上海口腔医学 ›› 2021, Vol. 30 ›› Issue (2): 113-119.doi: 10.19439/j.sjos.2021.02.001

• 论著 • 上一篇    下一篇

口腔苔藓样损害中淋巴滤泡样结构表征及免疫细胞组成的实验研究

李晶晶1,2, 宋晨成2, 李晨曦2, 夏荣辉2, 邓一文2, 王宇峰2,*, 唐国瑶1,2,*   

  1. 1.潍坊医学院口腔医学院,山东 潍坊 261021;
    2.上海交通大学医学院附属第九人民医院·口腔医学院 口腔黏膜病科,国家口腔疾病临床医学研究中心, 上海市口腔医学重点实验室,上海市口腔医学研究所,上海 200011
  • 收稿日期:2020-02-17 修回日期:2020-04-21 出版日期:2021-04-25 发布日期:2021-05-11
  • 通讯作者: 唐国瑶,E-mail: tanggy@shsmu.edu.cn;王宇峰,E-mail: dr_wangyufeng@126.com。*共同通信作者
  • 作者简介:李晶晶(1992-),女,在读硕士研究生,E-mail:593287009@qq.com
  • 基金资助:
    国家自然科学基金(81730030、81970937); 上海交通大学医学院附属第九人民医院种子基金(JYZZ046)

Experimental study on the structure and immune cell phenotypes of the lymphoid tissues in oral lichenoid lesions

LI Jing-jing1,2, SONG Chen-cheng2, LI Chen-xi2, XIA Rong-hui2, DENG Yi-wen2, WANG Yu-feng2, TANG Guo-yao1,2   

  1. 1. College of Stomatology, Weifang Medical University. Weifang 261021, Shandong Province;
    2. Department of Oral Medicine, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology. Shanghai 200011, China
  • Received:2020-02-17 Revised:2020-04-21 Online:2021-04-25 Published:2021-05-11

摘要: 目的:评估口腔苔藓样损害(oral lichenoid lesion,OLL)中是否具有三级淋巴结构(tertiary lymphoid structure,TLS),并分析其免疫细胞的组成特征。方法:收集正常口腔黏膜组织、口腔扁平苔藓组织(oral lichen planus, OLP)和口腔苔藓样损害组织(oral lichenoid tissue reaction, OLTR)各30例,行苏木精-伊红(H-E)染色,评估各组织中是否存在TLS样结构。利用免疫组织化学染色鉴定TLS相关的B细胞(CD19+、CD20+)、T细胞(CD3+)、滤泡树突状细胞(CD21+)、生发中心(Bcl-6+)和血管(CD34+ PNAd+)、淋巴管(CD34+ Gp36+)结构在各组中的数量和分布特点。在组织病理和分子标志物水平,评价TLS在OLL中的形态学表现。利用GraphPad Prism 7.0软件对数据进行统计学分析。结果:OLP组和OLTR组中,分别有46.7%(14/30)和23.4%(7/30)的病例存在TLS样结构,TLS样结构出现的频率与疾病类型无关(P>0.05)。与对照组相比,OLP组和OLTR组各分子标志物均高表达,其中,CD19、CD20和CD21在OLP组的表达具有TLS的形态结构特点。OLP组和OLTR组中,Bcl-6(平均积分吸光值分别为15 498±15 108 ∶ 1 841±2 276,P<0.000 1)、CD20(13 067±9 049 ∶ 7 695±5 159,P<0.05)、CD21(13 968±14 560 ∶ 2 552±2 584,P<0.000 1)、PNAd(10 328±10 383 ∶ 1 756±1 570,P<0.000 1)和Gp36(12 778±12 390 ∶ 2 313±2 578,P<0.000 1)的表达水平存在显著差异,但表达差异不能作为鉴别疾病类型的依据。结论:OLL中存在TLS,以非经典TLS为主,可见经典TLS;CD20、CD21可作为鉴定OLL损害组织中TLS的标志物,但TLS不能作为鉴别OLP和OLTR的依据。

关键词: 口腔苔藓样损害, 口腔扁平苔藓, 三级淋巴结构, 淋巴滤泡样结构

Abstract: PURPOSE: To evaluate the existence of tertiary lymphoid structures(TLS) in oral lichenoid lesions and its compositional characteristics of immune cells. METHODS: Tissue samples of normal oral mucosa, oral lichen planus (OLP) and oral lichenoid tissue reaction(OLTR) were collected, thirty cases in each group. Hematoxylin-eosin(H-E) staining was performed to identify the TLS-like structures, and immunohistochemistry (IHC) staining was applied to assess the structure and amount of infiltrating CD3+ T cells, CD19+, CD20+ B cells, CD21+ follicular dendritic cells (FDC), Bcl-6+ germinal centers, CD34+ PNAd+ venules and CD34+ Gp36+ micro lymphatic vessels in TLS of OLL. Histopathology and molecular markers were used to evaluate the morphological performance of TLS in OLL. Chi-square test (Fisher exact probability method) was applied to compare the proportion of TLS in each group; integral optical density (IOD) method was used to calculate the expression level of each molecular marker, nonparametric t test (Mann-Whitney U test) was employed to analyze their difference. Statistical analysis was performed with GraphPad Prism 7.0 software. RESULTS: In OLP group and OLTR group, 46.7% (14/30) and 23.4% (7/30) cases had TLS-like structures, respectively. The frequency of TLS-like structures was not correlated with the type of disease(P>0.05). Compared with the control group, the molecular markers in OLP group and OLTR group were highly expressed, and the expression of CD19, CD20, and CD21 in OLP group had morphological and structural characteristics of TLS. The expression of Bcl-6(mean and standard deviation of IOD were 15 498±15 108 vs. 1 841±2 276, P<0.000 1), CD20 (13 067±9 049 vs. 7 695±5 159, P<0.05), CD21 (13 968±14 560 vs. 2 552±2 584, P<0.000 1), PNAd (10 328±10 383 vs. 1 756±1 570, P<0.000 1) and Gp36 (12 778±12 390 vs. 2 313±2 578, P<0.000 1) showed significant differences between OLP and OLTR tissues, but it could not be used as the criteria for identifying the type of diseases without morphological characters. CONCLUSIONS: TLS exists in OLL lesions, mainly presented as non-classical forms. The classical forms can be occasionally found. CD20 and CD21 can be used as the biomarkers to identify the TLS in OLL. TLS can not be used as the diagnosing criteria for identifying OLP or OLTR.

Key words: Oral lichenoid lesion, Oral lichen planus, Tertiary lymphatic structure, Lymphoid follicle-like structure

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