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

Daniel Toro-Domínguez, Pedro Carmona-Sáez, Marta E Alarcón-Riquelme

IntroductionSystemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and Sjögren¿s syndrome (SjS) are inflammatory and systemic autoimmune diseases (SADs) that share several clinical and pathological features. The shared biological mechanisms are not fully characterized. The objective of this study was to perform a meta-analysis using publicly available gene expression data from the three diseases in order to identify shared gene expression signatures and overlapping biological processes.MethodsPreviously reported gene expression datasets were selected and downloaded from Gene Expression Omnibus (GEO) database. Normalization and initial preprocessing was performed using statistical programming language R and random effect model (REM) based meta-analysis was carried out using the INMEX software. Functional analysis of over- and under-expressed genes was done using the GeneCodis tool.ResultsThe gene expression meta-analysis revealed a SAD signature composed of 371 differentially expressed genes in patients and healthy controls, 187 under-expressed and 184 over-expressed. Many of these genes have been previously reported as significant biomarkers for individual diseases, but others provide new clues to understand the shared pathological state. Functional analysis showed that over-expressed genes were mainly involved in immune and inflammatory response, mitotic cell cycle, cytokine-mediated signaling pathways, apoptotic processes, type I interferon (IFN)-mediated signaling pathway and response to virus. On the other hand, under-expressed genes were primarily involved in inhibition of protein synthesis.ConclusionsWe define a common gene expression signature for SLE, RA and SjS. The analysis of this signature revealed relevant biological processes that may be playing important roles in the shared development of these pathologies.