Association of Serum Estrodiol Levels with Oral Lichen Planus in Postmenopausal Women - A Comparative Study.

To investigate the expression and clinical significance of miRNA-155 and miRNA-146a in peripheral blood mononuclear cells (PBMC) and plasma of oral lichen planus (OLP) patients. Twenty-five female and seven male OLP patients (OLP group) aged 25 to 54 years were selected from January 2012 to May 2013. The diagnosis was confirmed by pathology and the lesions were divided into two non-erosive OLP group (18 cases) and erosive OLP group (14 cases). Twenty healthy sex and age matched volunteers served as control. miRNA-155 and miRNA-146a expressions in PBMC and plasma were examined by real-time PCR. The difference between OLP group and control group was statistically analyzed. The expressions of PBMC and plasma miRNA-155 were higher in OLP patients than those in the healthy control (median, 0.07 vs 0.03, P < 0.05; 5.84 vs 1.32, P < 0.01). The median expression level of miRNA-146a in PBMC and plasma of OLP patients and healthy controls were (1.26 vs 0.58, P < 0.05) and (412.60 vs 238.42, P < 0.01). The plasma miRNA-155 and miRNA-146a expressions were significantly higher in erosive OLP group than those in non-erosive OLP group. There were no significant differences in the expression of PBMC miRNA-155 and miRNA-146a between the two groups. The expressions of PBMC and plasma miRNA-155 and miRNA-146a are higher in OLP patients. The expressions of plasma miRNA-155 and miRNA-146a are associated with OLP severity. The over expression of miRNA-155 and miRNA-146a in OLP may play a role in the pathogenesis of OLP.

Background and Objectives: Oral lichen planus (OLP) is a common T-cell-mediated inflammatory oral mucosal disease. One of the complaints among OLP patients is xerostomia. However, the relationship between oral dryness and a decreased salivary-flow rate in these patients is not yet conclusive. So, we investigated oral dryness and the salivary-flow rate in OLP patients using various measurements. Material and Methods: Thirty OLP patients and 30 controls were included. The oral-dryness symptoms were collected using the Xerostomia Inventory (XI) and Bother Index (BI). The salivary-flow rate was measured using a Modified Schirmer Test (MST) and the spitting method. The clinical signs of dry mouth were determined by the clinical oral-dryness score (CODS). The Thongprasom score was used to evaluate the severity of OLP. The data were analyzed using the Mann-Whitney U test and Spearman’s rank correlation coefficient. Results: The XI score and BI score in the OLP group were significantly higher than in the control group. However, CODS, MST, the unstimulated salivary-flow rate, and the stimulated salivary-flow rate were not significantly different between the two groups. There was no correlation between oral dryness and the salivary-flow rate in OLP patients. The severity of OLP was also not correlated to oral dryness and the salivary-flow rate. Conclusion: OLP patients had more complaints about mouth dryness than the controls. However, the salivary-flow rates between the two groups were not different. Additionally, the severity of OLP was not related to dry mouth or the salivary-flow rate. The possible reasons for oral dryness among people with OLP require further investigation.

To characterize the bacterial community from different oral niches (buccal mucosa and saliva) in oral lichen planus (OLP) patients. This preliminary study analyzed site-specific (mucosa and saliva) microbial landscape of 20 OLP patients and 10 healthy controls. The microbial diversity was similar between OLP patients and healthy controls in both salivary and mucosal communities. However, the topological properties of co-occurrence networks of salivary and mucosal microbiome were different between healthy controls and OLP patients. SparCC analysis inferred three and five keystone taxa in the salivary and mucosal microbial networks of healthy controls, respectively. However, in the salivary and mucosal bacterial networks of OLP patients, only one hub OTU and three OTUs were identified as keystone taxa, respectively. In addition, analysis of community cohesion revealed that mucosal microbial community in OLP patients had lower stability than that in healthy controls. In final, correlation assay showed that the clinical severity of OLP was positively associated with the relative abundance of Rothia in saliva but negatively associated with that of Porphyromonas on mucosa. The salivary and mucosal bacterial communities of OLP patients differ in terms of composition, the genera associated with OLP severity, and co-occurrence patterns.

ObjectivesThe aim of this study was to: (1) investigate the expression patterns of antimicrobial peptides (AMPs), specifically psoriasin (S100A7) and calgranulin A and B (S100A8/A9), in patients with oral lichen planus (OLP) compared to healthy individuals; (2) evaluate the oral health-related quality of life (OHrQoL) in OLP patients versus healthy controls; (3) investigate the impact of clinical severity of OLP on OHrQoL; and (4) assess the influence of AMP expression on clinical severity and OHrQoL in OLP patients.Materials and methodsOral mucosal biopsies (n = 38) were collected from healthy individuals (n = 17) and patients with OLP (n = 21). Levels of AMPs (S100A7, S100A8, S100A9) and pro-inflammatory cytokines interleukin-8 (IL-8) and tumor necrosis factor alpha (TNFα) were assessed by RT-qPCR. AMP protein localization was identified by indirect immunofluorescence analysis. OHrQoL was assessed using the OHIP-G14 questionnaire, and clinical severity was evaluated with the Oral Disease Severity Score (ODSS). Correlations between OLP manifestation, OHrQoL, and AMP expression were evaluated.Results(1) S100A7 (p < 0.001), IL-8 (p < 0.001), and TNFα (p < 0.001) mRNA levels were significantly upregulated in OLP tissue compared to healthy tissue, while S100A8 (p < 0.001) and S100A9 (p < 0.001) mRNA levels were downregulated. Immunofluorescence staining revealed an enhanced expression of S100A7 and decreased protein expression of S100A9 in OLP tissue. (2) OLP patients (9.58 ± 8.32) reported significantly higher OHIP-G14 scores compared to healthy individuals (0.67 ± 0.87; p < 0.001), particularly in the categories “physical pain” (p < 0.001) and “psychological discomfort” (p = 0.025). (3,4) Clinical severity (25.21 ± 9.77) of OLP correlated positively with OHrQoL (ρ = 0.497) and psoriasin expression (ρ = 0.402).ConclusionsThis study demonstrated differential expression patterns of AMPs in OLP and highlighted the correlation between the clinical manifestation of OLP and OHrQoL. Further research approaches should address the role of psoriasin in the risk of malignant transformation of OLP.Clinical relevancePsoriasin is a putative biomarker to monitor disease severity including malignant transformation of OLP lesions. OHIP-G14 scores can be useful to monitor OHrQoL in OLP patients.

BackgroundEmerging evidence emphasized the role of oral microbiome in oral lichen planus (OLP). To date, no dominant pathogenic bacteria have been identified consistently. It is noteworthy that a decreased abundance of Streptococcus, a member of lactic acid bacteria (LAB) in OLP patients has been commonly reported, indicating its possible effect on OLP. This study aims to investigate the composition of LAB genera in OLP patients by high-throughput sequencing, and to explore the possible relationship between them.MethodsWe collected saliva samples from patients with OLP (n = 21) and healthy controls (n = 22) and performed 16 S rRNA gene high-throughput sequencing. In addition, the abundance of LAB genera was comprehensively analyzed and compared between OLP and HC group. To verify the expression of Lactococcus lactis, real time PCR was conducted in buccal mucosa swab from another 14 patients with OLP and 10 HC. Furthermore, the correlation was conducted between clinical severity of OLP and LAB.ResultsOLP and HC groups showed similar community richness and diversity. The members of LAB, Lactococcus and Lactococcus lactis significantly decreased in saliva of OLP cases and negatively associated with OLP severity. In addition, Lactococcus and Lactococcus lactis showed negative relationship with Fusobacterium and Aggregatibacter, which were considered as potential pathogens of OLP. Similarly, compared with healthy controls, the amount of Lactococcus lactis in mucosa lesion of OLP patients was significantly decreased.ConclusionsA lower amount of Lactococcus at genus level, Lactococcus lactis at species level was observed in OLP cases and associated with disease severity. Further studies to verify the relationship between LAB and OLP, as well as to explore the precise mechanism is needed.

