Function of unconventional T cells in oral lichen planus revealed by single-cell RNA sequencing.

OBJECTIVE: We intended to map the single-cell profile of OLP, explore the molecular characteristics of unconventional T cells in OLP tissues. METHODS: Buccal mucosa samples from OLP patients and healthy individuals were used to prepare single-cell suspension. Single-cell RNA sequencing was used to analyze the proportion of all the cells, and the molecular characteristics of unconventional T cells. Immunohistochemical staining was used to detect the expression of unconventional T cells marker genes. RESULTS: The cell clusters from buccal mucosa were categorized into immune cells, fibroblasts, endothelial cells, and epithelial cells. Unconventional T cells with phenotype of CD247+TRDC+NCAM1+ were identified. Immunohistochemical staining revealed higher expression of unconventional T cell marker genes in OLP tissue, predominantly in the lamina propria. In OLP, unconventional T cells are in a unique stress response state, exhibited enhanced NF-κB signaling and apoptosis inhibition, enhanced heat shock protein genes expression, weakened cytotoxic function. A large number of ligand-receptor pairs were found between unconventional T cells and other cells, particularly with fibroblasts and endothelial cells. CONCLUSIONS: This study mapped the single-cell profile of OLP, delineated the molecular characteristics of unconventional T cells in OLP, and uncovered that these unconventional T cells are in a stress response state.

CD4+CD8αα+ is the dominant phenotype of intraepithelial lymphocytes and regulated by ThPOK and Runx3 in oral lichen planus.

BACKGROUND: Oral lichen planus (OLP) is a common T cell-mediated oral mucosal immune inflammatory disease. Intraepithelial lymphocytes (IELs) are a unique subset of T cells that play an important role in regulating immune response. This study aims to investigate the phenotype and the differentiation mechanism of IELs in OLP. METHODS: The expression of CD4, CD8α, CD8ß, T-helper-inducing POZ/Krueppel-like factor (ThPOK), and RUNX family transcription factor 3 (Runx3) in the epithelium and peripheral blood mononuclear cells (PBMCs) of OLP was determined by immunofluorescence and immunohistochemistry. Then, the correlations among them were analyzed. Naïve CD4+ T cells were sorted from blood of OLP patients and stimulated with retinoic acid (RA) and transforming growth factor-ß1 (TGF-ß1). Then the expression of CD4, CD8α, CD8ß, ThPOK, and Runx3 was investigated by immunocytochemistry. RESULTS: CD8α expression and CD8αα+ cells were upregulated in the epithelium of OLP, whereas they were downregulated in PBMCs of OLP. CD8ß was not expressed in the epithelium of OLP. CD4, CD8α, and Runx3 expression and CD4+CD8α+ cells were increased, whereas ThPOK expression was decreased in the epithelium of OLP. CD8α expression was positively correlated with Runx3 expression, whereas ThPOK expression was negatively correlated with Runx3 expression. After RA and TGF-ß1 stimulation, CD8α and Runx3 expression was upregulated, and ThPOK expression was downregulated in naïve CD4+ T cells. CONCLUSION: CD4+CD8αα+ IELs may be the dominant phenotype of IELs in OLP, and the differentiation of CD4+CD8αα+ IELs in OLP is negatively regulated by ThPOK and positively regulated by Runx3.

Increased pathogenicity and pro-inflammatory capabilities of mucosal-associated invariant T cells involved in Oral Lichen Planus.

BACKGROUND: Mucosal-associated invariant T (MAIT) cells assume pivotal roles in numerous autoimmune inflammatory maladies. However, scant knowledge exists regarding their involvement in the pathological progression of oral lichen planus (OLP). The focus of our study was to explore whether MAIT cells were altered across distinct clinical types of OLP. METHODS: The frequency, phenotype, and partial functions of MAIT cells were performed by flow cytometry, using peripheral blood from 18 adults with non-erosive OLP and 22 adults with erosive OLP compared with 15 healthy adults. We also studied the changes in MAIT cells in 15 OLP patients receiving and 10 not receiving corticosteroids. Surface proteins including CD4, CD8, CD69, CD103, CD38, HLA-DR, Tim-3, Programmed Death Molecule-1 (PD-1), and related factors released by MAIT cells such as Granzyme B (GzB), interferon (IFN)-γ, tumour necrosis factor (TNF)-α, interleukin (IL)-17A, and IL-22 were detected. RESULTS: Within non-erosive OLP patients, MAIT cells manifested an activated phenotype, evident in an elevated frequency of CD69+ CD38+ MAIT cells (p < 0.01). Conversely, erosive OLP patients displayed an activation and depletion phenotype in MAIT cells, typified by elevated CD69 (p < 0.01), CD103 (p < 0.05), and PD-1 expression (p < 0.01). Additionally, MAIT cells exhibited heightened cytokine production, encompassing GzB, IFN-γ, and IL-17A in erosive OLP patients. Notably, the proportion of CD103+ MAIT cells (p < 0.05) and GzB secretion (p < 0.01) by MAIT cells diminished, while the proportion of CD8+ MAIT cells (p < 0.05) rose in OLP patients with corticosteroid therapy. CONCLUSIONS: MAIT cells exhibit increased pathogenicity and pro-inflammatory capabilities in OLP. Corticosteroid therapy influences the expression of certain phenotypes and functions of MAIT cells in the peripheral blood of OLP patients.

