Non-erosive Oral Lichen Planus Research Articles

Microbial Profiles in Oral Lichen Planus: Comparisons with Healthy Controls and Erosive vs. Non-Erosive Subtypes.

Recent studies have begun exploring the potential involvement of microbiota in the pathogenesis of oral lichen planus (OLP), yet comprehensive investigations remain limited. Hence, this study aimed to compare the microbial profiles in saliva samples obtained from patients with OLP against those from healthy controls (HC), along with a comparison between erosive (E) and non-erosive (NE) OLP patients. Saliva samples were collected from 60 OLP patients (E: n = 25, NE: n = 35) and 30 HC individuals. Analysis revealed no significant differences in alpha diversity, as assessed by the Chao1 and Shannon index, across the three groups. However, Bray-Curtis distance analysis indicated a significant disparity in microbiome composition distribution between HC and E-OLP, as well as HC and NE-OLP groups. The six most abundant phyla observed across the groups were Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria, Fusobacteria, and Saccharibacteria (TM7). Notably, OLP groups exhibited a higher prevalence of Bacteroidetes. Prevotella emerged as the predominant genus in the OLP groups, while Capnocytophaga showed a relatively higher prevalence in E-OLP compared to NE-OLP. This study's findings indicate a notable difference in microbiota composition between HC and patients with OLP. Additionally, differences in the microbiome were identified between the E-OLP and NE-OLP groups. The increase in the proportion of certain bacterial species in the oral microbiome suggests that they may exacerbate the inflammatory response and act as antigens for OLP.

CD8+ tissue-resident memory T cells induce oral lichen planus erosion via cytokine network.

CD8+ tissue-resident memory T (CD8+ Trm) cells play key roles in many immune-inflammation-related diseases. However, their characteristics in the pathological process of oral lichen planus (OLP) remains unclear. Therefore, we investigated the function of CD8+ Trm cells in the process of OLP. By using single-cell RNA sequencing profiling and spatial transcriptomics, we revealed that CD8+ Trm cells were predominantly located in the lamina propria adjacent to the basement membrane and were significantly increased in patients with erosive oral lichen planus (EOLP) compared to those with non-erosive oral lichen planus (NEOLP). Furthermore, these cells displayed enhanced cytokine production, including IFN-γ (Interferon-gamma, a pro-inflammatory signaling molecule), TNF-α (Tumor Necrosis Factor-alpha, a cytokine regulating inflammation), and IL-17 (Interleukin-17, a cytokine involved in immune response modulation), in patients with EOLP. And our clinical cohort of 1-year follow-up was also supported the above results in RNA level and protein level. In conclusion, our study provided a novel molecular mechanism for triggering OLP erosion by CD8+ Trm cells to secrete multiple cytokines, and new insight into the pathological development of OLP.

Predicting the Activity of Oral Lichen Planus with Glycolysis-related Molecules: A Scikit-learn-based Function.

Oral lichen planus (OLP) is one of the most common oral mucosa diseases, and is mainly mediated by T lymphocytes. The metabolic reprogramming of activated T cells has been shown to transform from oxidative phosphorylation to aerobic glycolysis. The present study investigated the serum levels of glycolysis-related molecules (lactate dehydrogenase, LDH; pyruvic acid, PA; lactic acid, LAC) in OLP, and the correlation with OLP activity was assessed using the reticular, atrophic and erosive lesion (RAE) scoring system. Univariate and multivariate linear regression functions based on scikit-learn were designed to predict the RAE scores in OLP patients, and the performance of these two machine learning functions was compared. The results revealed that the serum levels of PA and LAC were upregulated in erosive OLP (EOLP) patients, when compared to healthy volunteers. Furthermore, the LDH and LAC levels were significantly higher in the EOLP group than in the nonerosive OLP (NEOLP) group. All glycolysis-related molecules were positively correlated to the RAE scores. Among these, LAC had a strong correlation. The univariate function that involved the LAC level and the multivariate function that involved all glycolysis-related molecules presented comparable prediction accuracy and stability, but the latter was more time-consuming. It can be concluded that the serum LAC level can be a user-friendly biomarker to monitor the OLP activity, based on the univariate function developed in the present study. The intervention of the glycolytic pathway may provide a potential therapeutic strategy.

