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

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

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.

Study Overview

• Status: Unknown
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Diagnostic test: Research new biomarker for RA

• Study Type: Observational
• Enrollment (Anticipated): 200

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The study population will be recruited from rheumatology outpatients

Description

Inclusion Criteria:

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

Exclusion Criteria:

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

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Rheumatoid arthritis; Patients who meet the criteria of the 1987 ACR	Diagnostic test: Research new biomarker for RA; Analyze T and B cell response against new citrullinated peptides
Arthritis not Rheumatoid arthritis; Patients with psoriatic arthritis, peripheric spondyloarthropathies and connective tissue diseases.	Diagnostic test: Research new biomarker for RA; Analyze T and B cell response against new citrullinated peptides
Healthy controls; From health blood donors	Diagnostic test: Research new biomarker for RA; Analyze T and B cell response against new citrullinated peptides

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
T cell response	Proliferation against new citrullinated peptides	2 years
B cell response	Detection antibodies against new citrullinated peptides	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HLA-DRB1	Typing HLA-DRB1	2 years
Rheumatic factor	Turbidimetric assay	2 years
Anti-Citrullinated Peptides Antibodies	ELISA assay	2 years

Collaborators and Investigators

• Sponsor: Corporacion Parc Tauli

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): September 1, 2018
• Primary Completion (ANTICIPATED): September 1, 2019
• Study Completion (ANTICIPATED): September 1, 2020

Study Registration Dates

• First Submitted: April 13, 2018
• First Submitted That Met QC Criteria: April 20, 2018
• First Posted (ACTUAL): April 23, 2018

Study Record Updates

• Last Update Posted (ACTUAL): April 23, 2018
• Last Update Submitted That Met QC Criteria: April 20, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: Autoantibodies; Shared epitope; HLA-DRB1; Citrullinated peptides
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid
• Other Study ID Numbers: CIR2017/011

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No