Circulating mucosal-associated invariant T cell alterations in adults with recent-onset and long-term oral lichen planus.

BACKGROUND: Mucosal-associated invariant T (MAIT) cells play key roles in many inflammatory diseases. However, their effects on the long-term course of oral lichen planus (OLP) and recent-onset OLP remain unclear. In this study, we aimed to investigate the function of MAIT cells in the different processes of OLP and to explore the immunological background of this disease. METHODS: The frequency, phenotype, cytokine secretion, and clinical relevance of MAIT cells were investigated. MAIT cells were collected from the peripheral blood of 14 adults with recent-onset OLP (7-120 days after disease onset) and 16 adults with long-term course OLP (>2 years after diagnosis) using flow cytometry and compared with 15 healthy blood donors. Statistical analyses were performed using the GraphPad Prism software. RESULTS: MAIT cells from adults with recent-onset OLP exhibited an activated phenotype, as indicated by an increased frequency of CD69+ (p < 0.05) and CD38+MAIT cells (p < 0.01) and elevated production of the proinflammatory cytokine IL-17 A (p < 0.01), compared with healthy adult donors. In adults with long-term OLP, MAIT cells exhibited an activated and exhausted phenotype, characterized by high expression of CD69 (p < 0.01) and PD-1 (p < 0.001) and increased production of granzyme B released (p < 0.01). Compared with recent-onset OLP patients, long-term OLP patients showed a decreased production of CD8+, and CD4-CD8- cells, but an increase in PD-1+ production (p < 0.05). CONCLUSIONS: Circulating MAIT cells exhibited activation in OLP patients across varying disease durations. Given that PD-1 expression is elevated in adults with long-term OLP, it is reasonable to infer that circulating MAIT cells in long-term OLP may exhibit a more exhausted state than those in recent-onset OLP.

Oral lichen planus: a microbiologist point of view.

Oral lichen planus (OLP) is a chronic disease of uncertain etiology, although it is generally considered as an immune-mediated disease that affects the mucous membranes and even the skin and nails. Over the years, this disease was attributed to a variety of causes, including different types of microorganisms. This review analyzes the present state of the art of the disease, from a microbiological point of view, while considering whether or not the possibility of a microbial origin for the disease can be supported. From the evidence presented here, OLP should be considered an immunological disease, as it was initially proposed, as opposed to an illness of microbiological origin. The different microorganisms so far described as putative disease-causing agents do not fulfill Koch's postulates; they are, actually, not the cause, but a result of the disease that provides the right circumstances for microbial colonization. This means that, at this stage, and unless new data becomes available, no microorganism can be envisaged as the causative agent of lichen planus.

Omega-3 polyunsaturated fatty acids: a promising approach for the management of oral lichen planus.

BACKGROUND: Oral lichen planus (OLP) is a T-cell-mediated inflammatory disease with a risk of malignant transformation. Although the etiology of OLP is still uncertain, growing evidence suggests that oral microbiota, antigen-specific, and non-specific mechanisms are involved in the pathogenesis of OLP. Antigen-specific mechanisms include antigen presentation, T-cell activation, nuclear factor-kappa B signaling pathway, and cytokine secretion, while non-specific mechanisms consist of matrix metalloproteinases (MMP)-9 upregulation, psychological pressure, oxidative damage, aberrant expression of microRNAs (miRNAs), and autophagy. Till now, there is no cure for OLP, and the main purpose of OLP therapy is symptomatic control. FINDING: Seafood and its derivative omega-3 polyunsaturated fatty acids (n-3 PUFAs) can suppress antigen presentation, T-cell activation, and nuclear factor-kappa B signaling pathway, modulate the overexpressed inflammatory cytokines, inhibit the expression of MMP-9, as well as regulate the expression of miRNAs and autophagy. And they are possible agents for ameliorating psychological disorder and oxidative damage. Moreover, n-3 PUFAs supplementation has a beneficial effect on preventing tumorigenesis. CONCLUSION: n-3 PUFAs consumption may provide a non-toxic, inexpensive administration for OLP.

