Non-erosive Patients Research Articles

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

BackgroundMucosal-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.MethodsThe 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.ResultsWithin 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.ConclusionsMAIT 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.

Evaluation of circulating microRNA signature in patients with erosive hand osteoarthritis: The HOAmiR study

ObjectivesTo identify circulating micro-RNAs differentially expressed in patients with erosive hand osteoarthritis (HOA) compared to patients with non-erosive HOA and patients without HOA. MethodsIn the screening phase, 768 well-characterized micro-RNAs using Taqman Low Density Array cards were measured in 30 sera from 10 patients with erosive HOA, 10 patients with non-erosive HOA and 10 controls without HOA, matched for age and BMI. In a second step, we validated the micro-RNAs identified at the screening phase (adjusted p value < 0.05 after false discovery rate correction using Benjamini-Hochberg method and literature review) in larger samples (60 patients with erosive HOA and 60 patients without HOA matched for age and BMI). ResultsIn the screening phase, we identified 21 down-regulated and 4 up-regulated micro-RNAs of interest between erosive HOA and control groups. Among these, 9 micro-RNAs (miR-373-3p, miR-558, miR-607, miR-653-5p, miR-137 and miR448 were down-regulated and miR-142-3p, miR-144-3p and miR-34a-5p were up-regulated) were previously described in chondrocytes homeostasis or OA. We found only one significantly down-regulated micro-RNA between erosive and non-erosive HOA. In the validation phase, we showed replication of a single micro-RNA the significant downregulation of miR-196-5p, that had been previously identified in the screening phase among patients with erosive HOA compared to those without HOA.After reviewing the literature and the miRNA-gene interaction prediction model, we found that this microRNA could interact with bone homeostasis and HOXC8, which could explain its role in osteoarthritis. ConclusionsWe found that miR-196-5p was down regulated in patients with erosive HOA and some of its targets could explain a role in OA.

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.

Exploring the clinical relevance of "Angico Gum": an effective biopolymer for topical protection of oesophageal mucosa in gastroesophageal reflux disease patients.

Angico gum (AG) (Anadenanthera colubrina var. Cebil [Griseb.] Altschul) is utilized by some Brazilian communities to alleviate symptoms from gastroesophageal reflux disease. Here, we aimed to investigate the "in vitro" topical protective capacity of AG on human esophageal mucosa. Biopsies of the distal esophageal mucosa were collected from 35 patients with heartburn (24 non-erosive and 11 with erosive oesophagitis (EE)) and mounted in Üssing chambers. AG was applied topically, followed by exposure with acid solution (pH 2.0 or pH 1.0), where transepithelial electrical resistance (TER) and The transepithelial permeability for fluorescein was assessed. The incubation of the AG labeled with FITC in the esophageal mucosa was localized by fluorescence microscopy. Pretreatment with AG prevented the drop in TER induced by acid solution, as well as significantly decreases the fluorescein permeability in non-erosive patients. The protective effect of AG was sustained for up to 120 min both in biopsies of non-erosive and erosive esophagitis. Confocal microscope images showed mucosal luminal adherence of FITC-labeled AG. AG had a prolonged topical protective effect against acid solution in mucosal biopsies of patients with non-erosive and erosive esophagitis.

Efficacy of the Traditional Chinese Medicine, Qingganhewei Decoction, in Treating Refractory Non-Erosive Reflux Patients with Stagnated Heat in the Liver and Stomach: a Study Protocol for a Prospective Randomized Double-Blind Clinical Trial

Efficacy of the Traditional Chinese Medicine, Qingganhewei Decoction, in Treating Refractory Non-Erosive Reflux Patients with Stagnated Heat in the Liver and Stomach: a Study Protocol for a Prospective Randomized Double-Blind Clinical Trial

Revisiting the Role of Esophageal Mucosal Dilated Intercellular Spaces in the Diagnosis and Pathophysiology of Heartburn.