Expression and significance of microtubule associated protein 1 light chain 3B, p62 and Beclin1 in lesion tissues of oral lichen planus patients

Objective: To explore the expression of autophagy related factors microtubule associated protein 1 light chain 3B (LC3B), p62, autophagy key factor Beclin1 in oral lichen planus (OLP) tissues and their relationships with the clinicopathological characteristics of OLP, investigating the function and significance of autophagy in pathogenesis of OLP. Methods: Forty-one lesion tissues (OLP group, twenty-one cases of erosive OLP and twenty cases of non-erosive OLP) were selected from OLP patients visiting the Department of Periodontal and Oral Medicine, School and Hospital of Stomatology, Guizhou Medical University from October 2017 to December 2019. Fifteen cases of normal oral mucosal tissues (control group) were collected from oral and maxillofacial surgery at The Affiliated Stomatology Hospital of Guizhou Medical University during the same period. Protein and mRNA expression levels of LC3B, p62 and Beclin1 were detected by immunohistochemistry (IHC) and real-time quantitative PCR (RT-qPCR) in OLP lesions respectively. The protein expression levels of LC3B, p62, Beclin1 and ratio of LC3B-Ⅱ/LC3B-Ⅰ in sixteen cases (eight cases of erosive OLP and eight cases of non-erosive OLP) from the OLP group were detected by Western blotting (WB). The potential relationship between LC3B, p62, Beclin1, LC3B-Ⅱ/LC3B-Ⅰ ratio and clinical features of OLP were analyzed. Results: IHC results showed that the positive expression rates of LC3B and p62 proteins in OLP lesion tissues [LC3B: 68% (28/41); p62: 59% (24/41)] were higher than those in the control group [LC3B: 5/15; p62: 3/15] (LC3B: χ2=5.55, P=0.019; p62: χ2=5.55, P=0.015). The positive expression rates of LC3B and p62 proteins in the erosive OLP group [LC3B: 86% (18/21); p62: 76% (16/21)] were higher than those in the non-erosive OLP group [LC3B: 50% (10/20); p62: 40% (8/20)] (LC3B: χ2=4.50, P=0.034; p62:χ2=5.53, P=0.019). The positive expression rate of Beclin1 protein in the OLP lesions[20% (8/41)] was lower than that in the control group (7/15) (χ2=4.13, P=0.042), but was not statistically different between the two types of OLP (P>0.05). The RT-qPCR results showed that the mRNA expression levels of LC3B and p62 in OLP lesions [LC3B: 2.78 (1.59, 6.15); p62: 4.30 (2.34, 6.29)] were higher than those in the control group [LC3B: 1.05 (0.88, 1.21); p62: 1.12 (0.89, 1.36)] (LC3B: Z=-4.56, P<0.001; p62: Z=-4.78, P<0.001), and the mRNA expression levels of LC3B and p62 in the erosive OLP group were higher than those in the non-erosive OLP group (LC3B: Z=-2.87, P=0.004; p62: Z=-2.95, P=0.003). The mRNA expression level of Beclin1 in OLP tissues was lower than that in the control group (Z=-2.43, P=0.015), but the difference was not statistically significant between the two types of OLP (P>0.05). WB results showed that the LC3B-Ⅱ/LC3B-Ⅰ ratio was higher in the OLP lesions than that in the control group (t=-2.45, P=0.021), and the LC3B-Ⅱ/LC3B-Ⅰ ratio was higher in the non-erosive OLP group than in the erosive OLP group (t=-2.38, P=0.032). Spearman's correlation analysis showed that the ratio was negatively correlated with the clinical staging and the degree of basal cell liquefaction in OLP (clinical staging: r=-0.57, P=0.021; basal cell liquefaction: r=-0.54, P=0.032), but not with the disease duration and the degree of lymphocytic infiltration (P>0.05). Conclusions: Autophagy related factors LC3B, p62 and Beclin1 may play a role in the formation and progression of OLP lesions. The autophagy level was relatively lack in erosive OLP compared to non-erosive OLP, contributing to the increased local lesion destruction in erosive OLP. Abnormal cellular autophagy may play an important role in the formation of OLP lesions.

