Alterations in genes associated with cytosolic RNA sensing in whole blood are associated with coronary microvascular disease in SLE

• DOI: 10.1101/2024.02.19.580713
• Publication Date: 2024-02-27T18:11:17Z
• Authors: Lihong Huo; Erica Montano; Gantseg Tumurkhuu; Moumita Bose; Daniel S. Berman; Daniel Wallace; Janet Wei; Mariko Ishimori; C. Noel Bairey Merz; Caroline Jefferies
• Keywords: Systemic lupus erythematosus; Coronary microvascular disease; Science; Q; R; Interferon; Medicine; Gene expression; Article

Abstract Objective To investigate whether gene signatures discriminate systemic lupus erythematosus (SLE) patients with coronary microvascular dysfunction (CMD) from those without and any signaling pathway is linked to the underlying pathobiology of SLE CMD. Methods This study collected whole blood RNA samples female subjects aged 37 57, comprising 11 (4 SLE-CMD, 7 SLE-non-CMD) 10 HC. Total was then used for library preparation sequencing. Differential expression analysis performed identify associated CMD in using DEseq2 v1.42.0. Gene Set Enrichment Analysis were by ClusterProfiler v4.10.0 pathfindR v2.3.1. Results RNA-seq revealed 143 differentially expressed (DE) genes between HC groups. GO indicated associations virus defense interferon SLE. 14 DE identified comparison SLE-CMD SLE-non-CMD adjusted parameters (padj < 0.1). Notably, exhibited elevated levels sensing, while downregulated coagulation cell-cell junction. Further investigation highlighted differences IFN ADP-ribosylation pathways SLE-non-CMD, suggesting distinct molecular mechanisms vascular changes reduced left ventricular function non-CMD. Conclusion Our a unique signature compared group, highlighting significant involvement type 1 interferon, RIG-I family proteins, chronic inflammation progression SLE-CMD. The intricate relationship these factors underscores their probable role initiating advancing