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口腔扁平苔藓中PD-L1、PD-L2、PD-1及细胞毒性免疫反应的评估

Evaluation of PD-L1, PD-L2, PD-1 and cytotoxic immune response in oral lichen planus.

作者信息

Costa Nádia Lago, Gonçalves Julie Ane Maria, de Lima Sara Lia Gonçalves, de Arruda José Alcides Almeida, Miranda Ana Carolina Campos, Mesquita Ricardo Alves, da Silveira Éricka Janine Dantas, Batista Aline Carvalho

机构信息

Department of Stomatology (Oral Medicine and Oral Pathology), School of Dentistry, Universidade Federal de Goiás, Goiânia, Brazil.

Department of Oral Surgery and Pathology, School of Dentistry, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.

出版信息

Oral Dis. 2020 Sep;26(6):1246-1254. doi: 10.1111/odi.13344. Epub 2020 Apr 16.

DOI:10.1111/odi.13344
PMID:32259363
Abstract

OBJECTIVE

To investigate the expression of programmed death-ligands 1 and 2 (PD-L1, PD-L2), programmed death-1 (PD-1), CD8 and granzyme B (GrB), as well as its correlation with the severity of oral lichen planus (OLP).

MATERIALS AND METHODS

In a collaborative study, 33 cases of OLP were evaluated according to the latest criteria proposed by the American Academy of Oral and Maxillofacial Pathology (AAOMP/2016) and were submitted to immunohistochemistry. Positivity was measured semiquantitatively (PD-L1, PD-L2) and quantitatively (PD-1, CD8, GrB). The severity of OLP was assessed according to clinical subtype, symptomatology and response to corticosteroid therapy.

RESULTS

Most OLPs were considered to be negative for PD-L1 (66.6%), but high expression of PD-L2 (96.9%) by keratinocytes and immunoinflammatory cells was observed. PD-1 cell density/mm was reduced compared to CD8 cells. A low cytotoxic immune response (CD8:GrB ratio) was also demonstrated. Interestingly, there were fewer GrB cells in the intraepithelial region in reticular OLP compared to erosive/bullous OLP.

CONCLUSIONS

PD-L1/PD-1 pathways appear to be compromised in OLP due to low PD-L1 expression in most samples. In contrast, PD-L2 overexpression associated with a possible regulation of the cytotoxic immune response suggests an immune tolerance that may contribute to the chronic profile of OLP.

摘要

目的

研究程序性死亡配体1和2(PD-L1、PD-L2)、程序性死亡蛋白1(PD-1)、CD8和颗粒酶B(GrB)的表达情况,及其与口腔扁平苔藓(OLP)严重程度的相关性。

材料与方法

在一项合作研究中,根据美国口腔颌面病理学会提出的最新标准(AAOMP/2016)对33例OLP病例进行评估,并进行免疫组织化学检测。对阳性结果进行半定量(PD-L1、PD-L2)和定量(PD-1、CD8、GrB)测量。根据临床亚型、症状及对皮质类固醇治疗的反应评估OLP的严重程度。

结果

大多数OLP病例的PD-L1被认为呈阴性(66.6%),但观察到角质形成细胞和免疫炎症细胞高表达PD-L2(96.9%)。与CD8细胞相比,PD-1细胞密度/mm降低。还显示出低细胞毒性免疫反应(CD8:GrB比率)。有趣的是,与糜烂/大疱性OLP相比,网状OLP上皮内区域的GrB细胞较少。

结论

由于大多数样本中PD-L1表达较低,PD-L1/PD-1通路在OLP中似乎受到损害。相比之下,PD-L2的过表达与细胞毒性免疫反应的可能调节相关,提示免疫耐受可能导致OLP的慢性病程。

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