Longitudinal monitoring of circulating immune cell phenotypes in large vessel vasculitis

Matsumoto, Kotaro; Suzuki, Katsuya; Yoshida, Hiroto; Magi, Mayu; Kaneko, Yuko; Takeuchi, Tsutomu

doi:10.1016/j.autrev.2022.103160

Cited by 4 publications

(5 citation statements)

References 117 publications

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“…In addition, TCZ reverses the glycolysis and calcium signaling abnormalities observed in Treg dysfunction in patients with GCA (8). However, it is important to note that TCZ has less effect on the proportion of Th1 and CD8 T cells in the circulation, and that Th1and CD8-mediated inflammation may persist under TCZ treatment, particularly in TAK (10,11). Th1-and CD8-mediated interferon (IFN)-g responses are observed in TAK rather than in GCA (2)(3)(4)(5).…”

Section: Il-6 Receptor Antagonistmentioning

confidence: 99%

“…• Improved the imbalanced proportions of Th17, Tfh, and Treg (10,11) • Less effect on the proportion of Th1 and CD8 (10,11) TNF-a receptor antagonist…”

Section: Il-6 Receptor Antagonistmentioning

confidence: 99%

“…Giant cell arteritis (GCA) and Takayasu arteritis (TAK) are two types of primary largevessel vasculitis (LVV) characterized by a predominantly granulomatous infiltration of T cells, macrophages, and multinucleated giant cells (1). The pathophysiology of LVV is not sufficiently elucidated; however, the involvement of Th1 and Th17 immune-mediated responses and an imbalance between Th17 and regulatory T (Treg) cells have been demonstrated in LVV (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12). Glucocorticoids (GC) are used as a standard treatment for LVV and are effective in inducing remission.…”

Section: Introductionmentioning

confidence: 99%

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Changes in the molecular profiles of large-vessel vasculitis treated with biological disease-modifying anti-rheumatic drugs and Janus kinase inhibitors

et al. 2023

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Giant cell arteritis and Takayasu arteritis are two types of primary large-vessel vasculitis (LVV). Although glucocorticoids (GC) are the standard treatment for LVV, the disease relapse rates are high. Recent clinical trials on biological disease-modifying anti-rheumatic drugs (bDMARDs) and Janus kinase (JAK) inhibitors have demonstrated their efficacy in reducing LVV relapse rates and GC dosages. However, the control of residual inflammation and degenerative alterations in the vessel wall remains an outstanding requirement in the clinical management of LVV. The analysis of immune cell phenotypes in patients with LVV may predict their response to treatment with bDMARDs and JAK inhibitors and guide their optimal use. In this mini-review, we focused on molecular markers, including the immune cell proportions and gene expression, in patients with LVV and in mouse models of LVV treated with bDMARDs and JAK inhibitors.

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Section: Il-6 Receptor Antagonistmentioning

confidence: 99%

“…• Improved the imbalanced proportions of Th17, Tfh, and Treg (10,11) • Less effect on the proportion of Th1 and CD8 (10,11) TNF-a receptor antagonist…”

Section: Il-6 Receptor Antagonistmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Changes in the molecular profiles of large-vessel vasculitis treated with biological disease-modifying anti-rheumatic drugs and Janus kinase inhibitors

et al. 2023

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“…However, Th1 and Th17 immune-mediated responses and an imbalance between Th17 and regulatory T (Treg) cells were previously shown in LVV. IFN-γ and IL-17 derived from Th1 and Th17 cells are the dominant cytokines (5)(6)(7)(8)(9). While CD4 + T-cells and macrophages are dominant in granulomatous lesions of GCA, CD8 + T and natural killer cells are also involved in TAK (7).…”

Section: Large Vessel Vasculitismentioning

confidence: 99%

Jak Inhibitors in the Treatment of Systemic Vasculitides

Alıbaz-Öner¹

2023

qrheumatol

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INTRODUCTIONVasculitides are chronic systemic inflammatory diseases characterized by inflammation of the blood vessel wall. The etiopathogenesis of vasculitis is poorly understood. Among different classification efforts, definition according to the involved vessel size is still the most widely accepted and used one (1). Other than involved vessel size, systemic vasculitis also differ in terms of epidemiology, clinical manifestations, treatment, and prognosis. Glucocorticoids (GCs) are still the mainstay of treatment in systemic vasculitides. Immunosuppressive agents such as cyclophosphamide, rituximab, azathiopurine, and mycophenolate mofetil are chosen as steroid sparing agents according to the type of vasculitis. Biologic treatments such as tumor necrosis factor (TNF) inhibitors and tocilizumab are used in particularly large vessel vasculitis (LVVs) for refractory patients. Cytokine receptors are divided into several superfamilies according to their shared structural elements (2). Janus kinase (JAK) and signal transduction activator of transcription (STAT) are the main players of a cellular transduction pathway named JAK/STAT. The JAK/STAT pathway is one of the important pathways involved in intracellular signal transduction. Type I and II cytokines use this pathway. They are involved in many

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“…We have previously reported innate and adaptive immune profiles in vasculitis by broad immunophenotyping and whole blood RNA sequencing [ 20 – 25 ]. A comparison of patients with LVV with healthy controls (HCs) revealed characteristic upregulation of the IL-1 signaling pathway in those with LVV, associated with the extent of disease and poor prognosis, suggesting an association between the pathogenesis of LVV and innate inflammation [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

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

Matsumoto

Suzuki

Yoshida³

et al. 2023

Arthritis Res Ther

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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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Longitudinal monitoring of circulating immune cell phenotypes in large vessel vasculitis

Cited by 4 publications

References 117 publications

Changes in the molecular profiles of large-vessel vasculitis treated with biological disease-modifying anti-rheumatic drugs and Janus kinase inhibitors

Changes in the molecular profiles of large-vessel vasculitis treated with biological disease-modifying anti-rheumatic drugs and Janus kinase inhibitors

Jak Inhibitors in the Treatment of Systemic Vasculitides

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

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