Distinct gene signatures of monocytes and B cells in patients with giant cell arteritis: a longitudinal transcriptome analysis

Abstract

Background: Giant cell arteritis (GCA) is a primary large-vessel vasculitis (LVV) of unknown origin. Its management is a challenge due to the late onset of disease symptoms and frequent relapse; therefore, clarifying the pathophysiology of GCA is essential to improving treatment. This study aimed to identify the transition of molecular signatures in immune cells relevant to GCA pathogenesis by analyzing longitudinal transcriptome data in patients. Methods: We analyzed the whole blood transcriptome of treatment-naive patients with GCA, patients with Takayasu arteritis (TAK), age-matched, old healthy controls (HCs), and young HCs. Characteristic genes for GCA were identified, and the longitudinal transition of those genes was analyzed using cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT). Results: Repeated measures analysis of variance revealed 739 differentially expressed genes among all patients and HCs. Of the 739 genes, 15 were characteristically upregulated and 36 were downregulated in patients with GCA compared to those with TAK and HCs. Pathway enrichment analysis showed that downregulated genes in GCA were associated with B cell activation. CIBERSORT analysis revealed that upregulation of “M0-macrophages” and downregulation of B cells were characteristic of GCA. Upregulation of “M0-macrophages” reflects the activation of monocytes in GCA toward M0-like phenotypes, which persisted under 6 weeks of treatment. Combined treatment with prednisolone and an interleukin-6 receptor antagonist normalized molecular profiles more efficiently than prednisolone monotherapy. Conclusions: Gene signatures of monocyte activation and B cell inactivation were characteristic of GCA and associated with treatment response.