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银屑病患者中弗林蛋白酶的表达——一个面临新冠病毒风险的患者队列?

Furin Expression in Patients With Psoriasis-A Patient Cohort Endangered to SARS-COV2?

作者信息

Graier Thomas, Golob-Schwarzl Nicole, Weger Wolfgang, Benezeder Theresa, Painsi Clemens, Salmhofer Wolfgang, Wolf Peter

机构信息

Department of Dermatology and Venereology, Medical University of Graz, Graz, Austria.

Department of Dermatology and Venereology, State Hospital, Klagenfurt, Austria.

出版信息

Front Med (Lausanne). 2021 Feb 10;8:624462. doi: 10.3389/fmed.2021.624462. eCollection 2021.

Abstract

SARS-Cov2 has raised concerns among dermatologists regarding psoriasis and its respective treatments. Comorbidities, which induce the expression of the proprotease furin have been associated with severe course of COVID-19. Furin and angiotensin converting enzyme 2 (ACE2) play a major role in viral host cell entry of SARS-Cov2. To evaluate mRNA expression of Furin and ACE2 from blood cells in psoriasis patients, and whether systemic or topical treatment reduces expression levels. This observational translational study analyzed blood samples from patients from a clinical trial and samples retrieved from the biobank of the Psoriasis Registry Austria (PsoRA). Furin and ACE2 expression levels were analyzed prior to as well as 3 and 12-24 months after start of biologic treatment with either ustekinumab or secukinumab. Additionally, the study analyzed expression levels prior to, 6 days after start of dithranol treatment and 4-6 weeks after end of dithranol treatment. Furin mRNA expression was significantly increased at baseline in the biologic (4.9 ± 2.6 fold, < 0.0001) and in the dithranol group (2.7 ± 1.4 fold, < 0.001) compared to controls. There was a trend for arthritis patients to express more furin than patients with psoriatic skin involvement only (5.26 ± 2.30 vs. 3.48 ± 2.27, = 0.078). Analyzing furin mRNA expression after treatment initiation with secukinumab or ustekinumab revealed a normalization of levels after 3 and 12 to 24 months. Similar findings were obtained for patients treated with dithranol, with significantly decreased expression levels 6 days after start of dithranol treatment and also at follow-up, (4-6 weeks after dithranol treatment had been terminated). ACE2 expression levels did not differ from controls at any timepoint, regardless of biologic or topical treatment. Significantly overexpressed levels of furin were observed in untreated patients, and, thus, these patients may be at risk for infection and a severe course of COVID-19. However, the data indicate that successful therapeutic intervention in psoriasis, by systemic biologic or topical treatment, can efficiently reduce furin levels in blood cells, possibly limiting the risk of psoriasis patients for a severe COVID-19 course. ClinicalTrials.gov, identifier NCT02752672.

摘要

严重急性呼吸综合征冠状病毒2(SARS-CoV-2)引发了皮肤科医生对银屑病及其相应治疗的关注。诱导前蛋白酶弗林蛋白酶表达的合并症与COVID-19的严重病程相关。弗林蛋白酶和血管紧张素转换酶2(ACE2)在SARS-CoV-2的病毒宿主细胞进入过程中起主要作用。为了评估银屑病患者血细胞中弗林蛋白酶和ACE2的mRNA表达,以及全身或局部治疗是否会降低表达水平。这项观察性转化研究分析了来自一项临床试验患者的血样以及从奥地利银屑病登记处(PsoRA)生物样本库中获取的样本。在用乌司奴单抗或司库奇尤单抗进行生物治疗开始前、开始后3个月以及12 - 24个月分析弗林蛋白酶和ACE2的表达水平。此外,该研究还分析了地蒽酚治疗开始前、开始后6天以及地蒽酚治疗结束后4 - 6周的表达水平。与对照组相比,生物治疗组基线时弗林蛋白酶mRNA表达显著升高(4.9±2.6倍,<0.0001),地蒽酚组也显著升高(2.7±1.4倍,<0.001)。关节炎患者比仅患有银屑病皮肤病变的患者有表达更多弗林蛋白酶的趋势(5.26±2.30对3.48±2.27,P = 0.078)。分析用司库奇尤单抗或乌司奴单抗治疗开始后弗林蛋白酶mRNA表达发现,3个月以及12至24个月后水平恢复正常。地蒽酚治疗的患者也有类似发现,地蒽酚治疗开始后6天以及随访时(地蒽酚治疗结束后4 - 6周)表达水平显著降低。无论生物治疗还是局部治疗,ACE2表达水平在任何时间点与对照组均无差异。在未治疗的患者中观察到弗林蛋白酶水平显著过表达,因此,这些患者可能有感染风险以及COVID-19的严重病程风险。然而,数据表明,通过全身生物治疗或局部治疗成功干预银屑病,可以有效降低血细胞中的弗林蛋白酶水平,可能降低银屑病患者发生严重COVID-19病程的风险。ClinicalTrials.gov标识符:NCT02752672。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c00e/7902756/b2fed3534939/fmed-08-624462-g0001.jpg

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