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Clinical and Experimental Rheumatology Dec 2022Ultrasound is a promising diagnostic method when it comes to assessing the involvement of major salivary glands in patients with primary Sjögren's syndrome (pSS). A... (Review)
Review
Ultrasound is a promising diagnostic method when it comes to assessing the involvement of major salivary glands in patients with primary Sjögren's syndrome (pSS). A matter of debate is whether ultrasound of the major salivary glands (SGUS) can replace a salivary gland biopsy in the diagnosis or classification of pSS. The intra- and inter-observer reliability of SGUS was found to be good, especially when focusing on hypoechogenic areas and homogeneity, and comparable to the reliability of histopathologic characteristics of salivary gland biopsies of pSS patients. However, replacing salivary gland biopsy by SGUS led to substantial decrease of the accuracy of the 2016 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria with clinical diagnosis as the gold standard. When SGUS was added as an additional item to the criteria, the accuracy of the criteria remained high, offering at the same time the clinicians a wider array of tools to assess patients. Combination of SGUS and anti-SSA antibodies was shown to be highly predictive of the classification of a patient suspected of pSS, making routine salivary gland biopsy debatable.
Topics: Humans; Sjogren's Syndrome; Reproducibility of Results; Salivary Glands; Ultrasonography; Biopsy
PubMed: 36305349
DOI: 10.55563/clinexprheumatol/xbcu8d -
Journal of Leukocyte Biology Jan 2024Sjögren's syndrome is a systemic autoimmune disease characterized by dysfunction of the affected exocrine glands. Lymphocytic infiltration within the inflamed glands... (Review)
Review
Sjögren's syndrome is a systemic autoimmune disease characterized by dysfunction of the affected exocrine glands. Lymphocytic infiltration within the inflamed glands and aberrant B-cell hyperactivation are the two salient pathologic features in Sjögren's syndrome. Increasing evidence indicates that salivary gland epithelial cells act as a key regulator in the pathogenesis of Sjögren's syndrome, as revealed by the dysregulated innate immune signaling pathways in salivary gland epithelium and increased expression of various proinflammatory molecules as well as their interaction with immune cells. In addition, salivary gland epithelial cells can regulate adaptive immune responses as nonprofessional antigen-presenting cells and promote the activation and differentiation of infiltrated immune cells. Moreover, the local inflammatory milieu can modulate the survival of salivary gland epithelial cells, leading to enhanced apoptosis and pyroptosis with the release of intracellular autoantigens, which further contributes to SG autoimmune inflammation and tissue destruction in Sjögren's syndrome. Herein, we reviewed recent advances in elucidating the role of salivary gland epithelial cells in the pathogenesis of Sjögren's syndrome, which may provide rationales for potential therapeutic targeting of salivary gland epithelial cells to alleviate salivary gland dysfunction alongside treatments with immunosuppressive reagents in Sjögren's syndrome.
Topics: Humans; Sjogren's Syndrome; Salivary Glands; Epithelial Cells; Epithelium; Inflammation
PubMed: 37134025
DOI: 10.1093/jleuko/qiad049 -
PET Clinics Apr 2022Salivary gland tumors (SGTs) are a heterogeneous group of neoplasms arising from the 3 pairs of major salivary glands (parotid, submandibular, and sublingual) or... (Review)
Review
Salivary gland tumors (SGTs) are a heterogeneous group of neoplasms arising from the 3 pairs of major salivary glands (parotid, submandibular, and sublingual) or numerous minor salivary glands located throughout the oral cavity. This review discusses the role of PET/computed tomography (CT) in evaluation of SGTs, including staging, restaging, prognostication, and response assessment. 18F-fluorodeoxyglucose (FDG) PET/CT is useful for staging and restaging malignant SGTs and offers important prognostic information in these patients. It is less useful for differentiating benign and malignant SGTs. Non-FDG PET radiotracers, perineural spread, parotid incidentalomas, and interpretative pitfalls are discussed as well.
Topics: Fluorodeoxyglucose F18; Humans; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Salivary Gland Neoplasms; Salivary Glands; Tomography, X-Ray Computed
PubMed: 35232668
DOI: 10.1016/j.cpet.2021.12.002 -
Current Protocols in Immunology Dec 2020Sjögren's syndrome (SS) is a systemic autoimmune disease affecting multiple organ systems. Salivary and lacrimal gland involvement cause dry mouth and dry eye and are...
