W218 - Nasal Transcriptome Changes in Response to Acute Respiratory Viral Infections in Patients with Rheumatoid Arthritis

Abstract Text: Acute respiratory viral infections (ARVI) are the most frequently occurring global illnesses causing significant morbidity and mortality. Adults with rheumatoid arthritis (RA) have increased risk of infection and clinical complications, although the underlying molecular and cellular immune responses remain poorly understood. To address this, we examined transcriptional changes in the upper airway of RA (n=28) and healthy control (HC, n=13) participants during ARVI. We collected nasal swabs at multiple timepoints: Baseline, Days 1-3, Days 4-6, Days 8-11, and 30 days post-symptom onset, and one year post-baseline. Bulk RNA-sequencing was performed followed by differential gene expression analysis using a linear mixed effects model to identify genes with different temporal patterns through acute infection. The majority of participants were infected with SARS-CoV-2 (n=24). Considering airway transcriptomic changes, we observed minimal transcriptional differences between RA and HC patients at Baseline, Days 1-3, and Days 4-6, but there were a greater number of differentially expressed genes over time in RA (n=4102) compared to HC patients (n=324). Next, we built gene modules using Weighted Gene Co-expression Network Analysis (WGCNA) and found that interferon and adaptive immune response modules exhibited a similar pattern of increased expression over time in RA and HC. However, expression of modules enriched in cilium associated pathways and epithelial associated pathways changed exclusively in the RA cohort. Our novel longitudinal study suggests that while there are minimal baseline differences between RA and HC, ARVI induces more temporal transcriptional changes in the upper airway in RA, including alterations in ciliary and epithelial pathways.