Alloimmune Response to Citrullinated Shared Epitope Sequence in Patients With Rheumatoid Arthritis

NCT03506035 | Unknown DMC

• 1 other identifier: CIR2017/011
• Study Type: observational
• Target: 200
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Rheumatoid Arthritis

Keywords

Shared epitope; HLA-DRB1; Citrullinated peptides; Autoantibodies

Outcome Measures

Primary Outcomes (2)

• T cell response

  Proliferation against new citrullinated peptides

  2 years

• B cell response

  Detection antibodies against new citrullinated peptides

  2 years

Secondary Outcomes (3)

• HLA-DRB1

  2 years

• Rheumatic factor

  2 years

• Anti-Citrullinated Peptides Antibodies

  2 years

Study Arms (3)

Rheumatoid arthritis

Patients who meet the criteria of the 1987 ACR

Diagnostic Test: Research new biomarker for RA

Arthritis not Rheumatoid arthritis

Patients with psoriatic arthritis, peripheric spondyloarthropathies and connective tissue diseases.

Diagnostic Test: Research new biomarker for RA

Healthy controls

From health blood donors

Diagnostic Test: Research new biomarker for RA

Interventions

Research new biomarker for RA DIAGNOSTIC_TEST

Analyze T and B cell response against new citrullinated peptides

Arthritis not Rheumatoid arthritis; Healthy controls; Rheumatoid arthritis

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study population will be recruited from rheumatology outpatients

You may qualify if:

• Patients with RA who meet 1987 ACR criteria Patients with arthritis no RA

You may not qualify if:

• Having an intellectual disability that allows understanding the informed consent to participate in the study

Sponsors & Collaborators

• Corporacion Parc Tauli: lead

MeSH Terms

Conditions

Arthritis, Rheumatoid

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Central Study Contacts

Eduard Graell, MD. PhD

CONTACT

+34 937231010; egraell@tauli.cat

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD. PhD

Study Record Dates

• First Submitted: April 13, 2018
• First Posted: April 23, 2018
• Study Start: September 1, 2018
• Primary Completion: September 1, 2019
• Study Completion: September 1, 2020
• Last Updated: April 23, 2018

Record last verified: 2018-04