Potential roles of the CCL17-CCR4 axis in immunopathogenesis of oral lichen planus.

BACKGROUND: Oral lichen planus (OLP) is a T cell-mediated chronic inflammatory disease. C-C chemokine receptor type 4 (CCR4) and its cognate C-C motif chemokine ligand 17 (CCL17) play a key role in T-cell activation and trafficking, but their implication in OLP pathogenesis has not been explored. Our study was designed to analyze the expression and function of the CCL17-CCR4 axis in OLP. METHODS: The mRNA expression levels of CCL17 and CCR4 in the circulating T cells of OLP subjects were examined by quantitative real-time PCR. The protein levels of CCL17 and CCR4 in the peripheral blood of OLP subjects were detected by enzyme-linked immunosorbent assay (ELISA) and Simple Western assay, respectively. The functional relevance of increased expression of CCL17 and CCR4 in OLP was demonstrated in proliferation, apoptosis, and migration assays. RESULTS: The mRNA and protein expression levels of CCL17 and CCR4 in the peripheral blood of patients with OLP were significantly upregulated compared with those of controls. CCL17 induced the migration of OLP T cells. In addition, blocking CCR4 with a small molecule CCR4 antagonist not only inhibited the proliferation and migration of OLP T cells but also promoted the apoptosis of OLP T cells. CONCLUSION: Our findings indicate that the CCL17-CCR4 axis might be responsible for the inflammatory infiltration of T cells in OLP.

Enhanced T-cell proliferation and IL-6 secretion mediated by overexpression of TRIM21 in oral lesions of patients with oral lichen planus.

BACKGROUNDS: To explore the expression and functions of the tripartite motif-containing protein 21 (TRIM21) in oral lichen planus(OLP) lesions. METHODS: Paraffin sections of buccal mucosa samples from 15 cases of reticular oral lichen planus (OLP) patients and 10 healthy controls were used for immunohistochemistry to determine expression and distribution of TRIM21. Buccal mucosae from 11 OLP patients and seven healthy controls were analyzed by qPCR to quantify its gene expression. Peripheral blood mononuclear cells and CD3+ cells from four pairs of age- and sex-matched OLP patients and healthy controls were isolated for immunocytochemistry and culture. Following lentivirus-mediated overexpression of TRIM21 gene in CD3+ cells, CCK-8 was applied to evaluate cell proliferation. Cytokines including IL-2, IL-4, IL-5, IL-6, IL-10, TNF-α, and IFN-γ in the supernatants were measured by the cytometric bead array and verified by ELISA. RESULTS: A larger number of TRIM21-positive cells infiltrating the lamina propria were observed in OLP lesions by immunohistochemistry than those of healthy controls. Significantly higher transcription of TRIM21 was revealed by qPCR. TRIM21 overexpression in CD3+ cells significantly enhanced the proliferation and IL-6 secretion in CD3+ cells from 12 to 72 hours. CONCLUSION: Overexpressed TRIM21 in OLP may be a primary proinflammatory molecule rather than a secondary and inducible regulatory factor in immunopathogenesis of OLP.

Possible Mechanisms Involved in the Cooccurrence of Oral Lichen Planus and Hashimoto's Thyroiditis.

Oral lichen planus (OLP) is a chronic inflammatory oral mucosal disorder mediated by T cells, with a multifactorial etiology. Hashimoto's thyroiditis (HT) is a common autoimmune disease characterized by hypothyroidism. Although many clinical studies conducted over the past several decades have reported the cooccurrence of OLP and HT, the underlying mechanism remains unclear. This review summarizes potential mechanisms that might be involved in the cooccurrence of OLP and HT. We find that OLP and HT share a common or overlapping pathogenesis in terms of immune, heredity, environmental, and hormonal factors, which might cause cooccurrence. Furthermore, considering the latency of HT, a routine screen for thyroid diseases, particularly HT, is suggested for confirmed OLP patients.

