Shared signatures between rheumatoid arthritis, systemic lupus erythematosus and Sjögren's syndrome uncovered through gene expression meta-analysis

Abstract

Introduction: Systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and Sjögren's syndrome (SjS) are inflammatory systemic autoimmune diseases (SADs) that share several clinical and pathological features. The shared biological mechanisms are not yet fully characterized. The objective of this study was to perform a meta-analysis using publicly available gene expression data about the three diseases to identify shared gene expression signatures and overlapping biological processes. Methods: Previously reported gene expression datasets were selected and downloaded from the Gene Expression Omnibus database. Normalization and initial preprocessing were performed using the statistical programming language R and random effects model-based meta-analysis was carried out using INMEX software. Functional analysis of over- and underexpressed genes was done using the GeneCodis tool. Results: The gene expression meta-analysis revealed a SAD signature composed of 371 differentially expressed genes in patients and healthy controls, 187 of which were underexpressed and 184 overexpressed. Many of these genes have previously been reported as significant biomarkers for individual diseases, but others provide new clues to the shared pathological state. Functional analysis showed that overexpressed genes were involved mainly in immune and inflammatory responses, mitotic cell cycles, cytokine-mediated signaling pathways, apoptotic processes, type I interferon-mediated signaling pathways and responses to viruses. Underexpressed genes were involved primarily in inhibition of protein synthesis. Conclusions: We define a common gene expression signature for SLE, RA and SjS. The analysis of this signature revealed relevant biological processes that may play important roles in the shared development of these pathologies.