Alloimmune Response to Citrullinated Shared Epitope Sequence in Patients With Rheumatoid Arthritis
- Conditions
- Rheumatoid Arthritis
- Interventions
- Diagnostic Test: Research new biomarker for RA
- Registration Number
- NCT03506035
- Lead Sponsor
- Corporacion Parc Tauli
- Brief Summary
Rheumatoid arthritis (RA) is an autoimmune and sistemic disease,characterized by joint sinovitis and the production of autoantibodies (Ab). The Ab against citrullinated peptides (ACPA) are the most specific (92-98%), and high sensitivity (75-81%) and they are of prognostic value. ACPA are already in the beginning of the disease in most cases, having been found years before its onset. Recent studies have suggested that ACPA may have a role in perpetuating inflammation, in the generation of bone erosions and in pain in RA.
Citrullination is a post-translational modification mediated by the PAD, which transforms an arginine into a citrulline. In vivo, this enzyme acts in proinflammatory environments. Despite being widely studied, none of the natural citrullinated substrates have been shown to be the triggering and/or perpetuating factor in the response of B cells in RA, understanding this response as the production of ACPA. In fact, the most specific and sensitive commercial test for the detection of ACPA uses synthetic peptides protected by a patent.
In the other hand, the genetic factor that most increases susceptibility to develop RA is a shared sequence of aminoacids (QKRAA, QRRAA i RRRAA), in the HLA-DRB1 gene, known as the shared epitope (SE). Also, SE, confers prognostic value, and is associated with the presence of ACPA. These SE sequences contain arginines (R), which are susceptible to be citrullinated by the PAD enzyme.
We propose the hypothesis that citrullinated SE act as an antigen capable of activating the inflammatory response mediated by B and T cells in RA. The recognition of an HLA as a foreign one, would originate an answer of alloimmune type, not valued to date.
The objective of the study is to test the immune response mediated by B cells and T cells, in cases and control samples, through an in vitro model that confronts them with peptides containing the citrullinated-SE sequence. In addition, we will evaluate the association between these results with the clinical features of cases (RA included in the study). Their role as a biomarker, as well as their potential to improve the tests currently available to detect ACPA will be explored.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 200
- Patients with RA who meet 1987 ACR criteria Patients with arthritis no RA
- Having an intellectual disability that allows understanding the informed consent to participate in the study
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Rheumatoid arthritis Research new biomarker for RA Patients who meet the criteria of the 1987 ACR Healthy controls Research new biomarker for RA From health blood donors Arthritis not Rheumatoid arthritis Research new biomarker for RA Patients with psoriatic arthritis, peripheric spondyloarthropathies and connective tissue diseases.
- Primary Outcome Measures
Name Time Method B cell response 2 years Detection antibodies against new citrullinated peptides
T cell response 2 years Proliferation against new citrullinated peptides
- Secondary Outcome Measures
Name Time Method HLA-DRB1 2 years Typing HLA-DRB1
Rheumatic factor 2 years Turbidimetric assay
Anti-Citrullinated Peptides Antibodies 2 years ELISA assay