Clinical trial NCT03506035: Alloimmune Response to Citrullinated Shared Epitope Sequence in Patients With Rheumatoid Arthritis
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
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Rheumatoid Arthritis
Keywords: Shared epitope
HLA-DRB1
Citrullinated peptides
Autoantibodies
Lead sponsor: Corporacion Parc Tauli
Sponsor class: OTHER
First posted: 2018-04-23
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study population will be recruited from rheumatology outpatients

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.


Eligibility criteria: 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

Primary outcomes:
measure: T cell response
timeFrame: 2 years
measure: B cell response
timeFrame: 2 years
Secondary outcomes:
measure: HLA-DRB1
timeFrame: 2 years
measure: Rheumatic factor
timeFrame: 2 years
measure: Anti-Citrullinated Peptides Antibodies
timeFrame: 2 years
Other outcomes:
Locations:
Study officials:
References: