Eduardo Delabio Auer , Valéria Bumiller-Bini Hoch , Emiliano Borges da Silva , Yohan Ricci Zonta , Luciane Alarcão Dias-Melicio , Thelma Larocca Skare , Vanessa F. Picceli , Iara José Messias-Reason , Angelica Beate Winter Boldt
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NET levels were evaluated in one hundred seventy serum samples of patients with Systemic Lupus Erythematosus (SLE) using an Immunoassay. Univariate and multivariate binary logistic regression used clinical patients' data as independent variables. Parametric and non-parametric tests compared log10 base serum NET levels transformed between patients' groups. SLE patients were also dichotomized into “High serum NET levels” and “Low serum NET levels” groups. All analyses were performed in R language 4.1.2, and <em>p</em> < 0.05 were considered significant. Increased susceptibility for high serum NET levels was observed in SLE patients with Raynaud's phenomenon (OR = 2.30, 95 % CI = 1.06–5.21 and <em>p</em> = 0.039), independently of any other risk factor. Also, SLE patients with Raynaud's phenomenon presented higher mean NET serum levels (mean = −0.13 vs. −0.51, <em>p</em> = 0.01). In addition, higher mean NET serum levels were associated with glomerulonephritis (mean = -0.45 vs. −0.12, <em>p</em> = 0.03). Ultimately, the SLEDAI index scored higher in the high NETs serum levels group (median = 2.0 vs. 0.0, <em>p</em> = 6 × 10<sup>−3</sup>). The formation of NETs might be implicated in Raynaud's phenomenon, glomerulonephritis, and disease index score in SLE patients. Our results highlight the importance of serum NET levels as a possible therapeutical target to modulate the clinical course of SLE.</p></div>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":null,"pages":null},"PeriodicalIF":4.6000,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298524000214/pdfft?md5=2e87b717ec774929921c1e0a21e8600c&pid=1-s2.0-S0171298524000214-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Association of neutrophil extracellular trap levels with Raynaud’s phenomenon, glomerulonephritis and disease index score in SLE patients from Brazil\",\"authors\":\"Eduardo Delabio Auer , Valéria Bumiller-Bini Hoch , Emiliano Borges da Silva , Yohan Ricci Zonta , Luciane Alarcão Dias-Melicio , Thelma Larocca Skare , Vanessa F. Picceli , Iara José Messias-Reason , Angelica Beate Winter Boldt\",\"doi\":\"10.1016/j.imbio.2024.152803\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Neutrophil extracellular traps (NETs) are cell-extruded DNA strands coated with neutrophils' nuclear proteins and enzymes from cytotoxic granules, produced by NETosis, a cell death pathway. They perform an important defensive role in innate immunity, but their increased production and/or inefficient degradation expose new antigens, such as DNA or citrullinated histone peptides, triggering autoimmunity. This study aimed to access possible associations between serum NETs levels with epidemiological, clinical, and serological data from a well-characterized SLE Brazilian patients’ cohort. NET levels were evaluated in one hundred seventy serum samples of patients with Systemic Lupus Erythematosus (SLE) using an Immunoassay. Univariate and multivariate binary logistic regression used clinical patients' data as independent variables. Parametric and non-parametric tests compared log10 base serum NET levels transformed between patients' groups. SLE patients were also dichotomized into “High serum NET levels” and “Low serum NET levels” groups. All analyses were performed in R language 4.1.2, and <em>p</em> < 0.05 were considered significant. Increased susceptibility for high serum NET levels was observed in SLE patients with Raynaud's phenomenon (OR = 2.30, 95 % CI = 1.06–5.21 and <em>p</em> = 0.039), independently of any other risk factor. Also, SLE patients with Raynaud's phenomenon presented higher mean NET serum levels (mean = −0.13 vs. −0.51, <em>p</em> = 0.01). In addition, higher mean NET serum levels were associated with glomerulonephritis (mean = -0.45 vs. −0.12, <em>p</em> = 0.03). Ultimately, the SLEDAI index scored higher in the high NETs serum levels group (median = 2.0 vs. 0.0, <em>p</em> = 6 × 10<sup>−3</sup>). 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引用次数: 0
摘要
中性粒细胞胞外捕获物（NET）是由细胞死亡途径--NETosis--产生的涂有中性粒细胞核蛋白和细胞毒性颗粒酶的细胞挤出 DNA 链。它们在先天性免疫中发挥着重要的防御作用，但其产生的增加和/或降解效率低下会暴露新的抗原，如DNA或瓜氨酸组蛋白肽，从而引发自身免疫。本研究旨在从一个特征明确的巴西系统性红斑狼疮患者队列中，了解血清NETs水平与流行病学、临床和血清学数据之间可能存在的关联。研究人员使用免疫测定法对170名系统性红斑狼疮（SLE）患者的血清样本进行了NET水平评估。单变量和多变量二元逻辑回归将患者的临床数据作为自变量。参数检验和非参数检验比较了患者组间转换后的 log10 基底血清 NET 水平。系统性红斑狼疮患者还被分为 "高血清 NET 水平 "组和 "低血清 NET 水平 "组。所有分析均在 R 语言 4.1.2 中进行，< 0.05 为显著。在患有雷诺现象的系统性红斑狼疮患者中观察到高血清NET水平的易感性增加（OR = 2.30, 95 % CI = 1.06-5.21 and = 0.039），与任何其他风险因素无关。此外，患有雷诺现象的系统性红斑狼疮患者的平均NET血清水平较高（平均=-0.13 vs. -0.51，=0.01）。此外，较高的NET血清平均水平与肾小球肾炎有关（平均值=-0.45 vs. -0.12，=0.03）。最终，高NET血清水平组的SLEDAI指数得分更高（中位数=2.0 vs. 0.0，=6×10）。NET的形成可能与系统性红斑狼疮患者的雷诺现象、肾小球肾炎和疾病指数评分有关。我们的研究结果凸显了血清NET水平的重要性，它可能成为调节系统性红斑狼疮临床病程的治疗目标。
Association of neutrophil extracellular trap levels with Raynaud’s phenomenon, glomerulonephritis and disease index score in SLE patients from Brazil
Neutrophil extracellular traps (NETs) are cell-extruded DNA strands coated with neutrophils' nuclear proteins and enzymes from cytotoxic granules, produced by NETosis, a cell death pathway. They perform an important defensive role in innate immunity, but their increased production and/or inefficient degradation expose new antigens, such as DNA or citrullinated histone peptides, triggering autoimmunity. This study aimed to access possible associations between serum NETs levels with epidemiological, clinical, and serological data from a well-characterized SLE Brazilian patients’ cohort. NET levels were evaluated in one hundred seventy serum samples of patients with Systemic Lupus Erythematosus (SLE) using an Immunoassay. Univariate and multivariate binary logistic regression used clinical patients' data as independent variables. Parametric and non-parametric tests compared log10 base serum NET levels transformed between patients' groups. SLE patients were also dichotomized into “High serum NET levels” and “Low serum NET levels” groups. All analyses were performed in R language 4.1.2, and p < 0.05 were considered significant. Increased susceptibility for high serum NET levels was observed in SLE patients with Raynaud's phenomenon (OR = 2.30, 95 % CI = 1.06–5.21 and p = 0.039), independently of any other risk factor. Also, SLE patients with Raynaud's phenomenon presented higher mean NET serum levels (mean = −0.13 vs. −0.51, p = 0.01). In addition, higher mean NET serum levels were associated with glomerulonephritis (mean = -0.45 vs. −0.12, p = 0.03). Ultimately, the SLEDAI index scored higher in the high NETs serum levels group (median = 2.0 vs. 0.0, p = 6 × 10−3). The formation of NETs might be implicated in Raynaud's phenomenon, glomerulonephritis, and disease index score in SLE patients. Our results highlight the importance of serum NET levels as a possible therapeutical target to modulate the clinical course of SLE.
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