Alterations in genes associated with cytosolic RNA sensing in whole blood are associated with coronary microvascular disease in SLE.
Publication Year:
2025
PubMed ID:
39828802
Funding Grants:
Public Summary:
People with systemic lupus erythematosus (SLE)—an autoimmune disease that mostly affects women—are much more likely to die from heart disease than women without lupus. Many SLE patients experience chest pain even when their large heart arteries look normal. This can be due to problems in the tiny blood vessels of the heart, a condition called coronary microvascular disease (CMD), which reduces blood flow and causes heart damage.
In this study, researchers wanted to understand if there are specific gene activity patterns (gene signatures) that distinguish lupus patients who have CMD from those who don’t. They analyzed RNA from blood samples of 11 women with lupus—4 with CMD (confirmed by cardiac MRI) and 7 without—and compared them to healthy individuals.
They found 143 genes that were expressed differently in lupus patients compared to healthy people. Many of these genes were involved in the body’s antiviral defense system and interferon (IFN) signaling, which are already known to be overactive in lupus.
When comparing lupus patients with and without CMD, the researchers found differences in several biological pathways—particularly those related to interferon signaling, RNA sensing, and ADP-ribosylation (a process involved in cell stress and immune responses).
Scientific 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.