Oral lichen planus (OLP) is a T-cell-mediated inflammatory disease. Interleukin (IL)-8 is a pro-inflammatory cytokine of host response to injury and inflammation. To investigate whether serum IL-8 level was a more sensitive marker than serum IL-6 level in monitoring the disease activity of OLP and to assess whether IL-8 was a useful serum marker in evaluating the therapeutic effects of levamisole on OLP patients. In this study, we used a solid phase, two-site sequential chemiluminescent immunometric assay to determine the baseline serum levels of IL-6 and IL-8 in 158 patients with OLP, nine patients with traumatic ulcers (TU) and 54 normal control subjects. Some OLP patients with the serum IL-6 or IL-8 levels higher than the upper limit of normal serum concentration were treated with levamisole for 0.5-6.0 months and their serum IL-6 and IL-8 levels were measured after treatment. We found that 28% (44 of 158) OLP, 28% (40 of 142) erosive OLP (EOLP), and 25% (four of 16) nonerosive OLP (NEOLP) patients had a serum IL-6 level greater than the upper normal limit of 4.7 pg mL(-1). In contrast, 63% (99 of 158) OLP, 63% (90 of 142) EOLP and 56% (nine of 16) NEOLP patients had a serum IL-8 level greater than the upper normal limit of 8.7 pg mL(-1). In some OLP patients with the serum IL-6 or IL-8 levels higher than the upper limit of normal serum concentration, treatment with levamisole for a period of 0.5-6.0 months could significantly reduce the mean serum IL-6 level from 14.3 +/- 1.9 pg mL(-1) to 3.2 +/- 0.6 pg mL(-1) (P < 0.001) and could significantly reduce the mean serum IL-8 level from 95.8 +/- 17.1 pg mL(-1) to 14.8 +/- 5.8 pg mL(-1) (P < 0.001). Because measurement of the serum IL-8 level can detect more OLP patients with an abnormal serum level than measurement of the serum IL-6 level (63% vs. 28%), we conclude that serum IL-8 level is a more sensitive marker than serum IL-6 level in monitoring the disease activity of OLP. Levamisole can modulate both the serum IL-6 and IL-8 levels in OLP patients. IL-8, like IL-6, is also a useful serum marker in evaluating the therapeutic effects of levamisole on OLP patients.

To determine the structure and co-occurrence patterns of mucosal fungal community in oral lichen planus (OLP) patients. Mucosal swab samples from 20 OLP patients and 10 healthy controls (HCs) were collected and the mucosal mycobiomes were sequenced. The abundance, frequency, and diversity of fungi were analyzed, as well as the inter-genera interactions. The associations between fungal genera and OLP severity were further identified. At the genus level, the relative abundance of unclassified_Trichocomaceae was significantly decreased in the reticular and erosive OLP groups compared to HCs. Meanwhile, significantly lower levels of Pseudozyma were observed in the reticular OLP group compared to HCs. The negative:positive cohesiveness ratio was significantly lower in the OLP group than HCs, indicating a relatively unstable fungal ecological system in the OLP group. In the OLP group, the abundance of unclassified_Nectriaceae was significantly correlated with the reticulation/erythema/ulceration (REU) score. Compared to HCs, the decreased stability of fungal communities and the decreased abundances of two genera (unclassified_Trichocomaceae and Pseudozyma) on buccal mucosa were identified in OLP patients.

Increasing CCL5/CCR5 on CD4+ T cells in peripheral blood of oral lichen planus

This study considered a possible relationship between the severity of oral lichen planus (OLP), serum anti-TPO autoantibodies (TPOAb) titer and thyroid disease in OLP patients. Forty-six OLP patients with positive TPOAb results (> 35 IU/ml) who had also been diagnosed with thyroid disease were included in the study group. The control group consisted of 46OLP patients with no thyroid disease. The study and control groups (92) were divided to two subgroups of erosive OLP (EOLP) and non-erosive OLP (NEOLP). Serum TPOAb levels and IL-8 (to measure OLP severity) were evaluated using the independent t-test, chi-square and conditional logistic regression analysis (α = 0.05). A significant positive correlation was found between serum IL-8 and TPOAb levels in the study group (r = 0.783; p = 0.001). The positive blood levels of TPOAb were significantly associated with an increased risk of EOLP (OR = 4.02 at 95%CI; 1.21-13.4; p = 0.023). It is possible to used positive serum TPOAb levels in patients with OLP as in indicator of possible undetected thyroid disorders in those patients. Because erosive OLP has been associated with TPOAb in thyroid patients, it may be useful to determine TPOAb levels of such patients to diagnose a possible undetected thyroid disorders and follow-up for malignancy.

