IL-2、IL-1O在口腔扁平苔藓发病中的作用

目的：通过对口腔扁平苔藓（OLP）局部组织及外周血中IL-2、IL-10表达进行研究,进-步探讨OLP发病机制。方法：应用免疫组织化学SABC法检测30例OLP中IL-2、IL-10的表达数量及分布,同时用ELISA法检测外周血中IL-2、IL-10的含量。结果：①在病损组织中,OLP组中IL-2、IL-10表达显著高于对照组（P〈0．05）。IL-2主要分布在淋巴细胞浸润带,在基底膜附近较集中;IL-10主要分布在固有层,远离基底膜。②在外周血中,糜烂型OLP组IL-2、IL-10含量明显高于对照组和非糜烂型OLP组（P〈O．05）。结论：①根据IL-2、IL-10在OLP中表达和分布情况,提示IL-2、IL-10在OLP发病机制中参与了机体免疫的调节和介导作用。②外周血中IL-10高表达,提示糜烂型OLP患者全身的免疫反应参与了本病的形成或可能伴有全身免疫系统功能紊乱。     

补血活血法调节口腔扁平苔藓患者红细胞免疫功能的研究

目的：探讨补血活血中药对口腔扁平苔藓(OLP)患者红细胞免疫功能即红细胞-C3b受体花环率(RBC-C3bRR)、红细胞免疫复合物花环率(RBC-ICR)的调节作用，为临床用药提供依据。方法：50例OLP患者随机分为2组，分别给予补血活血中药和雷公藤总甙片进行治疗．采用酵母多糖法检测治疗前后RBC-C3bRR、RBC-ICR的变化。结果：治疗2个月后补血活血中药对OLP患者的黏膜斑纹改善方面明显优于雷公藤总甙片；可提高RBC-3bRR．降低RBC-ICR．从而调节红细胞免疫功能：还显示患者黏膜充血及白斑程度越重，RBC-ICR就越高。结论：OLP患者因病情不同红细胞免疫低下的程度也不同：补血活血中药是治疗OLP有效的并具有凋节红细胞免疫功能的药物。     

口腔扁平苔藓患者血清总干扰素及外周血单个核细胞诱生γ-干扰素活性水平的研究

干扰素(IFN)是由IFN诱生剂诱导有关生物细胞所产生的一类高活性多功能诱生蛋白,能影响机体的体液及细胞免疫功能,参与机体的免疫调控。IFN—γ的产生反应了细胞供者的免疫状态。我们对口腔扁平苔藓(OLP)患者及健康对照成人血清总IFN水平及外周血单个核细胞经PHA诱生IFN—γ水平进行检测。结果发现,OLP组血清IFN与诱生IFN—γ呈正相关性(p<0.05)。推测IFN—γ增高诱导角朊细胞表达HLA—Ⅱ类抗原,促进细胞毒性T细胞及自然杀伤细胞、巨噬细胞的毒性,在OLP发病机理中具有重要意义。     

口腔扁平苔藓的精神发病因素与神经免疫的研究进展

口腔扁平苔藓(OLP)存在多种发病机制假说,其中精神因素发病机制认为,精神因素可以通过应激轴引起神经免疫反应导致OLP的发生,本文就对精神因素以及神经免疫与OLP的关系等研究进展作一综述。     

细胞凋亡相关蛋白Bcl-2对OLP病损区淋巴细胞聚集的影响

目的:探讨凋亡相关蛋白Bcl-2在口腔扁平苔藓(OLP)病变中的生物学行为及对OLP皮损中浸润淋巴细胞聚集、分布的影响,进一步了解OLP的发病机制。方法:采用免疫组织化学检测法,与正常口腔黏膜对照,观察分析25例OLP皮损中Bcl-2蛋白的表达水平及淋巴细胞聚集、分布。结果:OLP病损区T细胞中Bcl-2过度表达,固有层淋巴细胞异常克隆、聚集,浸润增加。结论:OLP病损区中T细胞高密度聚集可能是Bcl-2诱导的局部淋巴细胞过度增殖后关联反应。     

口腔扁平苔藓免疫学因素的研究现状

口腔扁平苔藓(OLP)是一种严重影响患者身心健康的发生于口腔黏膜的非传染性炎症性疾病.OLP的病因尚不明确,可能与多种因素有关.目前的研究表明,OLP的发病与免疫因素密切相关,它是一种以T淋巴细胞介导的免疫应答为特征的慢性疾病.抗原特异性机制和非特异性机制可能参与OLP的免疫过程.首先由树突状细胞摄取、处理未知抗原触发...     

