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An Immunohistopathologic Study to Profile the Folate Receptor Beta Macrophage and Vascular Immune Microenvironment in Giant Cell Arteritis
Published on: February 8, 2019
Distinct gene signatures of monocytes and B cells in patients with giant cell arteritis: a longitudinal transcriptome
Kotaro Matsumoto1, Katsuya Suzuki2, Hiroto Yoshida3
1Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Tokyo, Shinjuku-ku, Japan. aa615119@keio.jp.
Insights
Giant cell arteritis (GCA) involves monocyte activation and B cell inactivation. Combined treatments improved molecular profiles more than prednisolone alone, offering insights into GCA pathogenesis and treatment response.
Area of Science:
- Immunology
- Genomics
- Vascular Biology
Background:
- Giant cell arteritis (GCA) is a large-vessel vasculitis (LVV) of unknown cause.
- Disease management is challenging due to late symptom onset and frequent relapses.
- Understanding GCA pathophysiology is crucial for improving patient treatment outcomes.
Purpose of the Study:
- To identify molecular signature transitions in immune cells during GCA pathogenesis.
- To analyze longitudinal transcriptome data in GCA patients.
- To correlate molecular changes with treatment response.
Main Methods:
- Whole blood transcriptome analysis of treatment-naive GCA patients, Takayasu arteritis (TAK) patients, and healthy controls (HCs).
- Identification of characteristic GCA genes and longitudinal transition analysis.
- Cell-type identification using CIBERSORT to estimate RNA transcript subsets.
Main Results:
- 739 differentially expressed genes identified among GCA patients and HCs.
- 15 genes characteristically upregulated and 36 downregulated in GCA compared to TAK and HCs.
- GCA showed M0-macrophage upregulation and B cell downregulation, reflecting monocyte activation and B cell inactivation.
Conclusions:
- Monocyte activation and B cell inactivation are key molecular signatures in GCA.
- These gene signatures correlate with treatment response in GCA patients.
- Combined IL-6 receptor antagonist and prednisolone therapy normalized molecular profiles more effectively than monotherapy.
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.
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