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皮肤狼疮红斑皮肤活检中的 IL-1β 和 IL-17:免疫组化是否能表明有全身性受累的倾向?

IL-1β and IL-17 in cutaneous lupus erythematous skin biopsies: could immunohistochemicals indicate a tendency towards systemic involvement?

机构信息

Department of Pathology, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP, Brazil.

Department of Pathology, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP, Brazil.

出版信息

An Bras Dermatol. 2024 Jan-Feb;99(1):66-71. doi: 10.1016/j.abd.2023.02.007. Epub 2023 Sep 30.

Abstract

BACKGROUND

Only a fraction of patients with cutaneous lupus erythematosus (CLE) will eventually progress toward systemic disease (SLE).

OBJECTIVE

To find inflammatory biomarkers which could predict the progression of cutaneous lupus erythematosus (CLE) into systemic lupus erythematosus (SLE) using immunohistochemical (IHC) assays.

METHODS

Immunohistochemical markers for cytotoxic, inflammatory, and anti-inflammatory responses and morphometric methods were applied to routine paraffin sections of skin biopsies, taken from lesions of 59 patients with discoid lupus, subacute lupus, and lupus tumidus. For the diagnosis of SLE, patients were classified by both the American College of Rheumatology (ACR-82) and the Systemic Lupus International Collaborating Clinics (SLICC-12) systems.

RESULTS

Skin samples from CLE/SLE+patients presented higher expression of IL-1β (ARC-82: p=0.024; SLICC-12: p=0.0143) and a significantly higher number of cells marked with granzyme B and perforin (ARC: p=0.0097; SLICC-12: p=0.0148). Biopsies from CLE/SLE- individuals had higher expression of IL-17 (ARC-82: p=0.0003; SLICC-12: p=0.0351) and presented a positive correlation between the density of granzyme A+and FoxP3+ cells (ARC-82: p=0.0257; SLICC-12: p=0.0285) and CD8+ cells (ARC-82: p=0.0075; SLICC-12: p=0.0102), as well as between granulysin-positive and CD8+ cells (ARC-82: p=0.0024; SLICC-12: p=0.0116).

STUDY LIMITATIONS

Patients were evaluated at a specific point in their evolution and according to the presence or not of systemic disease. The authors cannot predict how many more, from each group, would have evolved towards SLE in the following years.

CONCLUSIONS

In this cohort, immunohistochemical findings suggested that patients with a tendency to systemic disease will show strong reactivity for IL-1β, while those with purely cutaneous involvement will tend to express IL-17 more intensely.

摘要

背景

只有一小部分盘状红斑狼疮(CLE)患者最终会发展为系统性红斑狼疮(SLE)。

目的

使用免疫组织化学(IHC)检测寻找可预测皮肤红斑狼疮(CLE)向系统性红斑狼疮(SLE)进展的炎症生物标志物。

方法

对 59 例盘状狼疮、亚急性狼疮和狼疮性丘疹患者皮损的石蜡切片进行免疫组化标记物检测,评估细胞毒性、炎症和抗炎反应以及形态计量学方法。为了诊断 SLE,患者根据美国风湿病学会(ACR-82)和系统性红斑狼疮国际合作诊所(SLICC-12)系统进行分类。

结果

CLE/SLE+患者的皮肤样本中,IL-1β的表达更高(ACR-82:p=0.024;SLICC-12:p=0.0143),且颗粒酶 B 和穿孔素标记的细胞数量显著增加(ARC:p=0.0097;SLICC-12:p=0.0148)。CLE/SLE-患者的皮肤活检中,IL-17 的表达更高(ACR-82:p=0.0003;SLICC-12:p=0.0351),并且颗粒酶 A+和 FoxP3+细胞(ARC-82:p=0.0257;SLICC-12:p=0.0285)和 CD8+细胞(ARC-82:p=0.0075;SLICC-12:p=0.0102)之间以及粒细胞蛋白阳性细胞与 CD8+细胞之间呈正相关(ARC-82:p=0.0024;SLICC-12:p=0.0116)。

研究局限性

患者在其病程中的特定时间点进行评估,根据是否存在系统性疾病进行分组。作者无法预测在接下来的几年中,每组中有多少患者会发展为 SLE。

结论

在本队列中,免疫组化结果表明,倾向于发生系统性疾病的患者 IL-1β反应强烈,而仅表现为皮肤受累的患者则倾向于表达更强烈的 IL-17。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b70f/10964360/c1adaf4fdfb6/gr1.jpg

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