THU0018 Identification of a Specific Transcriptional Profile Associated to Early Rheumatoid Arthritis (RA)

Abstract

BackgroundThe etiopathogenic mechanisms involved in the development of RA are complex and poorly understood. Microarray analysis, as part of the system biology strategies, may be useful to assess molecular mechanisms participating in the initiation of clinically apparent RA.ObjectivesTo assess the transcriptional signatures that may be associated with the transition from preclinical to clinically evident RA.MethodsIn a cross-sectional design, we study 3 groups: a) Anti-CCP positive (ELISA), healthy first-degree relatives of patients with RA (FDR-RA); b) Anti-CCP negative, healthy FDR-RA subjects; c) Patients with early RA (eRA) (<1 year)(ACR/EULAR criteria). RNA labeled samples were obtained from each studied subject and used to assess the transcriptional profiles of each study groups, and hybridized to the Agilent 4x44k microarray chip. Data analyzes were performed using the Gene Spring software to identify the gene expression profiles of each group. Gene ontology and molecular pathways analysis were done as well.Results34 subjects were included (ACCP- (n=12), ACCP+ (n=12), eRA (n=10). A specific transcriptional profile including 876 up-regulated genes and 7531 down-regulated genes in the group of FDR-RA ACCP+ were identified (Figure 1) (some of these genes are known to participate in innate immune response, IFN type 1 response, IFN-γ response, cellular response to chemical and insulin stimulus, etc.). In the eRA group, only 551 genes were up-regulated and 4402 down-regulated genes (the up-regulated genes that participate in the inflammatory and immune response, regulation of metabolic process, cellular response to chemical stimulus, etc.). These two groups were compared with the ACCP negative FDR-RA subjects. Using these strategies of gene ontology (GO), we found 19 genes associated to immune response and inflammation that are up regulated exclusively in eRA patients; it could represent an inflammation signature in eRA patients, and could be used as biomarkers of disease. After GO identification, we analyzed the induced pathways in ACCP+ and eRA. We found pathways with genes that regulate inflammatory genes in ACCP+, and genes that maintain inflammation and proliferation of immune cells in eRA. The identified cascades were shared between RA and ACCP+ subjects, but the up-regulated genes in each cascade were different for each group.ConclusionsCharacteristic transcriptional profiles related to the preclinical autoimmune stage of RA and RA of recent onset were identified. A unique set of nineteen up-regulated genes in eRA can be considered as biomarkers for the early diagnosis of RA. These transcriptional signature associated to eRA suggest a phenomenon of immune tolerance loss in the early stage of the disease.Disclosure of InterestNone declared

Endogenous retroelement activation is implicated in IFN-α production and anti-CCP autoantibody generation in early RA

“…We have previously demonstrated increased IFN-I signaling and serum IFN-α levels in early rheumatoid arthritis (RA) with negative prognostic implications on initial disease control and clinical outcomes (7,8). An elevated interferon gene signature (IGS) also increases the likelihood of progression to RA in at risk populations, such as those with anti-cyclic citrullinated peptide (CCP) positive arthralgia (7)(8)(9)(10)(11)(12)(13). However, it remains unknown what drives this IFN-I release in early RA.…”