Interleukin‐1 pathway in active large vessel vasculitis patients with a poor prognosis: a longitudinal transcriptome analysis

Abstract

Abstract Objectives Large vessel vasculitis (LVV) is characterised by a high relapse rate. Because accurate assessment of the LVV disease status can be difficult, an accurate prognostic marker for initial risk stratification is required. We conducted a comprehensive longitudinal investigation of next‐generation RNA‐sequencing data for patients with LVV to explore useful biomarkers associated with clinical characteristics. Methods Key molecular pathways relevant to LVV pathogenesis were identified by examining the whole blood RNA from patients with LVV and healthy controls (HCs). The data were examined by pathway analysis and weighted gene correlation network analysis (WGCNA) to identify functional gene sets that were differentially expressed between LVV patients and HCs, and associated with clinical features. We then compared the expression of the selected genes during week 0, week 6, remission and relapse. Results The whole‐transcriptome gene expression data for 108 samples obtained from LVV patients (n = 27) and HCs (n = 12) were compared. The pathway analysis and WGCNA revealed that molecular pathway related to interleukin (IL)‐1 was significantly upregulated in LVV patients compared with HCs, which correlated with the positron emission tomography vascular activity score, a disease‐extent score based on the distribution of affected arteries. Further analysis revealed that the expression levels of genes in the IL‐1 signalling pathway remained high after conventional treatment and were associated with disease relapse. Conclusion Upregulation of the IL‐1 signalling pathway was a characteristic of LVV patients and was associated with the extent of disease and a poor prognosis.

Keywords

• gene expression
• giant cell arteritis
• interleukin‐1
• large vessel vasculitis
• Takayasu's arteritis