Clinical Evaluation of Dexamethasone Plus Gentamycin Mouthwash Use in Combination with Total Glucosides of Paeony for Treatment of Oral Lichen Planus without Fungal Infection: A Comparative Study with Long-Term Follow-Up.

Background: Oral lichen planus (OLP) is a common chronic inflammatory disease of the oral mucosa and considered a potential malignant disease, for which a method for complete cure is lacking. The dexamethasone and gentamicin mouthwash, combined with total glucosides of paeony (TGP), was tested in the treatment of OLP patients without fungal infection, with a view to provide evidence that may assist in resolving the dilemma. Methods: A randomized and single-blind clinical trial of 48 non-erosive and erosive OLP patients was conducted, with the patients divided into two groups. Group A was treated with dexamethasone plus gentamycin mouthwash and Group B received an additional TGP capsule together with the aforementioned mouthwash. All the patients were followed up with four times, at 2 weeks, 1 month, 3 months, and 6 months. The clinical manifestations, sign score, and VAS scale were recorded. The total effective rate (%) was defined as (cases of complete resolution + cases of partial resolution)/total cases observed × 100%. Results: A total of 43 patients completed all follow-up appointments. Among the 21 patients in Group A, the total effective rate was 61.9%. Of the 22 patients in Group B, the total effective rate was 89.66%. The clinical manifestation, sign score, and VAS of the two groups all indicated improvements, and there were significant differences between the two groups (p < 0.05). Conclusions: Dexamethasone plus gentamycin mouthwash combined with TGP treatment for OLP patients is a safe and effective treatment of OLP.

Autophagy-related 9 homolog B regulates T-cell-mediated immune responses in oral lichen planus

ObjectivesThis study aimed to explore the impacts of autophagy-related 9 homolog B (ATG9B)-mediated autophagy on T-cell immune responses in oral lichen planus. DesignATG9B expression was detected in lesions and local T cells by immunohistochemical analysis and immunofluorescence assay. The effects of ATG9B-mediated autophagy on T-cell immune responses were explored after ATG9B-overexpression or ATG9B-knockdown lentivirus transfection. A coculture system of activated T cells and lipopolysaccharide-induced keratinocytes was used to simulate the main cell crosstalk in oral lichen planus. ResultsThe expression of ATG9B upregulated in lesions and local T cells of oral lichen planus, especially in non-erosive oral lichen planus, suggesting that ATG9B may be a diagnostic factor for oral lichen planus. Notably, ATG9B-knockdown T cells of oral lichen planus demonstrated autophagy suppression, enhanced proliferation, and attenuated apoptosis, whereas overexpression of ATG9B showed opposite effects on T cells. In the coculture system of T cells and keratinocytes, ATG9B-knockdown T cells of oral lichen planus, but not ATG9B-overexpression T cells, promoted the proliferation and apoptosis of their cocultured keratinocytes. Additionally, exogenous insulin-like growth factor 1 (IGF1) significantly reversed the apoptosis rates of keratinocytes cocultured with T cells expressing abnormal ATG9B. Furthermore, ATG9B-overexpression T cells showed decreased secretion of interferon-γ and tumor necrosis factor-α in the coculture system. ConclusionsThis study revealed the regulatory roles of ATG9B-mediated T-cell autophagy on T-cell immune responses and crosstalk between T cells and keratinocytes in of oral lichen planus.

