BackgroundRheumatoid arthritis (RA) is an inflammatory debilitating disease that affects the joints in the early and productive phases of an individual’s life. Several cytokines have been linked to the disease pathogenesis and are known to contribute to the inflammatory state characteristic of RA. The participation of type I interferon (IFN) in the pathogenesis of the disease has been already described as well as the identity of the genes that are regulated by this molecule, which are collectively known as the type I IFN signature. These genes have several functions associated with apoptosis, transcriptional regulation, protein degradation, Th2 cell induction, B cell proliferation, etc. This article evaluated the expression of several genes of the IFN signature in different stages of disease and their correlation with the levels of anticitrullinated protein antibodies (ACPA) anticarbamylated protein (Anti-CarP) antibodies.MethodsSamples from individuals with early and established RA, high-risk individuals (ACPA+ and ACPA−), and healthy controls were recruited at “Unidad de Artritis y Rheumatismo” (Rheumatism and Arthritis Unit) in Guadalajara Jalisco Mexico. Determinations of ACPA were made with Eurodiagnostica ACPA plus kit. Anti-CarP determinations were made according to previously described protocols. RNA was isolated, and purity and integrity were determined according to RNA integrity number >6. Gene expression analysis was made by RT-qPCR using specific primers for mRNAs of the type I IFN signature. Relative gene expression was calculated according to Livak and Schmitgen.ResultsSignificant differences in gene expression were identified when comparing the different groups for MXA and MXB (P < 0.05), also when comparing established RA and ACPA− in both IFIT 1 and G15. An increased expression of ISG15 was identified (P < 0.05), and a clear tendency toward increase was identified for HERC5. EPSTRI1, IFI6, and IFI35 were found to be elevated in the chronic/established RA and early RA (P < 0.05). Significant correlations were identified for the IFN signature genes with the levels of ACPA and anti-CarP (P < 0.05).ConclusionOur data confirm previous observations in the role of IFN signature and the pathogenesis of RA. Also, we provide evidence of an association between several genes of the IFN signature (that regulate Th2 cells and B cell proliferation) with the levels of anti-CarP antibodies and ACPA.
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
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.