弥漫性系统性硬化症患者的蛋白转化酶枯草杆菌素/键素9 (PCSK9):疾病活动性和严重疾病表现的标志物，具有潜在的治疗实施

IF 1.1 4区医学 Q4 Medicine

Archives of rheumatology Pub Date : 2023-06-01 DOI:10.46497/ArchRheumatol.2023.9638

Joy Artin, Yumn A Elsabagh, Laila Rashed, Mohamed A Hussein

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引用次数: 0

摘要

目的:本研究旨在探讨弥漫系统性硬化症(d-SSc)患者的枯草素/键素9蛋白转化酶(PCSK9)及其与疾病活动性、严重程度和亚临床动脉粥样硬化的关系。患者和方法:2019年12月至2021年7月，共41例d-SSc患者(男性17例，女性24例;平均年龄:36.1±1.9岁;年龄范围19至58岁)和41名年龄和性别匹配的健康对照(17名男性，24名女性;平均年龄:40.1±1.7岁;范围，20至60年)。分别使用欧洲硬皮病研究组(EScSG)评分和改良罗德曼皮肤评分(mRSS)评估患者的疾病活动性和皮肤厚度。采用酶联免疫吸附法(ELISA)和双工超声分别测定血清PCSK9和颈动脉内膜-中膜厚度(CIMT)。结果:患者血清PCSK9水平高于对照组(p=0.003)，特别是患有数字溃疡(DU)和间质性肺疾病(ILD)的患者(p=0.003)。结论:血清PCSK9在d-SSc中上调，在DU和ILD等严重疾病表现中水平较高。它与疾病活动性、更严重的疾病表现和CIMT密切相关。无论其抗胆固醇作用如何，至少在更严重的表现中，PCSK9抑制剂可能是早期动脉粥样硬化疾病(如d-SSc)的治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Proprotein convertase subtilisin/kexin 9 (PCSK9) in patients with diffuse systemic sclerosis: A marker of disease activity and severe disease manifestations with potential therapeutic implementations.

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Objectives: This study aims to investigate proprotein convertase subtilisin/kexin 9 (PCSK9) in patients with diffuse systemic sclerosis (d-SSc) and its relation to disease activity, severity and subclinical atherosclerosis in such group of patients.

Patients and methods: Between December 2019 and July 2021, a total of 41 patients with d-SSc (17 males, 24 females; mean age: 36.1±1.9 years; range, 19 to 58 years) and 41- age and sex-matched healthy controls (17 males, 24 females; mean age: 40.1±1.7 years; range, 20 to 60 years) were included. Disease activity and skin thickness of the patients were evaluated using the European Scleroderma Study Group (EScSG) score and modified Rodnan skin score (mRSS), respectively. Serum PCSK9 and carotid intima-media thickness (CIMT) were measured using enzyme-linked immunosorbent assay (ELISA) and Duplex ultrasound, respectively.

Results: Serum PCSK9 was higher in patients compared to controls (p=0.003), particularly in those with digital ulcer (DU) and interstitial lung disease (ILD) (p<0.001). The PCSK9 positively correlated with the mean pulmonary artery pressure, EScSG, mRSS, C-reactive protein (p<0.001), erythrocyte sedimentation rate (p<0.05), lipid profile, and mean CIMT (p<0.01). In the multivariate analysis, EScSG, mRSS, lipid profile, and waist circumference were significantly correlated with PCSK9. Serum PCSK9 levels of (182.6 ng/mL) had 77.7% sensitivity and 81.2% specificity for diagnosing DU versus (172.8 ng/mL) 90.1% and 73.5% for ILD (p<0.001).

Conclusion: Serum PCSK9 is upregulated in d-SSc with higher levels in severe disease manifestations such as DU and ILD. It is correlated well with disease activity, more severe disease manifestations, and CIMT. The PCSK9 inhibitors may be a target of therapy in diseases with premature atherosclerosis such as d-SSc regardless of its anti-cholesterol effect, at least in more severe manifestations.

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来源期刊

Archives of rheumatology Medicine-Rheumatology

CiteScore

2.00

自引率

9.10%

发文量

期刊介绍： The Archives of Rheumatology is an official journal of the Turkish League Against Rheumatism (TLAR) and is published quarterly in March, June, September, and December. It publishes original work on all aspects of rheumatology and disorders of the musculoskeletal system. The priority of the Archives of Rheumatology is to publish high-quality original research articles, especially in inflammatory rheumatic disorders. In addition to research articles, brief reports, reviews, editorials, letters to the editor can also be published. It is an independent peer-reviewed international journal printed in English. Manuscripts are refereed by a "double-blind peer-reviewed" process for both referees and authors. Editorial Board of the Archives of Rheumatology works under the principles of The World Association of Medical Editors (WAME), the International Council of Medical Journal Editors (ICMJE), and Committee on Publication Ethics (COPE).