Th1/Th2 Cytokine Ratio in Tissue Transudates from Patients with Oral Lichen Planus

Objective. The characteristics of oral lichen planus (OLP) provoke investigators to explore possible biomarkers by which to monitor disease activity and therapeutic efficacy. Oral fluids may provide an accessible medium for analysis of such biomarkers. Previous studies have shown that activation of nuclear factor-kappa B (NF-κ B) plays an important role in the pathogenesis of oral lichen planus (OLP), which is a chronic inflammatory disorder mediated by T cells. Prior to the present investigation, reports of the levels of NF-κ B and its dependent cytokines in oral fluids have not been forthcoming. The purpose of this study was to detect the level of NF-κ B dependent cytokines, TNF-alpha, IL-1-alpha, IL-6, and IL-8 in tissue transudates directly from lesions of OLP, and explore the feasibility of the data for clinical application. Study design. Thirteen definitively diagnosed OLP subjects were enrolled in the study as were 13 age-sex matched controls. In each subject, lesion tissue transudates (TTs) were collected by a novel collection technique with a filter paper. The level of cytokines, TNF-alpha, IL-1-alpha, IL-6, and IL-8 in three types of oral fluids were determined by ELISA. Results. In the tissue transudate(TT), there were significantly higher level of cytokines TNF-alpha, IL-1-alpha, IL-6, and IL-8 detected in OLP patients than in controls: (TT: 40.0 ± 9.8 versus 4.5 ± 0.7, 710 ± 114 versus 305 ± 78, 150 ± 25 versus 1.7 ± 0.5, 2800 ± 260 versus 1450 ± 130, P < .0001; unit: pg/mL). Conclusions. These results indicate that NF-κ B dependent inflammatory cytokines may be detected at increased levels in oral lesion tissue transudates which may have diagnostic and prognostic potentials for monitoring disease activity and making therapeutic decisions in patients with OLP

Effect of Tobacco Smoking on the Clinical, Histopathological, and Serological Manifestations of Sjögren’s Syndrome

Objectives To assess the association of smoking habits with the clinical, serological, and histopathological manifestations of Sjögren’s syndrome (SS) and non-Sjögren’s sicca (non-SS sicca). Methods Cross-sectional case-control study of 1288 patients with sicca symptoms (587 SS and 701 non-SS sicca) evaluated in a multi-disciplinary research clinic. Smoking patterns were obtained from questionnaire data and disease-related clinical and laboratory data were compared between current, past, ever, and never smokers. Results Current smoking rates were 4.6% for SS patients compared to 14.1% in non-SS sicca (p = 5.17x10E-09), 18% in a local lupus cohort (p = 1.13x10E-14) and 16.8% in the community (p = 4.12x10E-15). Current smoking was protective against SS classification (OR 0.35, 95%CI 0.22–0.56, FDR q = 1.9E10-05), focal lymphocytic sialadenitis (OR 0.26, 95%CI 0.15–0.44, FDR q = 1.52x10E-06), focus score ≥1 (OR 0.22, 95%CI 0.13–0.39, FDR q = 1.43x10E-07), and anti-Ro/SSA(+) (OR 0.36, 95%CI 0.2–0.64, FDR q = 0.0009); ever smoking was protective against the same features and against anti-La/SSB(+) (OR 0.52, 95%CI 0.39–0.70, FDR q = 5.82x10E-05). Duration of smoking was inversely correlated with SS even after controlling for socioeconomic status, BMI, alcohol and caffeine consumption. Conclusions Current tobacco smoking is negatively and independently associated with SS, protecting against disease-associated humoral and cellular autoimmunity. The overall smoking rate amongst SS patients is significantly lower than in matched populations and the effects of smoking are proportional to exposure duration. In spite of the protective effects of tobacco on SS manifestations, it is associated with other serious comorbidities such as lung disease, cardiovascular risk and malignancy, and should thus be strongly discouraged in patients with sicca

Quantitative Proteomics Reveals Myosin and Actin as Promising Saliva Biomarkers for Distinguishing Pre-Malignant and Malignant Oral Lesions

Oral cancer survival rates increase significantly when it is detected and treated early. Unfortunately, clinicians now lack tests which easily and reliably distinguish pre-malignant oral lesions from those already transitioned to malignancy. A test for proteins, ones found in non-invasively-collected whole saliva and whose abundances distinguish these lesion types, would meet this critical need.To discover such proteins, in a first-of-its-kind study we used advanced mass spectrometry-based quantitative proteomics analysis of the pooled soluble fraction of whole saliva from four subjects with pre-malignant lesions and four with malignant lesions. We prioritized candidate biomarkers via bioinformatics and validated selected proteins by western blotting. Bioinformatic analysis of differentially abundant proteins and initial western blotting revealed increased abundance of myosin and actin in patients with malignant lesions. We validated those results by additional western blotting of individual whole saliva samples from twelve other subjects with pre-malignant oral lesions and twelve with malignant oral lesions. Sensitivity/specificity values for distinguishing between different lesion types were 100%/75% (p = 0.002) for actin, and 67%/83% (p<0.00001) for myosin in soluble saliva. Exfoliated epithelial cells from subjects' saliva also showed increased myosin and actin abundance in those with malignant lesions, linking our observations in soluble saliva to abundance differences between pre-malignant and malignant cells.Salivary actin and myosin abundances distinguish oral lesion types with sensitivity and specificity rivaling other non-invasive oral cancer tests. Our findings provide a promising starting point for the development of non-invasive and inexpensive salivary tests to reliably detect oral cancer early

Variants at multiple loci implicated in both innate and adaptive immune responses are associated with Sjögren’s syndrome