Immunological methods for the diagnosis of oral mucosal diseases.

Immunological methods, which have been widely used in autoimmune blistering diseases (AIBDs) of the oral mucosa, can also be adopted as auxiliary diagnostic tools in oral lichen planus (OLP) and discoid lupus erythematosus (DLE). AIBDs, characterized by autoantibodies against structural proteins of keratinocytes or the basement membrane zone, clinically present as blisters and erosions of the oral mucosa. When atypical lesions occur, OLP or DLE may be confused with AIBDs. The improvement of diagnostic accuracy is necessary due to the significant differences in treatment and prognosis among these diseases. A variety of immunological methods are used for qualitative and quantitative detection of target antigens and autoantibodies. These methods can evaluate efficacy of treatment, monitor diseases and guide treatment decisions. In this review, we discuss the application of immunofluorescence, biochemical tests, and protein microarrays for AIBDs, OLP and DLE, as well as the differential diagnostic methods using immunological tests.

Artemisinin and its derivatives: a potential therapeutic approach for oral lichen planus.

BACKGROUND: Oral lichen planus (OLP) is a common T-cell-mediated oral mucosal disease, whose pathogenesis mainly includes antigen-specific and non-specific mechanisms. As a refractory chronic inflammatory disease, there is still no curable management for OLP till now. FINDINGS: Artemisinins are a family of compounds that are widely used as frontline treatment for malaria worldwide. In addition to its well-established antimalarial properties, emerging evidence hints that artemisinin family drugs also possess preferential immunoregulatory and anti-inflammation properties, such as modifying T lymphocytes' activation and cytokines release, modulating Th1/Th2 balance, activating regulatory T cells (Tregs), modulating inflammatory signaling pathways, as well as acting on non-specific mechanisms of OLP. However, there is still no report focused on the influence of artemisinins on OLP. CONCLUSION: This review outlined the data-based immunomodulatory effects of artemisinins on different immune cells in conjunction with their therapeutic prospective with regard to the pathogenesis of OLP, suggesting that artemisinin and its derivatives might be possible candidates for treatment of OLP.

Circulating exosomes regulate T-cell-mediated inflammatory response in oral lichen planus.

BACKGROUND: Exosomes are newly recognized natural nanocarrier and intercellular messenger that emerge as important mediators of signal transmission. Exosomes have been reported to modulate the inflammatory response of a number of diseases. This study investigated the effects of circulating exosomes from oral lichen planus (OLP) on T cells. METHODS: Plasma-derived exosomes were purified from both OLP patients and control groups. T cells were observed under a confocal laser scanning microscope after co-cultivation with PKH67 labeled exosomes for 12, 24, and 48 hours. The effects of exosomes exposure on T cells were analyzed with several functional assays, investigating proliferation, apoptosis, and migration. Production of interleukin (IL)-2, -4, -10, and interferon (IFN)-γ was measured via enzyme-linked immunosorbent assay. RESULTS: PKH67-labeled exosomes were taken up by T cells in a time- and dose-dependent manner. Several biological functions of T cells were promoted. In particular, the circulating erosive OLP exosomes significantly enhanced T-cell proliferation and attenuated the apoptosis. The migration capacity of T cells increased remarkably in response to erosive OLP exosome treatment. In addition, the ratio of IFN-γ/IL-4 was significantly elevated in OLP patients. CONCLUSIONS: Our findings indicate that the circulating OLP exosomes are involved in the biological functions of T cells, potentially promoting the OLP progression by regulating the T-cell-mediated inflammatory response.

Aberrant histone modification and inflammatory cytokine production of peripheral CD4+ T cells in patients with oral lichen planus.