The present study evaluated the oral tissue expression of micro-RNA (miRNAs) linked to the potential malignant evolution of oral lichen planus (OLP). Furthermore, the correlation between OLP severity and miRNAs expression was assessed, and possible predictors of miRNAs in OLP patients were identified. The present study enrolled 41 patients with OLP (median age 58 years) and 42 healthy controls (median age 59 years). In each patient, miRNA levels (miR-7a-3p,-7a2-3p,-7a-5p,-21-3p,-21-5p,-100-3p,-100-5p,-125b-2-3p,-125b-5p,-200b-3p,-200b-5p) were assessed and analyzed through reverse transcription polymerase chain reaction. Clinical parameters and the eventual presence of OLP symptoms, signs, and disease severity scores in each patient were reported using an anamnestic questionnaire. In comparison with healthy controls, OLP patients showed significantly higher miR-7a-3p,-7a-2-3p,-21-3p, miR-21-5p and miR-100-5p levels (p < 0.05) and significantly lower miR-125b-2-3p,-125b-5p,-200b-3p, and -200b-5p levels (p < 0.05). Furthermore, OLP symptoms and signs and disease severity scores were significantly correlated and were also predictors of all analyzed miRNAs (p < 0.05). In comparison with healthy subjects, OLP patients exhibited unbalanced oral miRNAs expression linked to the risk of potential malignant evolution of OLP. Furthermore, some miRNAs were correlated with OLP extent and were significant predictors of OLP symptoms, signs, and disease severity scores.

ObjectivesExamine the responsibility of Vitamin D (VD) deficit as a risk element in the development and severity of oral lichen planus (OLP) considering dietary habits, sex, sun exposure, socioeconomic class and psychological factors.Materials and methodsBlood samples from 35 OLP patients and 35 healthy controls were collected for the analysis of serum VD level (SVDL) by ELISA. Vitamin D deficiency was considered when SVDL was ≤ 20 ng/ml. Additionally, a structured questionnaire was used to analyze other possible confounders.ResultsSVDL were statistically significant greater in the control group than the OLP group (P ≤ 0.001). There was difference between the 3 types of OLP with statistical significance in which the least values for SVDL were in erosive type (P ≤ 0.001). Furthermore, no statistically significant difference was found in SVDL between dysplastic and non-dysplastic lesions. In terms of VD deficiency, a statistically significant distinction was noticed between the two research sets (P ≤ 0.001) and was more pronounced in erosive and atrophic types than reticular types. Depression as well as sun exposure significantly affected number of patients having VD deficiency (P = 0.001, 0.027). Results revealed a statistically significant direct relation between SVDL and the OLP (odds ratio = 1.38; 95%CI = 1.18–1.617).ConclusionVD deficiency plays a vital role in OLP and the development of more severe forms.Clinical relevanceIt corroborates that VD deficiency is a probable risk factor of OLP and the development of more severe forms considering many confounders.

Increased cyclooxygenase 2 expression in association with oral lichen planus severity

Background: Oral Lichen planus (OLP) is a T-cell mediated chronic inflammatory oral mucosal disease of unknown etiology. Recent studies have reported an increased oxidative stress and lipid peroxidation in such patients. This suggests that reactive oxygen species may have a role in the pathogenesis of lichen planus. Oxidative stress in OLP release molecules consisting of granzymes resulting in local tissue damage in the effectors. Antioxidants that can defend against oxidative stress in the body cells include enzymes, as well as non- enzymatic antioxidants, such as melatonin, uric acid, vitamin A and E. Purpose: To study the level of salivary vitamin E and uric acid as antioxidant agents in patients with OLP and compared with healthy control. Methods: Twenty five patients with OLP were enrolled in this study. Age, gender, occupation, smoking status (smokers or non-smokers), lesion types, duration, location and size were recorded for each patient. After an oral examination, salivary samples were collected and flow rates (ml/min) were recorded. The collected samples were centrifuged at 3000 rpm for 10 minutes; the clear supernatants were separated and stored frozen at (-20 c) until analysis. Then salivary vitamin E was investigated using ELISA kit based on bioten double antibody sandwich technology. Uric acid was analyzed using a proprietary enzymatic reaction mixture that enables the detection of uric acid by the production of a red chromogen, which is quantitatively measured at a wavelength of 515 or 520 nm. Results: The mean age of OLP patients was 48.3 years with a range of 30-60 years. Control group consisted of 35 healthy subjects who were age matched with OLP patients. Fourteen (56%) patients were with reticular and 11 (44%) were with erosive form, with the buccal mucosa was the most commonly affected site (88%), followed by tongue (8%) then gingiva (4%). A significantly lower salivary flow-rate, lower salivary vitamin E and uric acid level in OLP patients compared to control; while, no significant difference was seen between reticular and erosive type of OLP for both vitamin E and uric acid level. Regarding gender, no differences were found between males and females in salivary vitamin E. No significant correlation was found between vitamin E /uric acid and age. Similarly, no difference was found between males and females in uric acid. Conclusion: Salivary anti-oxidant markers represented by vitamin E and uric acid decreased in OLP patients due to increase oxidative stress which may have an important role in the pathogenesis. Thus, it is recommended to give OLP patients anti-oxidant agents that may either help in healing process or decreased the severity.