口腔扁平苔藓患者红细胞免疫粘附功能与循环免疫复合物的初步研究

本文旨在探讨口腔扁平苔藓(OLP)患者红细胞免疫粘附功能与OLP发病过程的关系。对80名OLP患者和60名健康对照组的C3b花环、免疫复合物花环、循环免疫复合物三个项目进行检测,结果OLP组红细胞C3b受体花环率和红细胞免疫复合物花环率降低,循环免疫复合物阳性率上升,与对照组比较有显著性差异。提示OLP患者的红细胞免疫粘附功能减退可能与OLP的发病过程有关。     

口腔黏膜扁平苔藓患者口腔黏膜组织中cyclin D1,ki-67及凋亡的表达研究

目的　检测口腔黏膜扁平苔藓 (OLP)患者口腔黏膜上皮凋亡增殖状况及细胞周期调控蛋白表达水平的变化 ,探讨OLP发病机制。方法　采用甲基绿 -派诺宁法及免疫组化SABC法分别检测 30例OLP患者及 2 0例正常对照者口腔黏膜组织的凋亡情况及细胞周期蛋白 (cyclinD1)、增殖细胞核抗原 (ki 6 7)的表达并进行细胞计数及统计学分析。结果　OLP组与对照组凋亡、ki 6 7、cyclinD1表达阳性率差异有显著性 (P <0 .0 5 ) ;与凋亡呈正相关。结论　OLP病变中 ,部分细胞受损进入凋亡性细胞死亡 ,同时发生了细胞周期紊乱、细胞增殖     

口腔扁平苔藓患者血清中白细胞介素-12和白细胞介素-27表达与免疫功能的相关性

目的了解口腔扁平苔藓（OLP）患者血清中白细胞介素（IL）-12和IL-27的表达与患者免疫功能状况的相关性,探讨IL-12和IL-27在OLP免疫发病机制中的作用及意义。方法 选取对照组健康者20例和OLP组患者30例（其中网纹型15例,糜烂型15例）,通过流式细胞术分析OLP患者外周血淋巴细胞亚群CD3+、CD4+、CD8+、CD19+、CD16+56[自然杀伤细胞（NK）]的表达情况,散射比浊法检测患者体液免疫指标免疫球蛋白（Ig）G、IgA、IgM、C3、C4的表达情况。采用酶联免疫吸附试验（ELISA）方法检测血清中IL-12和IL-27的表达水平,分析IL-12和IL-27的表达与OLP患者免疫功能状况及临床特征的相关性。结果 与实验室标准值相比,OLP患者细胞免疫中CD3+、CD4+、CD8+水平降低,CD19+水平增高（P<0.05）;体液免疫中IgM水平增高,C4水平降低（P<0.05）。OLP患者血清中IL-12与IL-27表达水平均高于对照组（P<0.05）。同时相关分析显示,OLP患者血清中IL-12和IL-27的表达水平呈正相关关系（r=0.912,P<0.01）。但是IL-12及IL-27表达水平与OLP体征计分、病程计分等临床特征无相关性（P>0.05）。OLP患者中IL-12和IL-27的表达与CD16+56（NK）存在负相关关系（r₁=-0.416,P₁=0.022;r₂=-0.392,P₂=0.032）,与IgG存在正相关关系（r₁=0.445,P₁=0.014;r₂=0.549,P₂=0.002）。结论OLP患者主要以细胞免疫功能低下为主,同时伴有一定程度的体液免疫功能的紊乱。IL-12和IL-27的异常高表达可能协同引起且促进了OLP的炎症发生发展,并且通过机体代偿性负反馈作用参与了对炎症性免疫应答的调节,在OLP的发病机制中起到了一定作用。     