BACKGROUNDS: To investigate alterations in histone modification and histone deacetylases (HDACs) in patients with oral lichen planus (OLP), and to evaluate correlations with inflammatory cytokine production. METHODS: Global histone H3/H4 acetylation and HDAC activity in CD4+ T cells from 23 patients with OLP and 10 healthy control subjects were examined using spectrophotometry. The mRNA levels of eight members of four classes of HDAC genes were measured by real-time quantitative polymerase chain reaction. Forty cytokines involved in inflammation were examined with a cytokine array. The correlation between histone modification and cytokine production was analyzed. RESULTS: Global histone H3 hypo-acetylation was observed in OLP patients. Patients with OLP had significantly higher HDACs activity,and higher HDAC6 and HDAC7 mRNA level compared with the controls. Of the 40 cytokines in the cytokine array, eight were significantly increased in OLP patients: interleukin (IL)-4, IL-8, IL-1ra, tumor necrosis factor receptor II (TNFR II), macrophage inflammatory protein 1b (MIP-1b), fibrosis-associated tissue inhibitors of metalloproteinase 1 (TIMP)-1, monocyte chemotactic protein 1 (MCP-1), and eotaxin-2. In the OLP group, the acetylation level of histone H3 was negatively correlated with IL-4 and MCP-1 production, and the expression of HDAC6 mRNA was positively correlated with MCP-1 production. In the non-erosive subgroup, acetylation of histone H3 was negatively correlated with IL-4, IL-16, and TIMP-2 production. In the erosive OLP subgroup, the expression of HDAC7 mRNA was positively correlated with MIP-1a production. CONCLUSION: Aberrant histone modification of CD4+ T cells in peripheral blood could occur in OLP patients, and possibly affects inflammatory cytokine production.

New evidence of connections between increased O-GlcNAcylation and inflammasome in the oral mucosa of patients with oral lichen planus.

Oral lichen planus (OLP) is considered a chronic inflammatory immune-mediated disease of the oral mucosa. Immunopathogenesis of OLP is thought to be associated with cell-mediated immune dysregulation. O-GlcNAcylation is a form of reversible glycosylation. It has been demonstrated that O-GlcNAcylation promoted nuclear factor kappa B (NF-κB) signalling. Activation of NF-кB can induce expression of nucleotide-binding domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, which is a large intracellular multi-protein complex involving an immune response. Dysregulated expression of the NLRP3 inflammasome was reported to be associated with autoinflammatory diseases. No integrative studies between O-GlcNAcylation and NLRP3 inflammasome in OLP patients have been reported. The present study aimed to determine the immunohistochemical expression of O-GlcNAcylation, NF-κB signalling molecules and NLRP3 inflammasome in oral mucosae of OLP patients. Oral tissue samples were collected from 30 OLP patients and 30 healthy individuals. Immunohistochemical staining and analyses of immunostaining scores were performed to evaluate expression of O-GlcNAcylation, NF-κB signalling molecules and NLRP3 inflammasome. According to observations in this study, significantly higher levels of O-GlcNAcylation, NF-κB signalling molecules and NLRP3 inflammasome were demonstrated in OLP patients compared with control subjects (P < 0·001). Positive correlations among O-GlcNAcylation, NF-κB signalling molecules and NLRP3 inflammasome were also observed in OLP samples (P < 0·01). In conclusion, the present study provides supportive evidence that increased O-GlcNAcylation is associated with increased expression of NLRP3 inflammasome via the NF-κB signalling pathway. These findings provide a new perspective on immunopathogenesis of OLP in relation to autoinflammation.

The association and potentially destructive role of Th9/IL-9 is synergistic with Th17 cells by elevating MMP9 production in local lesions of oral lichen planus.

BACKGROUND: This study was to investigate association and potentially destructive role of Th9/IL-9 and their synergistic interaction with Th17 cells in elevating MMP9 production in local lesions of oral lichen planus (OLP) patients. METHODS: Oral mucosal tissues were obtained from OLP patients and healthy controls (HC) and then divided into an epithelial part (EP) or a lamina propria part (LP). Both EP and LP subsets were assessed for IL-9 and MMP9 mRNA levels by real-time quantitative PCR (qPCR). Flow cytometry was used to detect the CD4+ T helper subset Th9 (IL-9+ IL-17- CD4+ ) and Th17 (IL-9- IL-17+ CD4+ ) in co-cultured CD4+ Th cells and oral keratinocytes of OLP. IL-9, IL-17, and MMP9 in co-culture supernatant were detected by ELISA. RESULTS: The qPCR results demonstrated that IL-9 and MMP9 mRNA levels were positively correlated in OLP lesions, and both significantly elevated in EP and LP lesions of erosive type OLP. Th9 and Th17 cells were significantly elevated in co-cultures of CD4+ Th cells and keratinocytes, and MMP9, IL-9, and IL-17 levels were simultaneously increased. In vitro, recombinant human IL-17 treatment significantly enhanced MMP9 protein and mRNA levels, while a synergistic effect of IL-9 and IL-17 was not observed. However, further results showed Th17 cells, IL-17, and MMP9 were increased significantly when recombinant IL-9 was added to the cultured CD4+ T cells. CONCLUSION: This study demonstrated that Th9/IL-9 can induce elevated levels of MMP9 to aggravate OLP disease severity, which may occur directly through increasing Th17 levels or indirectly through a synergistic role with Th17.

