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

Rheumatoid Arthritis Clinical Trial

— ABSEC  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03506035
• Other study ID #: CIR2017/011
• Status: Not yet recruiting
• First received: April 13, 2018
• Last updated: April 20, 2018
• Start date: September 1, 2018
• Est. completion date: September 1, 2020

Study information

• Verified date: April 2018
• Source: Corporacion Parc Tauli
• Contact: Eduard Graell, MD. PhD
• Phone: +34 937231010
• Email: egraell[@]tauli.cat
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 200
• Est. completion date: September 1, 2020
• Est. primary completion date: September 1, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Diagnostic Test:
• Research new biomarker for RA
Analyze T and B cell response against new citrullinated peptides

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Corporacion Parc Tauli

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	T cell response	Proliferation against new citrullinated peptides	2 years
Primary	B cell response	Detection antibodies against new citrullinated peptides	2 years
Secondary	HLA-DRB1	Typing HLA-DRB1	2 years
Secondary	Rheumatic factor	Turbidimetric assay	2 years
Secondary	Anti-Citrullinated Peptides Antibodies	ELISA assay	2 years