口腔黏膜病临床治疗Ⅳ.口腔扁平苔藓的诊断及治疗进展

口腔扁平苔藓(oral lichen planus,OLP)是一种伴有慢性浅表性炎症的黏膜角化异常性疾病,发病率约为0.51%,是口腔黏膜病中常见的疾病之一[1]。笔者对2429例黏膜病初诊病例进行统计分析发现,OLP占16.3%(395/2429),仅次于复发性阿弗它溃疡的18.7%(454/2429),居初诊患者的第二位。目前,OLP的发病机制仍不明确,但许多证据表明OLP符合自身免疫性疾病的基本特征[1-5]:①OLP常呈反复发作,呈慢性迁延趋势;②好发于中年女性,且发病部位对称;③OLP的发生有一定的遗传倾向;④糖皮质激素或其他免疫抑制剂治疗OLP常能使病情缓解但不能根治;⑤患者…     

Immunohistochemical study of oral lichen planus associated with hepatitis C virus infection,oral lichenoid contact sensitivity reaction and idiopathic oral lichen planus

OBJECTIVES: Oral lichen planus (OLP) is a common mucocutaneous disorder and might be associated to a possible pathogenic relationship with hepatitis C virus (HCV) infection or hypersensitivity to dental alloy. We examined the clinical and immunohistochemical features of OLP associated with HCV infection (OLP-HCV), oral lichenoid contact sensitivity reaction (OLCSR), and idiopathic oral lichen planus (iOLP). The immunohistochemical expressions of CD4, CD8, B cells, Class II major histocompatibility complex antigen (HLA-DR), S-100, HSP60, Proliferating cell nuclear antigen (PCNA) and Ki-67 were compared to study the pathogenic differences of the three OLP groups. MATERIALS AND METHODS: Three groups of OLP patients, (I) OLP-HCV patients (n = 17), (2) OLCSR patients (n = 10) and (3) iOLP patients (n = 14) were retrieved from clinical records and tissues examined immunohistochemically by the avidin-biotin-complex technique. RESULTS: The patients with OLP-HCV showed widespread lesions. The proportion of CD8+ cells was found to be significantly higher in the lamina propria of the OLP-HCV patients and a significantly lower proportion of CD8+ cells of the OLCSR patients was noticed in the epithelium or the connective tissue papillae than in the iOLP patients. There were no significant differences in either the number of CD4+ cells or B cells between the three OLP groups. No significant differences in the number of HLA-DR+ cells were found between the three OLP groups and some OLP-HCV patients showed a significant increase of S-100+ cells in the epithelium compared with iOLP patients. There were no significant differences in either the number of PCNA+ or Ki-67+ cells between the groups. The patients showed similar weak expressions of HSP60 in the three OLP groups. CONCLUSION: The different distributions of the CD8+ cells that could have functionally different roles might be related to the distinct pathogenic mechanisms in the three OLP groups.     

HLA-DR and DQ antigens in Chinese patients with oral lichen planus

A study of HLA-DR and DQ typing in 44 patients with oral lichen planus (OLP) (28 women and 16 men) and in 107 normal controls of both sexes was performed by using Terasaki's oriental tray. Twenty-eight patients had erosive forms of lichen planus (OLPe). Serologic typing revealed a highly significant increase of HLA-DR 9 and Te 22 antigens in the patient group. Considering our findings and those in other autoimmune diseases, it is hypothesized that OLP is a localized autoimmune disease and the HLA-DR9 in Chinese takes the place of HLA-DR3 in Caucasians in carrying the genes which predispose to the development of autoimmune disease.     

中药Ⅰ号口服液治疗口腔白斑的临床研究

目的　观察中药Ⅰ号口服液治疗口腔白斑的效果。方法　将 6 0例口腔白斑患者随机分成两组 ,治疗组口服中药Ⅰ号口服液 ,对照组按常规治疗。结果　治疗组总有效率为 10 0 % ,治愈率为 70 % ;对照组有效率为 4 0 % ,无治愈。两组对比有显著差异 (P <0 0 1)。结论　中药Ⅰ号口服液能治愈口腔白斑。     

Modulation of serum gastric parietal cell antibody level by levamisole and vitamin B12 in oral lichen planus

