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

Background The 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. Objectives To assess the transcriptional signatures that may be associated with the transition from preclinical to clinically evident RA. Methods In 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) ( Results 34 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. Conclusions Characteristic 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 Interest None declared