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

## TL;DR

This study finds that gene changes related to RNA sensing in blood are linked to coronary microvascular disease in women with lupus.

## Contribution

The first study to identify gene signatures associated with coronary microvascular disease in systemic lupus erythematosus.

## Key findings

- 143 genes were differentially expressed in SLE compared to healthy controls, involving virus defense and interferon signaling.
- SLE patients with CMD showed distinct gene expression patterns in RNA sensing and ADP-ribosylation pathways.
- CMD in SLE appears to involve unique molecular mechanisms compared to non-CMD cases.

## Abstract

Systemic lupus erythematosus (SLE) patients are 90% women and over three times more likely to die of cardiovascular disease than women in the general population. Chest pain with no obstructive cardiac disease is associated with coronary microvascular disease (CMD), where narrowing of the small blood vessels can lead to ischemia, and frequently reported by SLE patients. Using whole blood RNA samples, we asked whether gene signatures discriminate SLE patients with coronary microvascular dysfunction (CMD) on cardiac MRI (n=4) from those without (n=7) and whether any signaling pathway is linked to the underlying pathobiology of SLE CMD. RNA-seq analysis revealed 143 differentially expressed (DE) genes between the SLE and healthy control (HC) groups, with virus defense and interferon (IFN) signaling being the key pathways identified as enriched in SLE as expected. We next conducted a comparative analysis of genes differentially expressed in SLE-CMD and SLE-non-CMD relative to HC samples. Our analysis highlighted differences in IFN signaling, RNA sensing and ADP-ribosylation pathways between SLE-CMD and SLE-non-CMD. This is the first study to investigate possible gene signatures associating with CMD in SLE, and our data strongly suggests that distinct molecular mechanisms underly vascular changes in CMD and non-CMD involvement in SLE.