Oral Diseases (2010) 17 , 95–101 Objectives: The objective of this study was to test the efficacy of three different treatment modalities on the reduction of serum anti‐gastric parietal cell autoantibody (GPCA) level in GPCA‐positive oral lichen planus (OLP) patients. Materials and methods: Of 147 GPCA‐positive OLP patients, 100 were treated with levamisole plus vitamin B12, 10 with vitamin B12 only and 37 with levamisole only. The serum GPCA levels in 147 OLP patients were measured at baseline and after treatment. Results: Treatment with levamisole plus vitamin B12 for a period of 2–50 months and treatment with vitamin B12 only for a period of 4–44 months could effectively reduce the high serum GPCA level to undetectable level in 100 and 10 OLP patients, respectively. However, treatment with levamisole only for a period of 2–50 months could not modulate the high mean serum GPCA titer to a significantly lower level in 37 OLP patients. A 92% GPCA recurrence rate was found in 25 OLP patients receiving no further vitamin B12 treatment during the GPCA‐negative remission period. Conclusion: For GPCA‐positive OLP patients, treatment modality containing vitamin B12 can effectively reduce the high serum GPCA level to undetectable level. OLP patients with underlying autoimmune atrophic gastritis trait should receive a maintenance vitamin B12 treatment for life.     

Hepatitis C virus‐associated oral lichen planus: is the geographical heterogeneity related to HLA‐DR6?

BACKGROUND: The association between hepatitis C virus (HCV) and oral lichen planus (OLP) is more common in the Mediterranean area and Japan, possibly because of immunogenetic factors. METHODS: Intermediate-resolution HLA-DRB typing by hybridization with oligonucleotide probes was performed in 31 Italian OLP patients with HCV infection, in 45 Italian OLP and in 48 British OLP patients without HCV infection. As healthy controls we included data from 145 unrelated Italian and 101 unrelated British bone marrow donors. RESULTS: Italian HCV+ve OLP patients possessed the HLA-DR6 allele more frequently than Italian and British OLP patients without HCV infection (51.6% vs. 17.7% vs. 16.7%; P corrected = 0.028 and 0.017, respectively). There was no difference in the frequency of the HLA-DR6 allele between Italian and British control subjects. CONCLUSIONS: The present data suggest that HLA-DR6 may be responsible for the peculiar geographic heterogeneity of the association between HCV and OLP.     

TL1A和IDO在口腔扁平苔藓患者外周血中的表达研究

目的 研究肿瘤坏死因子样配体1A（tumor necrosis factor-like ligand 1A,TL1A）和吲哚胺2,3双加氧酶（indoleamine 2,3-dioxygenase,IDO）在口腔扁平苔藓（OLP）患者外周血中的表达及其是否存在相关性。方法 采用实时荧光定量聚合酶链反应（FQ-PCR）法检测30例OLP患者和30例健康人外周血单个核细胞中TL1A、IDO的基因表达水平。结果 在OLP患者中,TL1A、IDO的基因表达水平均高于对照组（P＜0.05）,结果经2-ΔΔCT转换后,OLP组TL1A、IDO mRNA表达水平分别是健康对照组的1.7872、2.0763倍。TL1A、IDO mRNA的表达水平无明显相关性（P>0.05）。结论 TL1A、IDO mRNA在OLP的发病中起了一定作用,两者的作用机制有待于进一步研究。     

Heat shock protein expression in oral lichen planus

To assess the potential role of heat shock protein (HSP) in the pathogenesis of oral lichen planus (OLP), sections of OLP, normal oral mucosa, non-specific oral ulceration (NSOU) and dysplastic OLP were assessed for HSP expression using avidin-biotin complex immunohistochemistry with an anti-HSP 70 polyclonal antibody. There were statistically significant differences in both the vertical and horizontal staining distribution when other groups were compared with the OLP group (p<0.01). Using microdensitometry, the mean staining intensity in OLP, dysplastic OLP and NSOU was elevated in comparison with normal oral mucosa (p<0.001). In a standard tritiated thymidine uptake assay, lymphocytes extracted from nine OLP lesions demonstrated significant proliferation when stimulated with purified protein derivative (PPD), of which HSP is a major constituent, with stimulation indices ranging from 2 to 132. These results are consistent with the hypothesis that, in OLP patients, diverse exogenous agenst may cause upregulated expression of HSP by oral mucosal keratinocytes. A reaction of cytotoxic T lymphocytes to these activated keratinocytes may then result in the tissue destruction which is characteristic of OLP lesions.     