Detection of anti-desmoglein antibodies in oral lichen planus: What do we know so far.

Oral lichen planus (OLP) is an inflammatory disease of the oral mucosa. Clinically, two main subsets are described, namely non-erosive and erosive OLP. While non-erosive OLP is usually responsive to local therapies, erosive OLP is often refractory also to systemic therapies and extremely reduces the quality of life of the patients. Furthermore, in some erosive OLP cases different autoantibodies have been detected, including anti-desmoglein 1 and 3 autoantibodies, and anti-bullous pemphigoid 180 and 230 autoantibodies. However, their potential role is still not clear. In this paper, we reviewed the literature about the detection of autoantibodies against desmoglein 1 and 3, the main target antigens of pemphigus vulgaris, in patient with OLP, summarizing the more recent insights on this topic.

Photobiomodulation Therapy vs. Corticosteroid for the Management of Erosive/Ulcerative and Painful Oral Lichen Planus. Assessment of Success Rate during One-Year Follow-Up: A Retrospective Study

Photobiomodulation (PBM) therapy is a promising approach for the management of inflammatory conditions and autoimmune lesions, such as oral lichen planus (OLP). The aim of this retrospective study was to assess the effectiveness of PBM in the management of painful and erosive/ulcerative OLP and to compare it with the standard of care that is the topical application of corticosteroids. 96 patients were included with erosive and painful OLP. 48 patients received PBM therapy and 48 received corticosteroids. Data was collected retrospectively on pain using the visual analogue scale; clinical aspects of lesions were assessed with the REU score, and the recurrence rate was noted. One session of PBM therapy with a helium-neon red light (635 nm) was carried out every 48 h for 6 weeks. Treatments were mainly made in contact mode, using a fiber with a diameter of 600 µm (0.6 mm). The output power of the laser beam was calibrated by a power meter. A delivered power of 0.1 W was used for 40 s in a continuous wave (CW), corresponding to a delivered energy of 4 J. The delivered energy density related to the fiber diameter was 1415 J/cm2. Each treated point was considered as 1 cm2 of diameter. PBM therapy within these parameters was carried out on each point until the totality of the lesion was covered, including the non-erosive OLP area. Furthermore, healthy mucosa within 5 mm of the lesion was also irradiated with the same conditions. This PBM treatment was performed during 6 consecutive weeks. The topical corticosteroid treatment consisted of cortisone application to cover the OLP 3 times/day for 6 weeks. Follow-up was made at 6 weeks and at 3, 6 and 12 months. After 6 weeks, both groups showed complete absence of pain, and a complete disappearance of ulcerative/erosive areas. No significant difference was found for both groups concerning the recurrence rate of erosive OLP during the follow-up period; values were 0% at 6 weeks for both groups and 79% and 87.5% for the corticosteroid and PBM group, respectively, at 12 months of follow-up. PBM is effective for managing OLP and is significantly similar to topical corticosteroids without any need for the use of medication and with no reported side effects.

The expression of membrane-bound complement regulatory proteins CD46, CD55 and CD59 in oral lichen planus

ObjectiveTo investigate the expression levels of membrane-anchored complement regulatory proteins (mCRPs), CD46, CD55 and CD59 in oral lichen planus (OLP), and evaluate the activation status of complement. DesignThirty-seven cases of OLP patients (20 non-erosive OLP and 17 erosive OLP) and twenty healthy controls were recruited in this study. The proteins and mRNA expression levels of CD46, CD55 and CD59 in OLP tissues were detected by western blotting and RT-qPCR respectively, and the expression levels of complement C3 and sC5b-9 in OLP patients’ saliva were detected by ELISA to evaluate the activation status of complement. In addition, mucosa tissues of another 3 non-erosive OLP patients and another 3 healthy controls were collected, and the epithelial layer of two groups were separated to culture primary keratinocytes in vitro. Immunofluorescence was used to further detect the expression of mCRPs at the cellular level. ResultsThe levels of CD46, CD55 and CD59 in OLP tissues and cells were significantly decreased compared with those of the healthy control group, and the level of complement C3 in the patients’ saliva was significantly decreased, while the level of sC5b-9 was increased. ConclusionsThese results suggest that the reduced expression of mCRPs keeps the complement system in a continuously active state, which may be the reason of the persistent local immune inflammatory state in OLP. This study aimed to provide new insights for the etiology and therapy of OLP.

