Immunohistochemical Expression of Immune Regulatory Proteins in Interface Dermatoses.

IF 1.6 4区 医学 Q3 DERMATOLOGY
Sarah Grace McAlpine, Donna Culton, Michael Duplisea, Zhi Liu, Si On Lim, Paul Googe
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Abstract

Cutaneous immune-related adverse events (irAEs) of immunotherapies, such as anti-programmed cell death protein-1 (PD-1), suggest that immune checkpoint factors may contribute to the pathobiology of lichenoid interface dermatitis in immunotherapy-naïve patients. Our study aimed to describe innate and adaptive immune markers via immunohistochemical (IHC) staining of lichenoid interface dermatoses. We studied the staining patterns of PD-L1, STING, IL-36 gamma, CD8, PD-1, and LAG-3 in five interface dermatoses: oral lichen planus (LP) (n = 10), cutaneous LP (n = 10), chronic cutaneous lupus erythematosus (CLE) (n = 11), erythema multiforme (EM) (n = 11), and toxic epidermal necrolysis (TEN) (n = 13), by immunohistochemistry (IHC) analysis. Expression was evaluated semi-quantitively according to the percentage of keratinocytes and dermal lymphocytes stained compared to keratinocytes and resident pericapillary lymphocytes in normal human skin. All interface dermatoses evaluated showed increased expression of PD-L1 on keratinocytes and LAG-3 in lymphocytes. STING was increased on the keratinocytes of most specimens. Expression of IL-36 gamma, in basal layer keratinocytes was more extensive in oral LP and cutaneous LP and varied in CLE, EM, and TEN. Lymphocytic infiltration expressing PD-1 was elevated in oral LP, cutaneous LP, and CLE. Current thinking is that interface dermatitis is the result of a cell-mediated immune reaction involving cytotoxic CD8+ T-cell-mediated apoptosis of keratinocytes. The findings of this study suggest that in addition to cell-mediated immunity, innate immune factors may contribute to pathobiology.

界面皮肤病中免疫调节蛋白的免疫组化表达。
抗程序性细胞死亡蛋白-1(PD-1)等免疫疗法引起的皮肤免疫相关不良事件(irAEs)表明,免疫检查点因子可能是免疫疗法无效患者苔癣样界面皮炎的病理生物学因素之一。我们的研究旨在通过对苔癣样界面性皮炎进行免疫组织化学(IHC)染色来描述先天性和适应性免疫标记物。我们通过免疫组化(IHC)分析,研究了五种界面性皮肤病中 PD-L1、STING、IL-36 γ、CD8、PD-1 和 LAG-3 的染色模式:口腔扁平苔藓(LP)(n = 10)、皮肤扁平苔藓(LP)(n = 10)、慢性皮肤红斑狼疮(CLE)(n = 11)、多形性红斑(EM)(n = 11)和中毒性表皮坏死(TEN)(n = 13)。与正常人皮肤中的角朊细胞和常驻毛细血管周围淋巴细胞相比,根据染色的角朊细胞和真皮淋巴细胞的百分比对表达进行半定量评估。所有接受评估的界面皮肤病都显示角朊细胞中的 PD-L1 和淋巴细胞中的 LAG-3 表达增加。大多数标本的角朊细胞中 STING 表达增加。IL-36 gamma在基底层角质细胞中的表达在口腔LP和皮肤LP中更为广泛,在CLE、EM和TEN中则有所不同。表达 PD-1 的淋巴细胞浸润在口腔 LP、皮肤 LP 和 CLE 中升高。目前的观点认为,界面性皮炎是细胞介导的免疫反应的结果,包括细胞毒性 CD8+ T 细胞介导的角质细胞凋亡。本研究的结果表明,除了细胞介导的免疫反应外,先天性免疫因素也可能对病理生物学起作用。
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来源期刊
CiteScore
3.20
自引率
5.90%
发文量
174
审稿时长
3-8 weeks
期刊介绍: Journal of Cutaneous Pathology publishes manuscripts broadly relevant to diseases of the skin and mucosae, with the aims of advancing scientific knowledge regarding dermatopathology and enhancing the communication between clinical practitioners and research scientists. Original scientific manuscripts on diagnostic and experimental cutaneous pathology are especially desirable. Timely, pertinent review articles also will be given high priority. Manuscripts based on light, fluorescence, and electron microscopy, histochemistry, immunology, molecular biology, and genetics, as well as allied sciences, are all welcome, provided their principal focus is on cutaneous pathology. Publication time will be kept as short as possible, ensuring that articles will be quickly available to all interested in this speciality.
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