DNA methylation patterns of genes related to immune response in the different clinical forms of oral lichen planus.

BACKGROUND: The oral lichen planus is a chronic inflammatory disease. Although its aetiology is not well understood, the role of T lymphocytes in its inflammatory events is recognised. Identifying the epigenetic mechanisms involved in the pathogenesis of this immune-mediated condition is fundamental for understanding the inflammatory reaction that occurs in the disease. The purpose of this work was to evaluate the methylation pattern of 21 immune response-related genes in the different clinical forms of oral lichen planus. METHODS: A cross-sectional study was performed to analyse the DNA methylation patterns in three distinct groups of oral lichen planus: (i) reticular/plaque lesions; (ii) erosive lesions; (iii) normal oral mucosa (control group). After DNA extraction from biopsies, the samples were submitted to digestions by methylation-sensitive and methylation-dependent enzymes and double digestion. The relative percentage of methylated DNA for each gene was provided using real-time polymerase chain reaction arrays. RESULTS: Hypermethylation of the STAT5A gene was observed only in the control group (59.0%). A higher hypermethylation of the ELANE gene was found in reticular/plaque lesions (72.1%) compared to the erosive lesions (50.0%). CONCLUSION: Our results show variations in the methylation profile of immune response-related genes, according to the clinical type of oral lichen planus after comparing with the normal oral mucosa. Further studies are necessary to validate these findings using gene expression analysis.

A mechanistic linkage between oral lichen planus and autoimmune thyroid disease.

OBJECTIVE: To determine the levels of antithyroid antibodies and thyroid hormones in the sera of patients with oral lichen planus (OLP), and to quantify the expression of thyroid proteins in OLP lesions. SUBJECTS AND METHODS: Venous blood samples were drawn from 110 patients with OLP who had no history of thyroid disease or levothyroxine supplementation (OLP+/LT4 -). A random population sample of 657 healthy subjects was used as the control group. Two additional groups were used as comparators. Immunohistochemical and qPCR analyses were performed on tissue specimens collected from the patients with OLP and thyroid disease and healthy subjects. RESULTS: No association was found between the presence of antithyroid antibodies and OLP. More patients in the OLP+/LT4 - group showed high levels of thyroid-stimulating hormone and low levels of free thyroxine than were seen in the control group. Thyroid-stimulating hormone receptor was more highly expressed in the OLP lesions of patients with thyroid disease than in the healthy oral mucosa. CONCLUSIONS: A significant number of patients with OLP who are not previously diagnosed with thyroid disease have thyroid parameters that are compatible with hypothyroidism. The expression of thyroid-stimulating hormone receptor in OLP lesions suggests that mechanisms related to autoimmune thyroid disease are involved in the aetiology of OLP.

Hematinic deficiencies and anemia statuses in anti-gastric parietal cell antibody-positive or all autoantibodies-negative erosive oral lichen planus patients.

BACKGROUND/PURPOSE: Approximately 27% of erosive oral lichen planus (EOLP) patients have serum anti-gastric parietal cell antibody (GPCA) positivity. This study assessed whether serum GPCA or EOLP itself was a significant factor that caused hematinic deficiencies and anemia statuses in GPCA-positive or autoantibodies-negative EOLP patients (GPCA+/EOLP and Abs-/EOLP patients). METHODS: The mean corpuscular volume (MCV) and mean blood hemoglobin (Hb), iron, vitamin B12, and folic acid levels were measured and compared between any two of three groups of 41 GPCA+/EOLP patients, 198 Abs-/EOLP patients, and 184 healthy control subjects. RESULTS: GPCA+/EOLP patients had significantly lower mean Hb, iron (for women only), and vitamin B12 level as well as significantly greater frequencies of Hb, iron, and vitamin B12 deficiencies than healthy control subjects. Moreover, GPCA+/EOLP patients had significantly lower serum vitamin B12 level and significantly higher MCV as well as a significantly greater frequency of vitamin B12 deficiency than Abs-/EOLP patients. Furthermore, Abs-/EOLP patients did have significantly lower mean Hb, MCV, iron (for women only), vitamin B12, and folic acid levels as well as significantly greater frequencies of Hb and iron deficiencies than healthy control subjects. CONCLUSION: We conclude that serum GPCA is the major factor that causes vitamin B12 deficiency, macrocytosis and pernicious anemia in GPCA+/EOLP patients. Approximately 29-32% GPCA-positive EOLP patients have vitamin B12 deficiency or macrocytosis and about 23-25% vitamin B12 deficiency or macrocytosis EOLP patients have pernicious anemia. ELOP itself does play a significant role in causing anemia and hematinic deficiencies in Abs-/EOLP patients.