Dilated intercellular spaces (DISs) facilitate the diffusion of noxious agents into the deep layers of the esophageal epithelium. The role of DIS in heartburn pathogenesis is still controversial. Therefore, we aim to reinvestigate DIS in an extensively evaluated group of patients and healthy controls (HCs). We classified 149 subjects into the following groups: 15 HC, 58 mild erosive reflux disease (ERD), 17 severe ERD, 25 nonerosive reflux disease (NERD), 15 reflux hypersensitivity (RH), and 19 functional heartburn (FH). A total of 100 length measurements were performed for each patient's biopsy. The overall intercellular spaces (ISs) value of gastroesophageal reflux disease (GERD) patients was higher than that of HC (P = 0.020). In phenotypes, mild ERD (vs HC [P = 0.036], NERD [P = 0.004], RH [P = 0.014]) and severe ERD (vs HC [P = 0.002], NERD [P < 0.001], RH [P = 0.001], FH [P = 0.004]) showed significantly higher IS. There was no significant difference between the HC, NERD, RH, and FH groups. The 1.12 μm DIS cutoff value had 63.5% sensitivity and 66.7% specificity in the diagnosis of GERD. There was a weak correlation (r = 0.302) between the IS value and acid exposure time, and a weak correlation (r = -0.359) between the IS value and baseline impedance. A strong correlation was shown between acid exposure time and baseline impedance (r = -0.783). Since the IS length measurement had better discrimination power only in erosive groups, it is not feasible to use in daily routine to discriminate other nonerosive phenotypes and FH. The role of DIS in heartburn in nonerosive patients should be reconsidered.

Distal Mean Nocturnal Baseline Impedance Predicts Pathological Reflux of Isolated Laryngopharyngeal Reflux Symptoms

Diagnosis of isolated laryngopharyngeal reflux symptoms (ILPRS), ie, without concomitant typical reflux symptoms (CTRS), remains difficult. Mean nocturnal baseline impedance (MNBI) reflects impaired mucosal integrity. We determined whether esophageal MNBI could predict pathological esophagopharyngeal reflux (pH+) in patients with ILPRS. In this cross-sectional study conducted in Taiwan, non-erosive or low-grade esophagitis patients with predominant laryngopharyngeal reflux symptoms underwent combined hypopharyngeal multichannel intraluminal impedance-pH monitoring when off acid suppressants. Participants were divided into the ILPRS (n = 94) and CTRS (n = 63) groups. Asymptomatic subjects without esophagitis (n = 25) served as healthy controls. The MNBI values at 3 cm and 5 cm above the lower esophageal sphincter (LES) and the proximal esophagus were measured. Distal but not proximal esophageal median MNBI values were significantly lower in patients with pH+ than in those with pH- (ILPRS in pH+ vs pH-: 1607 Ω vs 2709 Ω and 1885 Ω vs 2563 Ω at 3 cm and 5 cm above LES, respectively; CTRS in pH+ vs pH-: 1476 vs 2307 Ω and 1500 vs 2301 Ω at 3 cm and 5 cm above LES, respectively, P < 0.05 for all). No significant differences of any MNBI exist between any pH- subgroups and healthy controls. The areas under the receiver operating characteristic curve in the ILPRS group were 0.75 and 0.80, compared to the pH- subgroup and healthy controls (P < 0.001 for both), respectively. Interobserver reproducibility was good (Spearman correlation 0.93, P < 0.0001). Distal esophageal MNBI predicts pathological reflux in patients with ILPRS.

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.

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.

Chemokine and Cytokine Profiles in Patients with Hand Osteoarthritis.

Background: The development of hand osteoarthritis (HOA) and its progression into the erosive subset are unclear, but inflammation is suspected to be the main source. To verify the involvement of inflammation in HOA pathogenesis, we evaluate serum inflammatory mediators and their association with HOA-related clinical features in patients. Methods: 153 participants (50 non-erosive HOA patients, 54 erosive HOA patients, and 49 healthy control subjects) were included in this study. All patients underwent clinical examination, which included assessment of tender and swollen small hand joints, ultrasound (US) examination, and self-reported measures (e.g., AUSCAN or algofunctional indexes). Serum inflammatory mediators were quantified using human cytokine 27-plex immunoassay. We employed linear modelling, correlation analysis, and resampling statistics to evaluate the association of these mediators to HOA. Results: We identified increased levels of nine inflammatory mediators (e.g., eotaxin, monocyte chemoattractant protein 1, interleukin-8, and tumour necrosis factor) in HOA patients compared to healthy controls. Increased mediators correlated with ultrasound findings as well as with clinically tender and swollen joint counts in patients with erosive HOA. However, none of the mediators distinguished between erosive and non-erosive HOA subtypes. Conclusion: Our findings support the hypothesis on the involvement of inflammation in HOA.

