The target on B cells in Systemic Sclerosis: a “midsummer dream” to extinguish inflammation and prevent early disease progression to fibrosis

Luca, Giacomo De; Tomelleri, Alessandro; Dagna, Lorenzo; Matucci‐Cerinic, Marco

doi:10.1007/s10067-021-05733-4

Cited by 6 publications

(10 citation statements)

References 38 publications

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“…1 B cells are important in the progression of SSc, 2-4 and many clinical studies have shown the usefulness of rituximab (RTX) for SSc-ILD. [4][5][6][7] However, there is a lack of research for predictive factors that influence RTX effect on SSc-ILD. In rheumatoid arthritis and systemic lupus erythematosus, the degree of B-cell removal after RTX has been reported to predict treatment efficacy.…”

mentioning

confidence: 99%

Percentage of residual B cells after 2 weeks of rituximab treatment predicts the improvement of systemic sclerosis‐associated interstitial lung disease

Ebata

Yoshizaki

Fukasawa

et al. 2021

The Journal of Dermatology

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The benefit of rituximab (RTX) for systemic sclerosis‐associated interstitial lung disease (SSc‐ILD) has been shown in previous clinical trials. However, predictors of RTX efficacy have not been clarified. We investigated whether B‐cell responsiveness to RTX is related to therapeutic effect. Ten SSc‐ILD patients treated with RTX in an independent clinical trial (Japan Registry of Clinical Trials, jRCTs031180373) were included in this analysis. Peripheral B‐cell counts were examined retrospectively before RTX administration (baseline) and at 2, 4, 12, and 24 weeks after the first RTX administration, along with percent‐predicted forced vital capacity (%FVC) before and 24 weeks after RTX treatment. Relative to baseline, the percentage of residual peripheral blood B cells at 2 weeks after RTX was negatively correlated with the %FVC improvement at the 24‐week assessment (r = −0.41, p = 0.04). In the subgroup with less than 5% B‐cell persistence at week 2, %FVC at the 24‐week assessment was significantly improved compared to baseline (p = 0.02). In another subgroup with more than 5% residual B cells, %FVC was not significantly different after 24 weeks compared to baseline (p = 0.41). In conclusion, the removal rate of B cells after 2 weeks of RTX treatment may be a useful surrogate marker of subsequent SSc‐ILD improvement.

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mentioning

confidence: 99%

Percentage of residual B cells after 2 weeks of rituximab treatment predicts the improvement of systemic sclerosis‐associated interstitial lung disease

Ebata

Yoshizaki

Fukasawa

et al. 2021

The Journal of Dermatology

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“…SSc pathogenesis is closely associated with inflammatory abnormalities in the initial phase of fibrosis [ 38 ]. Bleomycin-induced SSc involves dysregulation of levels of proinflammatory cytokines [ 19 , 39 ].…”

Section: Resultsmentioning

confidence: 99%

“…Considering that inflammation occurs in the early stage of fibrosis and is strongly responsible for the development of SSc [ 38 ], we measure the anti-inflammatory efficacy of baicalein in bleomycin-induced SSc. Some pro-inflammatory/inflammatory cytokines and chemokines, such as IL-4, IL-6, IL-10, MCP-1, and MIP-1, are at high levels in the blood, skin, and lungs.…”

Section: Discussionmentioning

confidence: 99%

Baicalein alleviates fibrosis and inflammation in systemic sclerosis by regulating B-cell abnormalities

Peng

et al. 2023

BMC Complement Med Ther

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Background Systemic sclerosis (SSc; also known as “scleroderma”) is an autoimmune disorder characterized by extensive fibrosis, vascular changes, and immunologic dysregulation. Baicalein (phenolic flavonoid derived from Scutellaria baicalensis Georgi) has been used to treat the pathological processes of various fibrotic and inflammatory diseases. In this study, we investigated the effect of baicalein on the major pathologic characteristics of SSc: fibrosis, B-cell abnormalities, and inflammation. Methods The effect of baicalein on collagen accumulation and expression of fibrogenic markers in human dermal fibroblasts were analyzed. SSc mice were produced by injecting bleomycin and treated with baicalein (25, 50, or 100 mg/kg). The antifibrotic features of baicalein and its mechanisms were investigated by histologic examination, hydroxyproline assay, enzyme-linked immunosorbent assay, western blotting and flow cytometry. Results Baicalein (5–120 μM) significantly inhibited the accumulation of the extracellular matrix and fibroblast activation in transforming growth factor (TGF)-β1- and platelet derived growth factor (PDGF)-induced human dermal fibroblasts, as evidenced by abrogated deposition of total collagen, decreased secretion of soluble collagen, reduced collagen contraction capability and downregulation of various fibrogenesis molecules. In a bleomycin-induced model of dermal fibrosis in mice, baicalein (25–100 mg/kg) restored dermal architecture, ameliorated inflammatory infiltrates, and attenuated dermal thickness and collagen accumulation in a dose-dependent manner. According to flow cytometry, baicalein reduced the proportion of B cells (B220+ lymphocytes) and increased the proportion of memory B cells (B220+CD27+ lymphocytes) in the spleens of bleomycin-induced mice. Baicalein treatment potently attenuated serum levels of cytokines (interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-17A, tumor necrosis factor-α), chemokines (monocyte chemoattractant protein-1, macrophage inflammatory protein-1 beta) and autoantibodies (anti-scleroderma 70 (Scl-70), anti-polymyositis-scleroderma (PM-Scl), anti-centromeres, anti-double stranded DNA (dsDNA). In addition, baicalein treatment can significantly inhibit the activation of TGF-β1 signaling in dermal fibroblasts and bleomycin-induce mice of SSc, evidenced by reducing the expression of TGF-β1 and IL-11, as well as inhibiting both small mother against decapentaplegic homolog 3 (SMAD3) and extracellular signal-related kinase (ERK) activation. Conclusions These findings suggest that baicalein has therapeutic potential against SSc, exerting modulating B-cell abnormalities, anti-inflammatory effects, and antifibrosis.

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“…These cytokines polarized activity of CD4 T cells into Th2, Tfh and/or Th17. Increased of Th2 cytokines then enhanced autoantibody production from plasma cells and contribute to collagen production from fibroblast [28][29][30].…”

Section: Adaptive Immunitymentioning

confidence: 99%

Current Update on the Role of Inflammation in the Pathogenesis of SSc

Elvira,

Masri

2023

Systemic Sclerosis - Recent Advances and New Perspectives

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Systemic sclerosis (SSc), also known as scleroderma, is a systemic autoimmune rheumatic disease characterized by dysregulation of the immune system, fibrosis of the skin and visceral organs, and vasculopathy. Inflammatory activation may be important in the initiation and progression of vasculopathy and fibrosis in response to homeostatic disturbance. Numerous factors trigger and enable sustained inflammation such as increased oxidative stress, involved in progressivity and disease severity. This chapter will focus on the role of inflammation and the involvement of multiple immune mediators contributing to autoimmune activity of SSc.

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The target on B cells in Systemic Sclerosis: a “midsummer dream” to extinguish inflammation and prevent early disease progression to fibrosis

Cited by 6 publications

References 38 publications

Percentage of residual B cells after 2 weeks of rituximab treatment predicts the improvement of systemic sclerosis‐associated interstitial lung disease

Percentage of residual B cells after 2 weeks of rituximab treatment predicts the improvement of systemic sclerosis‐associated interstitial lung disease

Baicalein alleviates fibrosis and inflammation in systemic sclerosis by regulating B-cell abnormalities

Current Update on the Role of Inflammation in the Pathogenesis of SSc

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