Expression of Cathepsin B and Cystatin A in Oral Lichen Planus.

ABSTRACTObjective:Cathepsin B (Cat-B), a cysteine protease, and cystatin A (Cys-A), a protease inhibitor, are involved in the immune response. This study determined Cat-B and Cys-A expression in oral lichen planus (OLP) by immunohistochemistry.Materials and Methods:Thirty specimens each of OLP and healthy gingiva (HG) were included. The expression pattern, the number of positive cells, the staining intensity, and the immunoreactive score (IRS) of Cat-B and Cys-A were investigated. The data were analyzed by using unpaired t-test, Chi-square, and Spearman’s rank correlation.Results:The Cat-B expression in OLP was observed as cytoplasmic staining in the epithelial cells, whereas Cys-A expression was exhibited in the nucleus and cytoplasm of the epithelium. An increase in Cat-B staining intensity was also observed in the basal cells. Conversely, the high staining intensity of Cys-A was observed in the stratum spinosum, but not the stratum basale. In HG, Cat-B expression demonstrated a relatively consistent intensity in the epithelial layer. The Cys-A expression in HG was similar to OLP with a lower staining intensity. The mean percentage of positive cells and the IRS score of Cat-B and Cys-A in OLP were significantly higher than HG (P < 0.05). There was no correlation between Cat-B and Cys-A levels in OLP. Interestingly, Cat-B expression in erosive OLP was greater than in non-erosive OLP (P < 0.05).Conclusion:The Cat-B and Cys-A expression in OLP was more outstanding than in HG, suggesting possible roles for the process of OLP pathogenesis. In addition, Cat-B expression may be an indicator of the disease severity.

Evaluation of the Altered Tissue Expression of HSP60 and HSP70 Genes in Oral and Cutaneous Lichen Planus Compared to Normal Healthy Tissues.

Background:Recent highlights have investigated the possible roles of molecular chaperons like heat shock proteins (HSPs) into Lichen Planus (LP)-onset and pathogenesis. This study for the first, determine the expression of both HSP60 and HSP70 genes in cutaneous LP (CLP) and oral LP (OLP) lesions compared to normal healthy cases and between different subtypes of OLP lesions by real-time (RT)-PCR.Materials and Methods:Paraffin blocks of LP lesions including 56 OLP and 56 CLP samples were selected from theMashhad University of Medical sciences, Mashhad, Iran. Also 56 biopsy samples of healthy normal participants were selected. The demographic and clinical characteristics were extracted from their medical records. The expression of HSP60 and HPS70 genes were evaluated using the real-time RT-PCR method.Results:The comparison of the expression of HSP60 and HSP70 genes among the patients with CLP and OLP showed a significant overexpression of HSP60 and HSP70 genes in both groups compared to the normal participants (P = 0.001). The expression of HSP60 and HSP70 genes was high in both the groups of CLP and OLP patients, but the amount was not significantly different between the two groups. Comparing the two mucosal subgroups of OLP lesions (non-erosive and erosive) showed that the expression of the HSP60 and HSP70 in erosive subtypes of OLP was significantly higher than the non-erosive subtypes of OLP (P = 0.001).Conclusion:Regarding the overexpression of HSP60 and HSP70 in the LP lesions compared to healthy biopsies, we conclude that HSP60 and HSP70 could have key roles in the etiopathogenesis of the OLP and CLP lesions. The overexpression of both HSP60 and HSP70 in the erosive OLP group compared to the non-erosive OLP group emphasized the possible roles of HSPs in the pathogenesis and premalignant changes of OLP lesions.