THU0081 MIR-17-5P REDUCES INFLAMMATION AND BONE EROSIONS IN COLLAGEN INDUCED ARTHRITIS MICE AND DIRECTLY TARGETS THE JAK-STAT PATHWAY IN RHEUMATOID ARTHRITIS FIBROBLAST-LIKE SYNOVIOCYTES.

Background:micro-RNAs (miR) are strong regulators of gene expression. Their involvement in RA key cytokines pathway regulation entitles them as important players in RA pathophysiology. The miR 17-92 cluster has been widely studied in cancer as they regulate cell apoptosis.Objectives:The aims of this study were to screen miR 17-92 cluster’s expression in different RA phenotypes (erosive and non erosive), further elucidate the mechanisms and direct targets involved in miR-17-5p anti-inflammatory role and to investigate miR-17-5p therapeutic effect in arthritis.Methods:A miR array was performed in synovial tissue from naïve erosive and non-erosive RA patients. Intra-articular delivery of miR-17 lipoplex was performed in collagen induced arthritis model in mice. Clinical, histological and structural effects were studied over the course of arthritis. In depth studies of miR-17 mechanisms of action were performed in primary RA-FLS isolated from RA synovial tissue.Results:Among others, miR-17-5p expression was reduced in erosive RA. miR-17 transfection in arthritic paws significantly reduced clinical inflammation. Moreover, synovial B cells, T cells, macrophages and polynuclear neutrophils infiltrates were significantly reduced. Structural damage was also decreased as shown by a reduction in the number of osteoclasts and erosion score by CT analysis. Pro-inflammatory cytokines of the IL-6 family, STAT3 target genes and IL-1β expression were also significantly reduced, but not TNF-alpha. miR17 directly targeted the 3’-untranslated region of STAT3 and JAK1. STAT3 and JAK1 mRNA and protein expression were reduced in RA-FLS following miR-17 transfection. STAT3 and JAK1 mRNA and activation of STAT3 as assessed by immunohistochemistry were also reduced in injected paws.Conclusion:We demonstrate an anti-inflammatory and anti-erosive role of miR-17 in vivo. This effect involves the suppression of the IL-6 family autocrine amplifying loop through the direct targeting of JAK1 and STAT3 as shown in RA-FLS.FigureEffect of miR-17 lipoplex injection in Collagen induced arthritis (CIA) mice’s ankles.Disclosure of Interests:None declared

Two forms of one complication: Late erosive and nonerosive postpancreatectomy hemorrhage following laparoscopic pancreaticoduodenectomy.

