老年人不明原因发热伴消耗性综合征:两例炎症小体失调的 VEXAS 综合征。

IF 3.4 3区 医学 Q3 IMMUNOLOGY
Leonardo Oliveira Mendonça, Vinicius N C Leal, Mariela E G V Roa, Samar Freschi Barros, Jorge Kalil, Alessandra Pontillo
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引用次数: 0

摘要

本研究的目的是调查 VEXAS 患者外周血白细胞中的炎性体失调。研究人员分析了两名典型UBA1突变的巴西患者的外周血白细胞和中性粒细胞中炎症小体的构成性激活和体外触发激活,并与健康供体进行了比较。我们的研究结果表明,VEXAS白细胞中的caspase-1被持续激活,同时血浆中的IL-18水平升高。此外,在对分离的外周血单核细胞(PBMC)和中性粒细胞进行刺激时,我们不仅观察到 VEXAS PBMC 中 NLRP3 和 NLRP1/CARD8 通路的耗竭,还观察到 VEXAS 中性粒细胞中 NLRP3 介导的 NETs 释放显著增加。这些发现支持了之前关于炎性体对VEXAS发病机制的贡献的研究,确定了VEXAS外周血中至少有两种途径(NLRP3和NLRP1/CARD8)受到严重影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Unexplained fever with consumptive syndrome in the elderly: two cases of VEXAS syndrome with inflammasome dysregulation.

The aim of this study is to investigate the inflammasome dysregulation in peripheral blood leukocytes of VEXAS patients. The constitutive and in vitro triggered activation of inflammasome in PBMC and neutrophils was analyzed in two Brazilian patients with typical UBA1 mutations, and compared with healthy donors. Our findings highlight the constitutive activation of caspase-1 in VEXAS leukocytes, accompanied by increased plasma levels of IL-18. Furthermore, upon stimulation of isolated peripheral blood mononuclear cells (PBMC) and neutrophils, we observed not only the exhaustion of NLRP3 and NLRP1/CARD8 pathways in VEXAS PBMC but also a significant increase in NLRP3-mediated NETs release in VEXAS neutrophils. These findings support previous studies on the contribution of the inflammasome to VEXAS pathogenesis, identifying at least two profoundly affected pathways (NLRP3 and NLRP1/CARD8) in VEXAS peripheral blood.

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来源期刊
CiteScore
8.40
自引率
2.20%
发文量
101
审稿时长
3-8 weeks
期刊介绍: Clinical & Experimental Immunology (established in 1966) is an authoritative international journal publishing high-quality research studies in translational and clinical immunology that have the potential to transform our understanding of the immunopathology of human disease and/or change clinical practice. The journal is focused on translational and clinical immunology and is among the foremost journals in this field, attracting high-quality papers from across the world. Translation is viewed as a process of applying ideas, insights and discoveries generated through scientific studies to the treatment, prevention or diagnosis of human disease. Clinical immunology has evolved as a field to encompass the application of state-of-the-art technologies such as next-generation sequencing, metagenomics and high-dimensional phenotyping to understand mechanisms that govern the outcomes of clinical trials.
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