The expression of Cathepsin L in oral lichen planus

BackgroundMalignant transformation of oral lichen planus (OLP) was reported particularly in erosive type, however, it remains inconclusive. Cathepsin L was shown to promote tumor growth and invasion in many cancers. Therefore, cathepsin L expression in erosive and non-erosive OLP compared with oral epithelial dysplasia and oral squamous cell carcinoma (OSCC) were investigated. MethodsThirty specimens of OLP (15 cases each of erosive and non-erosive OLP), 10 cases of oral epithelial dysplasia and 10 cases of OSCC were included. Ten healthy gingiva specimens were served as controls. All specimens were stained with cathepsin L antibody using immunohistochemistry technique. ResultsCathepsin L was expressed in all OLP and OSCC cases. In oral epithelial dysplasia and healthy gingiva, the expression was found at 90% and 50% respectively. The percentage of positive cells was the highest in erosive OLP (27.26 ± 12.09%), followed by non-erosive OLP (20.85 ± 7.43%), OSCC (20.15 ± 15.70%), oral epithelial dysplasia (9.24 ± 7.00%) and healthy gingiva (2.27 ± 5.65%). Most of non-erosive OLP cases showed mild staining intensity while erosive OLP and OSCC showed moderate staining intensity. Cathepsin L was mainly expressed at basement membrane zone and inflammatory cells of OLP. In OSCC, the expression was found in tumor islands and keratin pearls. In oral epithelial dysplasia and normal gingiva, cathepsin L expressions were low and presented in scattered pattern in both epithelium and connective tissue. ConclusionAccording to the patterns of expression in this study, cathepsin L could be implicated in pathogenesis and severity of OLP.

A pilot study: a possible implication of Candida as an etiologically endogenous pathogen for oral lichen planus

BackgroundThe aim of this study was to investigate the prevalence and genotypic profiles of Candida albicans in patients with oral lichen planus (OLP).Materials and methodsPositive rates and genotypic profiles of Candida albicans strains from OLP patients and healthy controls were analyzed. Random amplified polymorphic DNA and internal transcribed spacer of ribosome DNA polymerase chain reactions were used to sequence the DNA of these strains, and then their genetic similarity was measured using BLAST, UIV Band, and Vector NTI Suite Sequence Analyses Software.ResultsThe prevalence of C. albicans strains detected from erosive-OLP, non-erosive OLP, and normal individuals was 18.87, 18.75, and 7.92%, respectively. Four different genotypes were revealed by the two methods. To be specific, type I was found only in the healthy subjects; type II a and II b were found in non-erosive OLP, and type III was identified in erosive OLP. Intragroup similarity coefficients, i.e. SAB were 100%, and inter-groups similarity coefficients, i.e. SAB were less than 30%.ConclusionsThe genotypic results of C. albicans in OLP revealed an endogenous rather than exogenous infection of C. albicans. In addition, a possible pathogenic role of C. albicans in OLP, with the etiologic sense contributing to a more proper recognition on the pathogenesis, development, and progression of OLP, as well as some strategies for its diagnosis and treatment were identified.