Postpancreatectomy hemorrhage (PPH) remains a rare but lethal complication following laparoscopic pancreaticoduodenectomy (LPD) in the modern era of advanced surgical techniques. The main reason for early PPH (within 24 hours following surgery) has been found to be a failure of hemostasis during the surgical procedure. The reasons for late PPH tend to be variate. Positive associations have been identified between late PPH and intraabdominal erosive factors such as postoperative pancreatic fistula, bile leakage, gastrointestinal fistula, and intraabdominal infection. Still, some patients suffer PPH who do not have these erosive factors. The severity of bleeding and clinical prognosis of erosive and nonerosive PPH following LPD is different.We analyzed the electronic clinical records of 33 consecutive patients undergoing LPD and experiencing one or more episodes of hemorrhage after postoperative day 1 in this study. All patients received an LPD with standard lymphadenectomy. The patient's hemorrhage-related information was extracted, such as interval from surgery to bleeding, presentation, bleeding site, severity, management, and clinical prognosis. Based on our clinical practice, we proposed a treatment strategy for these 2 forms of late PPH following LPD.Of these 33 patients, 8 patients (24.24%) developed nonerosive bleeding, and other 25 patients (75.76%) suffered from postoperative hemorrhage caused by various intraabdominal erosive factors. The median interval from the LPD surgery to postoperative hemorrhage for both groups was 11 days, and no significant differences were found (P = .387). For patients with erosive bleeding, most (60%) underwent their episodes of bleeding on postoperative days 5 to 14. For patients with nonerosive bleeding, most (75%) began postoperative hemorrhage 2 weeks after surgery, and 50% of these patients had bleeding between postoperative days 20 and 30. In the present study, 64% (16/25) of patients with erosive bleeding and 87.5% (7/8) of patients with nonerosive bleeding had internal bleeding. The fact that 90% (9/10) of all gastrointestinal bleeding patients had intraabdominal erosive factors indicated strong relationships between gastrointestinal hemorrhage and these erosive factors. The bleeding sites were detected in most patients, except for 4 patients who received conservative treatments. For patients with erosive bleeding, the most common bleeding site detected was the pancreatic remnant (43.48%); others included the hepatic artery (39.13%), splenic artery (13.04%), and left gastric artery (4.35%). For patients with nonerosive bleeding, the most common bleeding site was the hepatic artery (83.33%), and the 2nd most frequent site was the splenic artery (16.67%). No hemorrhage from pancreaticojejunal anastomosis occurred in the patients with nonerosive bleeding. Statistical significance was noted between these 2 groups in hemorrhage severity (P = .012), management strategies (P = .001), rebleeding occurrence (P = .031), and prognosis outcome (P = .010). The patients with intraabdominal erosive factors tended to have a higher risk of grade C bleeding (68.00%) than that of their nonerosive bleeding counterparts (12.50%). As for treatment strategy for postoperative bleeding, the favorable method to manage nonerosive bleeding was conservative and endovascular treatments if the patients’ hemodynamics was stable. All these nonerosive bleeding patients survived. On the contrary, 22 patients (88.00%) in the erosive bleeding group had a 2nd surgical procedure, and the mortality was 56.00%. In this group, 2 patients received conservative therapy due to the demand of their family and expired. One patient underwent endovascular treatment and had another episode of hemorrhage, finally dying from multi-organ failure. No patients in the nonerosive bleeding group suffered from rebleeding after complete hemostasis, and 44.00% of patients with erosive bleeding underwent a 2nd episode of postoperative bleeding.Erosive and nonerosive PPH are 2 forms of this lethal complication following LPD. Their severity of bleeding, rebleeding rate, and treatment strategy are different. Patients with erosive factors tend to have a higher incidence of grade C bleeding, rebleeding, and mortality. Factors influencing treatment protocols for PPH include the existence of intraabdominal erosive factors, patient hemodynamics, possibility to detect the bleeding site during endovascular treatment, and surgeon's preference. The performance of endovascular treatment with stent repair for managing postoperative hemorrhage after LPD depends on the discovery of the bleeding site. Surgery should be reserved as an emergent and final choice to manage PPH.

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.

Esophageal baseline impedance levels allow the identification of esophageal involvement in patients with systemic sclerosis.

Distal esophageal baseline impedance (BI) levels reflect the esophageal mucosal integrity in reflux disease. Systemic sclerosis (SSc) could potentially affect the integrity of esophageal mucosa and consequently impair distal and proximal BI levels, but data in this regard are lacking. We aimed to prospectively investigate and compare BI levels among non-erosive reflux disease (NERD), SSc patients, and healthy controls (HCs). Consecutive patients with reflux symptoms and well-defined diagnosis of SSc underwent upper endoscopy and, in case of no lesions encountered, manometry and impedance-pH testing off-therapy. In addition to traditional impedance-pH parameters, BI values at 3, 5, 7, and 17cm above the lower esophageal sphincter were calculated. Fifty-two patients with NERD, 50 with SSc, and 50 HCs were enrolled. Nineteen (38%) SSc patients and 22 (42%) NERD patients had abnormal acid exposure. In patients with SSc, median BI values were significantly lower than in NERD patients and HCs (p < 0.0001) at 3, 5, and 7cm; there was no difference between HCs and NERD patients at 17cm in the proximal esophagus, whereas a significant difference was observed at 17cm between SSc and NERD as well as HCs (p < 0.01). Distal and proximal BI values in SSc patients were lower than in NERD and HCs, thus we speculated that these findings may be related to the deposition of collagen in the connective tissue. Measurement of BI may be used as an indirect, but simple and accurate marker of esophageal involvement in patients with SSc.

