least 1 month before inclusion and continued during the entire study. * Inability to procreate: menopause (absence of a rule for at least 1 year) or hysterectomy or bilateral oophorectomy or tubal ligation. * Subject having given written consent to participate in the study * Subject affiliated to the Social Security scheme or benefiting from an equivalent scheme Additional inclusion criteria for cases (RA patients with PID): \- PID is defined as damage compatible with the thoracic scanner in thin sections according to international criteria with or without associated clinical signs. Additional inclusion criteria for control patients (RA patients without symptomatology without PID) \- No functional lung complaints
Exclusion criteria
General
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ATX and LPA levels in sputum from RA patients with ILD in comparison with sputum from RA patients without ILD | Month 30 | All the samples will be frozen and ATX and LPA levels will be assessed in the plasma and sputum at the same time, at the end of the recruitment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Correlation between ATX and LPA levels and severity of RA-ILD estimated by tomodensitometry | Month 24 | Determine the correlation between ATX and LPA levels and the severity of CT scan pulmonary involvement\*. \*Diffuse interstitial lung disease is defined as an attack compatible with the thoracic scanner in thin sections according to international criteria with or without associated clinical signs. |
Countries
France
Contacts
Primary ContactFabienne COURY-LUCAS, MD
Outcome results
None listed