Evaluation of Salivary 8-Isoprostane in Oral Lichen Planus: Case Control Study

Introduction: Lichen planus is a chronic inflammatory disease that affects the skin, nails, and the mucous membrane and oral mucosal involvement may frequently precedes skin manifestation. It is hypothesized that free radicals and reactive oxygen species has a strong relationship in the pathogenesis of oral lichen planus. F2-isoprostane are a group of bioactive prostaglandins and they are isomers of PGF2α is a most accurate approach to assess oxidant injury in vivo. The aim of the study was to evaluate the level of 8-isoprostane in saliva of patients with erosive and nonerosive oral lichen planus in comparison with healthy controls. Materials and Methods: The study participants were selected by convenience sampling from department of oral medicine and dermatology department of our institution. In this case control study, 36 patients with oral lichen planus and 36 control subjects were included. The lichen planus group is again subdivided into erosive and nonerosive lichen planus group. Unstimulated saliva was collected by passive drool method. The salivary 8–isoprostane level was measured by using 8-isoprostane ELISA kit. The statistical tests used were Chi square test, ANOVA and Pearson correlation. Results: The mean values of the salivary 8-isoprostane level an increase in the oral lichen planus group when compared with control group and is statistically significant (P ˂ 0.05). Conclusion: The present study showed that oxidative stress was increased in patients with oral lichen planus, reflected by higher concentration of salivary 8 isoprostane being higher in erosive lichen planus than nonerosive lichen planus.

Estimation of Serum Cortisol Levels in Oral Lichen Planus Patients with Electrochemiluminescence.

Objectives:The objectives of this study were to compare the serum cortisol level in oral lichen planus (OLP) patients with normal healthy individuals and to compare the serum cortisol level in patients with erosive and nonerosive forms of OLP.Materials and Methods:A case–control study involving 60 patients within the age group of 20–50 years was carried out. Group A included 15 subjects with nonerosive lichen planus, without skin involvement; Group B included 15 subjects with erosive lichen planus, without skin; and Group C included 30 subjects with no apparent lesions of the oral mucosa and the skin. From the cases and controls, 7mL venous blood was taken from median cubital vein two times (between 8 and 10 AM, and 4 and 6 PM) by using a 10 mL syringe from which 5 mL was taken for estimation of serum cortisol.Results:The serum cortisol levels of the erosive OLP patients were significantly higher than those of nonerosive OLP patients and controls. There was no significant difference in the serum cortisol levels between nonerosive OLP in comparison with controls.

ASSESSMENT OF SELECT SERUM CYTOKINES TNF-A AND IL-22 IN ORAL LICHEN PLANUS PATIENTS

Introduction Lichen planus (LP) is a chronic inflammatory autoimmune disease that affects oral mucous membranes and skin. Tumor necrosis factor-a (TNF-a) and Interleukin 22 (IL-22) in blood may impact disease progression in oral lichen planus. Methods 97 patients aged 18 to 60 years were studied including 35 with erosive oral lichen planus, 32 with non-erosive oral lichen planus and 30 healthy control subjects of similar age. The levels of serum cytokines TNF-α, IL-22, were determined by enzyme-linked immunosorbent assay (“Immunotech”; France). Results During relapse of erosive oral lichen planus there is change in select cytokines compared with control group levels including IL-22 (36.2±4.1 pg/ml) being 9 - fold increased versus healthy controls (4.2±0.4 pg/ml) and TNF-α being 4.3- fold increased (0.3±1.6 pg/ml versus 1.3±1.2 pg/ml). In erosive chronic OLP there is an increase in IL-22 by 4.5 – fold (18.4±2.2 pg/ml), and an increase of TNF-α by 1.8- fold (0.6±0.4 pg/ml) compared to healthy controls (4.2±0.4 pg/ml and 0.3±1.6 pg/ml, respectively). In chronic non-erosive oral lichen planus IL-22 was reduced 2.1- fold and TNF-α reduced 0.8- fold in comparison to OLP relapse (p Conclusions Acute relapse and chronic stages of lichen planus of the oral mucosa are characterized by immunological changes detectable in peripheral blood serum including increases in TNF-α and IL-22, characteristic of development of a recurrent inflammatory immune response and chronic persistent erosive disease.