Altered Autophagy-Associated Genes Expression in T Cells of Oral Lichen Planus Correlated with Clinical Features

Oral lichen planus (OLP) is a T cell-mediated inflammatory autoimmune disease. Autophagy has emerged as a fundamental trafficking event in mediating T cell response, which plays crucial roles in innate and adaptive immunity. The present study mainly investigated the mRNA expression of autophagy-associated genes in peripheral blood T cells of OLP patients and evaluated correlations between their expression and the clinical features of OLP. Five differentially expressed autophagy-associated genes were identified by autophagy array. Quantitative real-time RT-PCR results confirmed that IGF1 expression in the peripheral blood T cells of OLP patients was significantly higher than that in controls, especially in female and middle-aged (30–50 years old) OLP patients. In addition, ATG9B mRNA levels were significantly lower in nonerosive OLP patients. However, no significant differences were found in the expression of HGS, ESR1, and SNCA between OLP patients and controls. Taken together, dysregulation of T cell autophagy may be involved in immune response of OLP and may be correlated with clinical patterns.

Association of joint erosion with SLC22A4 gene polymorphisms inconsistently associated with rheumatoid arthritis susceptibility

Two single-nucleotide polymorphisms (SNPs) in SLC22A4 encoding an organic cation/zwitterion transporter protein, rs2073838 (commonly called slc2F1) and rs3792876 (slc2F2), had been associated with susceptibility to rheumatoid arthritis (RA) in two Japanese and one recent Chinese studies but not in other two Japanese and six Caucasian studies. In this study, the two SNPs were genotyped for 2313 Korean participants and their associations with RA susceptibility and severity were examined. SNP association with RA susceptibility was tested among 1304 RA patients and 1009 healthy controls, and association with joint erosion among 1063 erosive and 241 non-erosive RA patients. Meta-analysis for RA susceptibility association was additionally performed using 10 previous studies and the current one. The two SNPs were almost perfectly correlated with each other (r2 = 0.98), and therefore only slc2F1 was tested for association. RA susceptibility association was not found in Koreans (p = 0.93), but still significant in meta-analysis of six Asian studies including this Korean study (p = 0.00036, odds ratio = 1.1) or all 11 studies additionally including five Caucasian studies (p = 0.00021, odds ratio = 1.1). In contrast, an association was found for RA severity in Koreans. The minor allele A was marginally associated with 1.5-fold increased risk of joint erosion among RA patients afflicted for ≤11 years (p = 0.025) or ≤7 years (p = 0.029), though not among patients with longer-standing RA. Accordingly, SLC22A4 was associated with joint erosion in not-very-longstanding RA, although RA susceptibility association was weak and its clinical significance was uncertain.

Evaluation of the Relationship between Serum Lipid Profile andOral Lichen Planus.

Background and aims. Oral lichen planus (OLP) is an immunologic disorder. A large number of studies have reported that lipid rafts have a key role in receptor signaling of lymphocytes. Here, we explore the potential of lipid rafts as targets for the development of a new class of agents to down-modulate immune responses and treat autoimmune diseases.Materials and methods. The present cross-sectional study evaluated 88 patients referring to the Department of Oral Medicine in 3 groups (Group 1: erosive OLP; Group 2: non-erosive OLP; Group 3: healthy). A total of 3 mL of blood sample was taken from each subject and the serum levels of cholesterol, triglycerides, HDL and LDL were determined. The mean outcomes of each group were compared with each other and analyzed two by two.Results. The results of statistical analyses showed no significant differences in mean HDL and LDL serum levels between the three groups. The results of post hoc LSD test showed that mean serum levels of subjects with erosive and non-erosive lichen planus were higher than those in healthy subjects. In relation to triglyceride serum levels, the mean serum levels of triglycerides were higher in erosive and non-erosive OLP patients compared to healthy subjects.Conclusion. Triglyceride and cholesterol can be considered to have a critical role in the incidence of lichen planus and in its manifestations as predisposing factors.

AB0260 Dynamic Serum Matrix Metalloproteinase-3 as A Diagnostic Biomarker of Erosive Disease and Radiographic Progression in Rheumatoid Arthritis

BackgroundRheumatoid arthritis (RA) is an autoimmune disease characterized by chronic synovitis, resulting in joint destruction and disability. Matrix metalloproteinase (MMP) 3 plays essential role in the degradation of extracellular components...

Association Between Non-erosive Reflux Disease and High Risk of Obstructive Sleep Apnea in Korean Population.

