Inflammatory autoimmune diseases, often influenced by both genetic and environmental factors, share many features. Of more than 80 clinically distinct autoimmune conditions, three diseases — rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Sjögren’s syndrome (SjS)–share a signature gene expression pattern. A recent publication from a collaboration between Spanish researchers and a laboratory in Oklahoma Medical Research Foundation discussed overlapping biological processes among the three diseases that result from similar gene expression.
“Shared Signatures Between Rheumatoid Arthritis, Systemic Lupus Erythematosus, and Sjögren’s Syndrome Uncovered Through Gene Expression Meta-Analysis,” published in Arthritis Research & Therapy, was motivated by the similarities in the course of disease and treatment for the three disorders. The team wanted to learn more about the molecular mechanisms behind the diseases and looked to gene expression, which can be conducted readily through high-throughput technologies that include microarrays and next generation sequencing.
To begin, the researchers obtained gene expression datasets from the Gene Expression Omnibus database. Careful statistical analysis, modeling, and functional analysis revealed similarities among the diseases.
Over 370 genes were differentially expressed by patients with RA, SLE, and SjS when compared to healthy individuals: 187 were under-expressed and 184 were over-expressed. Most genes were previously explored as biomarkers for the individual diseases, but some were indicators of a shared pathological state.
Over-expressed genes common to all diseases were genes involved in immune and inflammatory responses, cell division, cytokine-mediated signaling pathways, cell death, and viral responses. Those genes that were under-expressed were related to inhibited protein synthesis.
“Although there are previous gene expression meta-analyses of immune related diseases, this is the first one that integrates data from these three specific disorders, allowing us to define common biological processes,” wrote the authors. The team believes future analysis and functional studies will provide greater insight in the pathogenesis of systemic autoimmune conditions similar to RA.