Activated Akt/mTOR-autophagy in local T cells of oral lichen planus

Oral lichen planus (OLP) is a chronic inflammatory disease regulated by T cell-mediated immune response. Autophagy and its major inhibitory pathway Akt/mTOR participate in T cell metabolism and homeostasis, which has been implicated in autoimmune diseases. In this study, the potential involvement of autophagy and its regulatory Akt/mTOR pathway were investigated in local T cells of OLP. The expression of Akt/mTOR pathway and autophagy-related proteins in OLP local lesions, as well as in T cells, were measured by immunohistochemistry and double-labeling immunofluorescence, respectively. Furthermore, the associations of p-Akt, p-mTOR, ULK1, and LC3B expression with RAE scores representing the disease severity of OLP were assessed. The expression of p-Akt, p-mTOR, ULK1, and LC3B in OLP lesions, as well as in local T cells, was significantly increased compared with that in controls. In addition, the level of LC3B was negatively correlated with RAE scores of OLP, and LC3B was higher in nonerosive OLP than erosive ones and controls. Our results suggested that activated Akt/mTOR-autophagy may have a role in the local T cell-mediated immunoregulatory mechanism of OLP. LC3B might be a valuable marker to monitor the disease severity of OLP.

Increased circulating CXCR5+ CD4+ T follicular helper-like cells in oral lichen planus.

CD4+ T-helper cell is crucial for the inflammatory autoimmune condition of oral lichen planus (OLP). Recently, the pathogenetic functions of T follicular helper (Tfh) cells, a subtype of CD4+ T-helper cells, have been revealed in autoimmune diseases for their pivotal regulation on humoral immunity. To explore the potential pathophysiological role of Tfh cells in OLP, the expression of circulating Tfh-like cells and its correlations with IL-21 and B cells were investigated. The frequencies of CXCR5+ CD4+ Tfh-like cells and CD19+ B cells were analyzed in peripheral blood of patients with OLP and controls by flow cytometry, respectively. Besides, the serum IL-21 concentration was measured using ELISA technology. Furthermore, the correlations of CXCR5+ CD4+ Tfh-like cells with CD19+ B cells and serum IL-21 expression levels were evaluated. This study showed significant increased circulating Tfh-like cells (P < 0.05) and B cells (P < 0.0001), as well as decreased serum IL-21 expression (P < 0.001) in OLP. Besides, the frequency of Tfh-like cells exhibited negative correlation with B cells in OLP (r = -0.435, P < 0.05). In particular, the proportion of CXCR5+ CD4+ Tfh-like cells in peripheral blood mononuclear cells of erosive OLP was higher than non-erosive OLP and controls (P = 0.012 and 0.021, respectively). Increased circulating Tfh-like cells may be involved in the pathogenesis of OLP through abnormal modulation on B-cell proliferation and IL-21 production, and associated with different clinical forms of OLP.

Association between the clinical severity of oral lichen planus and anti-TPO level in thyroid patients.

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.

Immunohistochemical Evaluation of Ki-67 Expression in Erosive andNon-Erosive Oral Lichen Planus

Background: Oral lichen planus (OLP) is a relatively common, chronic inflammatory condition, which is considered a precancerous lesion. The Ki-67 antigen is expressed in all the phases of the cellular cycle in proliferative cells. Different studies have suggested the relationship between incidences of malignancy in precancerous lesions and the occurrence of this protein. Objectives: This study aimed to evaluate Ki-67 expression in erosive and non-erosive oral lichen planus. Materials and Methods: Specimens (formalin-fixed and paraffin-embedded) of 30 lesions of erosive OLP and 30 lesions of nonerosive OLP were referred for immunehistochemistry (IHC) analysis of Ki-67. Results of immunohistochemistry were statistically evaluated by means of the chi-square test and independent t-test. The level of statistical significance was established at P < 0.05. Results: The mean expression of Ki-67 in patients with erosive OLP was higher than people in the control group. These differences were statistically significant (P = 0.041). Conclusions: Since Ki-67 is extensively accepted as an important biomarker in diagnosis, prognosis and treatment of cancerous and precancerous lesions, a high degree of presence of this biomarker in chronic precancerous lesions, such as erosive OLP, can be of great use in prognosis and suggested treatments.