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

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.

Single-Cell RNA Sequencing Revealed CD14+ Monocytes Increased in Patients With Takayasu’s Arteritis Requiring Surgical Management

“…However, it remains unclear how the other types of inflammatory cells in the peripheral blood contribute to the progression and development of TA. Kotaro found that IL-1 pathway expression was elevated in the peripheral blood of patients with refractory large vessel vasculitis by analyzing bulk-seq data, but the author failed to elucidate the relationship between the IL-1 pathway and different types of immune cells ( Matsumoto et al, 2021 ). Compared with bulk-seq, scRNA-seq technology can analyze the transcriptome in each cell type, which provides more comprehensive information on the function of different inflammatory cells.…”

Transcriptome profiling of abdominal aortic tissues reveals alterations in mRNAs of Takayasu arteritis

“…To the best of our knowledge, this study firstly performed bulk RNA-sequencing of TA vessel tissues to obtain the overall alterations of transcriptome in TA. Regarding the materials used for TA research, most studies detected RNA, cytokines, chemokines by using peripheral blood samples ( Matsumoto et al, 2021 ; Qing et al, 2021 ; Kabeerdoss et al, 2022 ; Kong et al, 2022 ). In this way, several susceptibility locus have been identified by genome-wide association studies to pinpoint potential clues for new therapeutic targets ( Renauer et al, 2015 ; Ortiz-Fernández et al, 2021 ).…”

“…The results of IL1R1 and IL1R2 IHC staining confirmed these bioinformatic analysis. Examined the whole blood RNA and draw a conclusion that IL-1 signaling pathway related to the advanced stage of disease and a poor prognosis ( Matsumoto et al, 2021 ). IL-1 and IL1R may be a potential target of TA treatment, in which further studies are required.…”

The neutrophil: A key resourceful agent in immune‐mediated vasculitis

“…However, it is unclear whether this would affect neutrophil function. 321 The soluble pattern recognition 1 receptor pentraxin 3, which is involved in vascular injury, is upregulated in GCA as in other types of vasculitis. 322 Taken together, these results provide proof of concept that neutrophils may participate in the pathogenesis of GCA.…”

“…Whether this affects neutrophil function remains to be elucidated. 321 Interestingly, anti-endothelial cell antibodies have been reported in TAK, although their role in pathophysiology remains unclear. 343,344 The major histological difference observed on the vascular wall in TAK compared to GCA is the thickening of the adventitia.…”