Sjögren’s syndrome is a common autoimmune disease (~0.7% of European Americans) typically presenting as keratoconjunctivitis sicca and xerostomia. In addition to strong association within the HLA region at 6p21 (Pmeta=7.65×10−114), we establish associations with IRF5-TNPO3 (Pmeta=2.73×10−19), STAT4 (Pmeta=6.80×10−15), IL12A (Pmeta =1.17×10−10), FAM167A-BLK (Pmeta=4.97×10−10), DDX6-CXCR5 (Pmeta=1.10×10−8), and TNIP1 (Pmeta=3.30×10−8). Suggestive associations with Pmeta<5×10−5 were observed with 29 regions including TNFAIP3, PTTG1, PRDM1, DGKQ, FCGR2A, IRAK1BP1, ITSN2, and PHIP amongst others. These results highlight the importance of genes involved in both innate and adaptive immunity in Sjögren’s syndrome

Rare X chromosome abnormalities in systemic lupus erythematosus and Sjögren's syndrome

Objective: Sjögren's syndrome (SS) and systemic lupus erythematosus (SLE) are related by clinical and serologic manifestations as well as genetic risks. Both diseases are more commonly found in women than in men, at a ratio of ~10 to 1. Common X chromosome aneuploidies, 47,XXY and 47,XXX, are enriched among men and women, respectively, in either disease, suggesting a dose effect on the X chromosome. Methods: We examined cohorts of SS and SLE patients by constructing intensity plots of X chromosome single-nucleotide polymorphism alleles, along with determining the karyotype of selected patients. Results: Among ~2,500 women with SLE, we found 3 patients with a triple mosaic, consisting of 45,X/46,XX/47,XXX. Among ~2,100 women with SS, 1 patient had 45,X/46,XX/47,XXX, with a triplication of the distal p arm of the X chromosome in the 47,XXX cells. Neither the triple mosaic nor the partial triplication was found among the controls. In another SS cohort, we found a mother/daughter pair with partial triplication of this same region of the X chromosome. The triple mosaic occurs in ~1 in 25,000–50,000 live female births, while partial triplications are even rarer. Conclusion: Very rare X chromosome abnormalities are present among patients with either SS or SLE and may inform the location of a gene(s) that mediates an X dose effect, as well as critical cell types in which such an effect is operative. © 2017, American College of Rheumatolog

Effect of Tobacco Smoking on The Clinical, Histopathological, and Serological Manifestations of Sjögren’s Syndrome

The authors wish to thank Dr. A. Darise Farris for her critical review of the cellular immune response discussion.Objectives To assess the association of smoking habits with the clinical, serological, and histopathological manifestations of Sjögren’s syndrome (SS) and non-Sjögren’s sicca (non-SS sicca). Methods Cross-sectional case-control study of 1288 patients with sicca symptoms (587 SS and 701 non-SS sicca) evaluated in a multi-disciplinary research clinic. Smoking patterns were obtained from questionnaire data and disease-related clinical and laboratory data were compared between current, past, ever, and never smokers. Results Current smoking rates were 4.6% for SS patients compared to 14.1% in non-SS sicca (p = 5.17x10E-09), 18% in a local lupus cohort (p = 1.13x10E-14) and 16.8% in the community (p = 4.12x10E-15). Current smoking was protective against SS classification (OR 0.35, 95%CI 0.22–0.56, FDR q = 1.9E10-05), focal lymphocytic sialadenitis (OR 0.26, 95%CI 0.15–0.44, FDR q = 1.52x10E-06), focus score ≥1 (OR 0.22, 95%CI 0.13–0.39, FDR q = 1.43x10E-07), and anti-Ro/SSA(+) (OR 0.36, 95%CI 0.2–0.64, FDR q = 0.0009); ever smoking was protective against the same features and against anti-La/SSB(+) (OR 0.52, 95%CI 0.39–0.70, FDR q = 5.82x10E-05). Duration of smoking was inversely correlated with SS even after controlling for socioeconomic status, BMI, alcohol and caffeine consumption. Conclusions Current tobacco smoking is negatively and independently associated with SS, protecting against disease-associated humoral and cellular autoimmunity. The overall smoking rate amongst SS patients is significantly lower than in matched populations and the effects of smoking are proportional to exposure duration. In spite of the protective effects of tobacco on SS manifestations, it is associated with other serious comorbidities such as lung disease, cardiovascular risk and malignancy, and should thus be strongly discouraged in patients with sicca.Yeshttp://www.plosone.org/static/editorial#pee

The New Specialties of Orofacial Pain and Oral Medicine: Practical Strategies to Improve Access to Care for Orofacial Disorders

ABSTRACTOrofacial disorders are common and complex disorders with an estimated collective prevalence of over 40% of the general population. To improve access to care, orofacial pain and oral medicine have now been recognized as dental specialties. Thus, it is recommended that all dental schools and other health professional schools increase pre- and post-doctoral education, patient care, clinical training, and research on these conditions. This paper reviews the barriers and solutions to improving access to quality, effective, and affordable care for oral and facial disorders to prevent complications, chronic pain and the negative impact on the lives of those who suffer from them

Burning Mouth (Syndrome) Disorder

Burning mouth disorder (BMD) is a chronic, oral pain condition associated with burning sensations of the tongue, lips, and mucosal regions of the mouth. Diagnosis of the condition is complicated by the fact that a variety of systemic and local factors can be contributory. Treatment goals are to reduce symptoms by eliminating identifiable abnormalities. Secondary lines of therapy include pharmacotherapeutic approaches that target neuropathologic mechanisms that appear to be active