Background/AimsObstructive sleep apnea is becoming more important in gastroesophageal reflux disease (GERD) patients. This study investigated the prevalence of high risk for obstructive sleep apnea in GERD patients in comparison with that in healthy controls using the Berlin Questionnaire. We also investigated the risk factors for obstructive sleep apnea in GERD patients.MethodsWe enrolled 1,007 subjects: 776 healthy controls, 115 individuals with erosive reflux disease, and 116 with non-erosive reflux disease. GERD was diagnosed and classified using endoscopy and a reflux questionnaire. The Berlin Questionnaire was used to evaluate obstructive sleep apnea.ResultsMore patients in the GERD group (28.2%) had higher risk for obstructive sleep apnea than healthy controls (20.4%, P = 0.036). More patients with non-erosive disease (32.8%) had higher risk for obstructive sleep apnea (OSA) than patients with erosive disease (20.9%) and controls (20.4%, P = 0.010). On multivariate analysis, non-erosive disease was a high risk factor for obstructive sleep apnea (odds ratio [OR], 1.82; P = 0.011). Age ≥ 55 years (OR, 1.83; P < 0.001) and a high body mass index (≥ 25 kg/m2) (OR, 2.76; P < 0.001) were also identified as risk factors. Nocturnal GERD was related to high risk for OSA in non-erosive disease patients (OR, 2.97; P = 0.019), but not in erosive disease patients.ConclusionsHigh risk for OSA is more prevalent in GERD patients than in controls. Non-erosive reflux disease, age ≥ 55, and a high BMI are associated with high risk for OSA.

Role of Ultrastructural Alterations of Intercellular Junction and Tight-junction Proteins in Patients With Gastroesophageal Reflux Disease

TO THE EDITOR: I read with great interest the study by Liu et al 1 regarding the significant correlation between presence of desmosomal junction alterations and the severity of gastroesophageal reflux disease (GERD). The authors reported that tight-junction proteins (TJP) such as claudin-1 and claudin-2 were abundant not only in asymptomatic controls but also in patients with gastroesophageal reflux disease and, a significant intercellular space (ICS) dilatation occurred only in upper stratified squamous epithelium of patients with moderate erosive esophagitis, while there was no difference in ICS dilatation of lower basal cuboidal epithelium among different groups of patients with GERD and controls. Furthermore, this study revealed that alterations in desmosomal junctions and their processes under transmission electron microscopy increased in parallel with the severity of GERD. Esohageal mucosal ICS were frequently seen with nonerosive reflux disease (NERD) and patients with esophagitis. 2 In addition, dilatation of intercellular spaces was an early marker of damage caused by gastroesophageal reflux, and treatment of proton pump inhibitor led to a complete recovery of dilated intercellular spaces in 97.4%. 3 Although the authors showed an important results of ultrastructural alterations of esophageal mucosa in patients with GERD, there were a few limitations most of which had been discussed in this paper. First, in contrast to this study, previous studies demonstrated that dilated ICS was associated with NERD and erosive GERD. For instance, Caviglia et al 4 reported that mean ICS diameter in NERD patients was 3 times greater than in controls. Moreover, Zhong et al 5 reported that reflux esophagitis (RE) patients showed wider ICS (1.29 μm [1.10-1.46 μm], n = 6) than NERD patients (1.10 μm [0.95-1.21 μm], n = 16) and controls (1.01 μm [0.94-1.17 μm], n = 12). Differences in the study population and definition of GERD severity may contribute to this discrepancy. In this study, authors defined mild RE in case of Los Angeles classification A (LA-A) esophagitis and moderate RE in case of LA-B esohagitis, but there were no patients with LA-C or LA-D eosphagitis. However, Zhong et al 5 classified LA-A/B into mild RE and LA-C/D into severe RE. I wonder whether the severe GERD patients including LA-C/D may have influence on the results or not, but there was no explanation regarding this matter in the discussion. Second, the authors showed that there were no differences in the presence of claudin-1 and claudin-2 expression among patients with GERD, NERD and controls. However, previous study revealed that claudin-1 expression in RE and NERD patients were significantly higher than in the control. Moreover, expression of occludin tended to be lower in the RE patients and the expression of claudin-3 tended to be higher in the RE and NERD patients, however, none of these were statistically significant. 3 These findings suggested the role of several other TJP including several types of claudins, occludins and junctional adhesion molecules, as authors have mentioned in the discussion. Despite these limitations of the present study, it provides us with the important information in the ultrastructural alterations of ICS and TJP in the inflamed esophageal mucosa. Further studies are needed to validate the results of the present study.