Serum and Salivary IgA, IgG, and IgM Levels in Oral Lichen Planus: A Systematic Review and Meta-Analysis of Case-Control Studies.

Immunoglobulins (IgA, IgG, and IgM) are significant anti-inflammatory factors. The meta-analysis aimed to assess the serum and salivary levels of Igs as more important immunoglobulins in patients affected by oral lichen planus (OLP) compared to the healthy controls. Four databases, including PubMed/Medline, Scopus, Web of Science, and Cochrane Library as well as Iranian databases were checked up to January 2018 without language restriction. The quality of each involved study was done using the Newcastle⁻Ottawa Quality Assessment Scale (NOS) questionnaire. A random-effects model analysis was done by RevMan 5.3 software applying the mean difference (MD) plus 95% confidence intervals (CIs). The CMA 2.0 software was applied to calculate the publication bias among the studies. Out of 70 studies found in the databases, 8 studies were involved and analyzed in the meta-analysis. The meta-analysis included 282 OLP patients and 221 healthy controls. The pooled MDs of serum levels of IgA, IgG, and IgM were -0.13 g/L [95% CI: -0.24, -0.02; P = 0.02], 1.01 g/L [95% CI: -0.91, 2.93; P = 0.30], and -0.06 g/L [95% CI: -0.25, 0.14; P = 0.56], respectively; whereas, the salivary IgA and IgG levels were 71.54 mg/L [95% CI: 12.01, 131.07; P = 0.02] and 0.59 mg/L [95% CI: -0.20, 1.38; P = 0.14], respectively. Considering the few studies performed on saliva, the results suggested that the salivary levels, especially IgA level had higher values than the serum levels. Therefore, the salivary immunoglobulins can play a significant function in the OLP pathogenesis.

Evaluation of Serum Desmoglein 1 and Desmoglein 3 in Oral Erosive Lichen Planus before and after Topical Application of Tacrolimus.

AIM: The current study will attempt to throw light on the role of desmoglein 1 and desmoglein 3 in the pathogenesis of erosive lichen planus and their response to topical application of tacrolimus. MATERIALS AND METHODS: Twenty patients with erosive oral lichen planus received tacrolimus ointment three times daily for eight weeks. Assessments using the clinical score and a visual analog scale were recorded at each visit. Serum concentrations of circulating autoantibodies to desmoglein 1 and desmoglein 3 will be determined by enzyme-linked immunosorbent assay (ELISA) at baseline, four weeks and eight weeks after treatment. Statistical software SPSS v.17.0 was used for statistical analysis. RESULTS: All patients showed significant improvement in all outcomes within the follow-up periods when compared with the baseline (p < 0.05). The mean value of the visual analog scale were 8.30 ± 1.49, 4.15 ± 1.14, 2.10 ± 0.91, 0.90 ± 0.79, and 0.0 ± 0.0 starting from baseline to the end of follow up period. The mean value of the clinical score were 4.7 ± 0.48, 2.9 ± 1.29, 1.8 ± 1.32, 1.31 ± 0.69, and 0.69 ± 0.09 starting from baseline to the end of follow-up period. There was a significant decrease in the levels of anti-Dsg1 and anti-Dsg3, during the follow-up period (p < 0.05). CONCLUSION: The concluded data suggest that antibodies against desmoglein 1 and desmoglein 3 seem to play a key role in the pathogenesis of oral lichen planus. Also, there is a significant decrease in the level of anti-Dsgl and anti-Dsg3 autoantibodies with topical tacrolimus 0.1% ointment. CLINICAL SIGNIFICANCE: Monitoring the serum level of antibodies against keratinocyte cadherins Dsg 1 and Dsg 3 can be used to evaluate the effect of topical application of tacrolimus on Erosive Oral lichen planus.