Oral lichen planus (OLP) is a chronic and T cell-mediated autoimmune disease whose immunopathogenesis may involve antigen-presentation, T cells activation and migration as well as keratinocytes apoptosis. PD-1/B7-H1 pathway may have a unique function in regulating self-reactive T cells associated with inflammatory response and maintaining tolerance in peripheral tissues. In this study, we aimed to explore the contribution of PD-1/B7-H1 pathway to OLP. We determined the expression of PD-1 and B7-H1 on peripheral blood T cells from OLP cases and analyzed their association with disease severity assessed by RAE (reticular, atrophic and erosive lesion) scoring system. In addition, interferon-γ, interleukin (IL)-2, IL-4, IL-10 and soluble PD-1 concentrations in serum were measured using ELISA. Then, we explored the regulation of PD-1/B7-H1 pathway on T cells immune response in OLP by blockade of PD-1 or B7-H1. We found that PD-1 and B7-H1 were up-regulated on peripheral blood T cells from OLP patients and B7-H1 expression positively correlated with disease severity of OLP. It is suggested that Th1 dominant inflammatory situation might contribute to the high expression of PD-1 and B7-H1 in OLP. Blockade of PD-1/B7-H1 pathway significantly increased the proliferation, and IFN-γ and IL-2 production of T cells. PD-1/B7-H1 pathway may play an important role in negatively modulating T cell-mediated immune response in OLP, and provide the rationale to employ B7-H1 expression on peripheral blood T cells as a marker of severity of OLP and to develop agonists targeting PD-1/B7-H1 pathway as a promising immunotherapeutic strategy for OLP.

BackgroundOral lichen planus (OLP) is a T-cell-mediated autoimmune disease that affects the epithelial cells of the oral cavity. This study was performed to investigate any possible relationship between − 1031(T/C) polymorphism (rs1799964) of the tumor necrosis factor α (TNF-α) gene with the risk and severity of oral lichen planus (OLP) disease among an Iranian population.MethodSaliva samples were collected from 100 patients with OLP and a similar number of healthy controls (age and sex-matched). Then, DNA was extracted from the collected samples for genotyping TNF-α-1031 T/C polymorphism using the PCR-CTPP method. The results were assessed using SPSS software.ResultsThe findings revealed a significantly higher prevalence of the C allele in OLP patients (53%) compared to healthy controls (36%), suggesting an association between TNF-alpha gene polymorphism and OLP. A multivariate logistic regression analysis supported this finding, as the presence of the C allele was significantly associated with an increased risk of OLP [χ2 = 4.17, p = 0.04, 95% CI = 1.01–2.65, OR = 1.64]. However, our data indicated no significant association between TNF-alpha-1031 T/C gene polymorphism and OLP severity.ConclusionsThese findings provide the first evidence supporting a possible role of TNF-α-1031 T/C gene polymorphism in OLP susceptibility in the Iranian population. The findings of this study demonstrate a positive association between TNF-α-1031 C/T allele distribution and the risk of OLP disease in the Iranian population. Therefore, carrying the C allele may increase the susceptibility to OLP disease.