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白细胞介素 17E、诱导型一氧化氮合酶和精氨酸酶 1 作为中性粒细胞皮肤病鉴定的新生物标志物。

Interleukin-17E, inducible nitric oxide synthase and arginase1 as new biomarkers in the identification of neutrophilic dermatoses.

机构信息

Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland.

Department of Dermatology, University Hospital CHUV, Lausanne, Switzerland.

出版信息

Clin Exp Dermatol. 2022 Apr;47(4):675-683. doi: 10.1111/ced.14988. Epub 2021 Dec 17.

Abstract

BACKGROUND

Neutrophilic dermatoses (ND) are a heterogeneous group of diseases, but can often have a relatively similar histological appearance.

AIM

To identify a combination of biomarkers allowing a better differentiation of ND types.

METHODS

Biopsies were obtained from normal human skin (NS; n = 4), chronic plaque-type psoriasis (PsO; n = 7), paradoxical psoriasis (PP; n = 8), generalized pustular psoriasis (GPP; n = 9), subcorneal pustular dermatosis of Sneddon-Wilkinson (SPD; n = 3), acute generalized exanthematous pustulosis (AGEP; n = 3), hidradenitis suppurativa (HS; n = 7), Sweet syndrome (SS; n = 8) and pyoderma gangrenosum (PG; n = 8). Samples were analysed by immunofluorescence using three biomarkers, interleukin (IL)-17E, inducible nitric oxide synthase (iNOS) and arginase1, each one in combination with two cell markers, myeloperoxidase (MPO) and CD68, which allow the identification of neutrophils and macrophages, respectively.

RESULTS

We found that SS is characterized by high expression of IL-17E and iNOS in the epidermis, while PG exhibits low expression. The density of the neutrophil infiltrate helps to differentiate PP (high-density infiltrate) from PsO (low-density infiltrate). High expression of arginase1 in the granular layer of the epidermis is a hallmark of SPD. Finally, mature neutrophils and proinflammatory macrophages are readily detectable in PP, SPD and PG, whereas immature neutrophils and anti-inflammatory macrophages are more frequent in GPP, AGEP, HS and SS.

CONCLUSIONS

The analysis of ND by immunofluorescence using IL-17E, iNOS and arginase1 in combination with MPO and CD68 allows for characterization of differential expression patterns in the epidermis as well as the determination of the polarization status of the dermal neutrophils and macrophages. The appropriate markers may help in the differentiation of ND in clinical practice.

摘要

背景

中性粒细胞皮肤病(ND)是一组异质性疾病,但通常具有相对相似的组织学表现。

目的

确定一组生物标志物,以更好地区分 ND 类型。

方法

从正常人类皮肤(NS;n=4)、慢性斑块型银屑病(PsO;n=7)、反常性银屑病(PP;n=8)、泛发性脓疱型银屑病(GPP;n=9)、Sneddon-Wilkinson 亚表皮脓疱病(SPD;n=3)、急性泛发性发疹性脓疱病(AGEP;n=3)、化脓性汗腺炎(HS;n=7)、Sweet 综合征(SS;n=8)和坏疽性脓皮病(PG;n=8)中获取活检样本。使用三种生物标志物(白细胞介素 17E(IL-17E)、诱导型一氧化氮合酶(iNOS)和精氨酸酶 1)通过免疫荧光分析样本,每种生物标志物均与两种细胞标志物(髓过氧化物酶(MPO)和 CD68)联合使用,分别识别中性粒细胞和巨噬细胞。

结果

我们发现 SS 的特征是表皮中 IL-17E 和 iNOS 的高表达,而 PG 则表现出低表达。中性粒细胞浸润的密度有助于区分 PP(高密度浸润)和 PsO(低密度浸润)。表皮颗粒层中精氨酸酶 1 的高表达是 SPD 的标志。最后,在 PP、SPD 和 PG 中容易检测到成熟的中性粒细胞和促炎巨噬细胞,而在 GPP、AGEP、HS 和 SS 中更常见不成熟的中性粒细胞和抗炎巨噬细胞。

结论

使用 IL-17E、iNOS 和精氨酸酶 1 结合 MPO 和 CD68 通过免疫荧光分析 ND 可以对表皮中的差异表达模式进行特征描述,并确定真皮中性粒细胞和巨噬细胞的极化状态。适当的标志物可能有助于在临床实践中区分 ND。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7de3/9300036/4f823288f744/CED-47-675-g004.jpg

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