Altered microRNA expression profile with miR-27b down-regulation correlated with disease activity of oral lichen planus

Oral Diseases (2012) 18 , 265–270 Background: Increasing evidence indicates that microRNAs (miRNAs) play a vital role in the pathogenesis of inflammatory and autoimmune diseases. The objective of this study was to investigate the altered miRNA expression profile in patients with oral lichen planus (OLP) and determine the miR‐27b expression. Methods: We compared miRNA expression patterns in oral biopsy specimens from patients with OLP (n = 3) with those from normal controls (n = 3) using microarray technology. We further assessed the miR‐27b expression in specimens from patients with OLP (n = 53) against controls (n = 34) using real‐time quantitative PCR (RT‐QPCR), and miR‐27b expression in specimens from patients with OLP (n = 15) against controls (n = 12) using in situ hybridization (ISH). Results: Using microarray analysis, a total of 46 differentially expressed miRNAs with more than 2‐fold change were identified, including 8 up‐regulated and 38 down‐regulated miRNAs. Both RT‐QPCR and ISH analyses revealed that miR‐27b was significantly down‐regulated in OLP tissue, and miR‐27b expression was even more suppressed in atrophic‐erosive OLP than in reticular OLP. In addition, miR‐27b was found to be expressed in the epithelial keratinocyte layer of both normal and OLP tissues. Conclusion: These data indicate that miRNAs may be the novel candidate biomarkers for the implication of miRNAs in the pathogenesis of OLP.     

Cytokine production by keratinocytes and mononuclear infiltrates in oral lichen planus

Cytokine generation by tissue-infiltrating mononuclear cells (TIMC) and by keratinocytes (KC) was investigated in material obtained from the oral mucosal tissues of patients with oral lichen planus (OLP). Peripheral blood mononuclear cells (PBMC) and chronically inflamed and noninflamed gingival KC (CIG-KC, NOR-KC, respectively) were used as the controls. Compared to NOR-KC and CIG-KC, KC from OLP patients (OLP-KC) produced much more interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and granulocyte-macrophage colony-stimulating factor (GM-CSF). The OLP-KC superiority in the production of these cytokines was more prominent when the KC were cultured in the presence of interleukin-l beta (IL-1β), lipopolysaccharide and phorbol myristate acetate. OLP-KC also produced more monocyte-chemotactic factor(s) which were not inactivated by the antibodies against GM-CSF, macrophage colony-stimulating factor and monocyte chemoattractant protein-1. TIMC in OLP tissues (OLP-TIMC) were superior to PBMC in the generation of IL-6 and GM-CSF. OLP-TIMC were stimulated to produce more TNF-a by IL-1β, IL-6 and GM-CSF, more IL-6 by IL-1β and GM-CSF, and more GM-CSF by IL-1β and IL-6 than PBMC. When compared to cytokine generation in TIMC from the chronically inflamed gingivae, more interferon-gamma, IL-6 and TNF-α were generated by OLP-TIMC. These results indicate that KC play a critical role in OLP, producing cytokines including monocyte-chemotactic factor(s), and that the cytokines produced by TIMC and OLP-KC through autocrine and paracrine processes enhance the local inflammatory response.     

PD-L1mRNA与PD-L2mRNA在口腔扁平苔藓中的表达特点及可能作用

目的:研究PD-L1mRNA、PD-L2mRNA在口腔扁平苔藓(oral lichen planus,OLP)患者外周血与损害组织,以及在不同临床类型与病理分型中的表达特点。方法:采用实时定量PCR方法检测60例OLP患者(斑纹型35例,充血糜烂型25例;不伴异常增生38例,伴轻度异常增生22例)PD-L1mRNA、PD-L2mRNA表达水平,并以10名正常人外周血与黏膜组织作为对照,比较不同临床类型和病理类型OLP患者间PD-L1mRNA、PD-L2mRNA表达水平差异,并分析PD-L1mRNA、PD-L2mRNA在OLP患者外周血与损害组织中表达的相关性。利用SAS6.12软件包中的非配对两样本均数比较的Wilcoxon秩和检验,比较不同组别间的差异。结果:PD-L2mRNA在OLP患者外周血中表达降低,损害组织中表达升高,且在不同临床类型OLP患者之间存在显著差异(P<0.05)。PD-L1mRNA在OLP组与正常对照组之间的表达差异无统计学意义(P>0.05)。结论:PD-L2分子可能在OLP患者全身与损害局部对OLP的发生、发展产生不同的影响。