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血清硫醇作为狼疮性肾炎疾病活动的生物标志物。

Serum thiols as a biomarker of disease activity in lupus nephritis.

作者信息

Lalwani Pritesh, de Souza Giselle Katiane Bonfim Bacelar, de Lima Domingos Savio Nunes, Passos Luiz Fernando Souza, Boechat Antonio Luiz, Lima Emerson Silva

机构信息

Programa de Pós-Graduação em Ciências Farmacêuticas (PPGCF), Universidade Federal do Amazonas, Manaus, Brazil; Centro de Pesquisa Leônidas e Maria Deane (CPqL&MD)-FIOCRUZ, Amazônia, Manaus, Brazil.

Programa de Pós-Graduação em Ciências Farmacêuticas (PPGCF), Universidade Federal do Amazonas, Manaus, Brazil; Faculdade de Ciências Farmacêuticas, Universidade Federal do Amazonas, Manaus, Brazil.

出版信息

PLoS One. 2015 Mar 23;10(3):e0119947. doi: 10.1371/journal.pone.0119947. eCollection 2015.

Abstract

Lupus Nephritis (LN) develops in more than half of the Systemic Lupus Erythematous (SLE) patients. However, lack of reliable, specific biomarkers for LN hampers clinical management of patients and impedes development of new therapeutics. The goal of this study was to investigate whether oxidative stress biomarkers in patients with SLE is predictive of renal pathology. Serum biochemical and oxidative stress markers were measured in patients with inactive lupus, active lupus with and without nephritis and compared to healthy control group. To assess the predictive performance of biomarkers, Receiver Operating Characteristic (ROC) curves were constructed and cut-offs were used to identify SLE patients with nephritis. We observed an increased oxidative stress response in all SLE patients compared to healthy controls. Among the several biomarkers tested, serum thiols had a significant inverse association with SLE Disease Activity Index (SLEDAI). Interestingly, thiols were able too aptly differentiate between SLE patients with and without renal pathology, and serum thiol levels were not affected by immunosuppressive drug therapy. The decreased thiols in SLE correlated significantly with serum creatinine and serum C3 levels. Further retrospective evaluation using serum creatinine or C3 levels in combination with thiol's cutoff values from ROC analysis, we could positively predict chronicity of renal pathology in SLE patients. In summary, serum thiols emerge as an inexpensive and reliable indicator of LN, which may not only help in early identification of renal pathology but also aid in the therapeutic management of the disease, in developing countries with resource poor settings.

摘要

超过半数的系统性红斑狼疮(SLE)患者会发生狼疮性肾炎(LN)。然而,缺乏用于LN的可靠、特异性生物标志物阻碍了患者的临床管理,并妨碍了新疗法的开发。本研究的目的是调查SLE患者的氧化应激生物标志物是否可预测肾脏病理情况。对无活动期狼疮患者、有或无肾炎的活动期狼疮患者测定血清生化和氧化应激标志物,并与健康对照组进行比较。为评估生物标志物的预测性能,构建了受试者工作特征(ROC)曲线,并使用临界值来识别患有肾炎的SLE患者。我们观察到,与健康对照组相比,所有SLE患者的氧化应激反应均增强。在测试的几种生物标志物中,血清硫醇与SLE疾病活动指数(SLEDAI)呈显著负相关。有趣的是,硫醇能够很好地区分有和没有肾脏病理改变的SLE患者,并且血清硫醇水平不受免疫抑制药物治疗的影响。SLE患者硫醇水平降低与血清肌酐和血清C3水平显著相关。通过使用血清肌酐或C3水平结合ROC分析中硫醇的临界值进行进一步的回顾性评估,我们可以阳性预测SLE患者肾脏病理的慢性化。总之,血清硫醇成为LN的一种廉价且可靠的指标,这不仅可能有助于早期识别肾脏病理情况,还可能有助于在资源匮乏环境的发展中国家对该疾病进行治疗管理。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/07a8/4370429/e15f41335392/pone.0119947.g001.jpg

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