Sjögren's syndrome (SS) is a systemic autoimmune disease affecting multiple organ systems. Salivary and lacrimal gland involvement cause dry mouth and dry eye and are the most common clinical presentations of the disease. Patients with SS also have autoantibodies targeting multiple nuclear and cytoplasmic antigens. Innate immune activation plays a critical role in SS pathogenesis. This article describes the activation of specific innate immune pathways in mice to study SS salivary gland manifestations. Methodologies for evaluating salivary gland inflammation and salivary function are described. This article also describes protocols for in-house assays to measure autoantibody titers in serum. © 2020 Wiley Periodicals LLC Basic Protocol 1: Acceleration of Sjögren's syndrome by activating the toll-like receptor 3 pathway Basic Protocol 2: Induction of Sjögren's syndrome by activating the stimulator of interferon genes pathway Alternate Protocol: Acceleration of Sjögren's syndrome by the administration of Freund's incomplete adjuvant Support Protocol 1: Evaluating salivary gland function Support Protocol 2: Evaluating salivary gland inflammation Support Protocol 3: Measuring autoantibody titers by indirect immunofluorescence.
Topics: Animals; Cell Culture Techniques; Humans; Immunity, Innate; Inflammation; Interferons; Mice; Models, Animal; Salivary Glands; Sjogren's Syndrome
PubMed: 33252847
DOI: 10.1002/cpim.114 -
Medicina Clinica Jan 2021
Topics: Humans; Salivary Gland Diseases; Salivary Gland Neoplasms; Salivary Glands; Ultrasonography
PubMed: 32739098
DOI: 10.1016/j.medcli.2020.03.010 -
Oral Diseases Jan 2024Tight junctions (TJs) are cell-cell interactions that localize at the most apical portion of epithelial/endothelial cells. One of the predominant functions of TJs is to... (Review)
Review
Tight junctions (TJs) are cell-cell interactions that localize at the most apical portion of epithelial/endothelial cells. One of the predominant functions of TJs is to regulate material transport through paracellular pathway, which serves as a selective barrier. In recent years, the expression and function of TJs in salivary glands has attracted great interest. The characteristics of multiple salivary gland TJ proteins have been identified. During salivation, the activation of muscarinic acetylcholine receptor and transient receptor potential vanilloid subtype 1, as well as other stimuli, promote the opening of acinar TJs by inducing internalization of TJs, thereby contributing to increased paracellular permeability. Besides, endothelial TJs are also redistributed with leakage of blood vessels in cholinergic-stimulated submandibular glands. Furthermore, under pathological conditions, such as Sjögren's syndrome, diabetes mellitus, immunoglobulin G4-related sialadenitis, and autotransplantation, the integrity and barrier function of TJ complex are impaired and may contribute to hyposalivation. Moreover, in submandibular glands of Sjögren's syndrome mouse model and patients, the endothelial barrier is disrupted and involved in hyposecretion and lymphocytic infiltration. These findings enrich our understanding of the secretory mechanisms that link the importance of epithelial and endothelial TJ functions to salivation under both physiological and pathophysiological conditions.
Topics: Mice; Animals; Humans; Tight Junctions; Sjogren's Syndrome; Endothelial Cells; Salivary Glands; Saliva; Submandibular Gland; Sialorrhea
PubMed: 36825434
DOI: 10.1111/odi.14549 -
The Journal of Dermatology Jun 2022Psoriasis and atopic dermatitis are inflammatory skin diseases, and these patients have an increased risk of cardiovascular events and other medical complications. It...
Psoriasis and atopic dermatitis are inflammatory skin diseases, and these patients have an increased risk of cardiovascular events and other medical complications. It has been clarified that skin inflammation affects internal organs. Additionally, dental caries tends to occur more frequently in patients with psoriasis and atopic dermatitis. In this study, we aim to investigate the effects of dermatitis on the salivary glands using an inflammation model mouse. Salivary secretion stimulated with pilocarpine was reduced in dermatitis mice. Histologically, dermatitis mice showed amyloid deposition, glandular atrophy, and fibrosis in the salivary glands. Expression of inflammatory cytokines in the salivary glands was higher in dermatitis mice; however, secretion of cytokines in saliva was not significantly different. Dermatitis mice showed decreased salivary secretion and histological changes, which may cause periodontal disease. Therefore, appropriate control of skin inflammation is essential.
Topics: Animals; Atrophy; Cytokines; Dental Caries; Dermatitis, Atopic; Humans; Inflammation; Mice; Psoriasis; Salivary Glands
PubMed: 35257417
DOI: 10.1111/1346-8138.16334 -
Polish Journal of Pathology : Official... 2022Podoplanin (D2-40) is a lymphatic endothelial marker that is considered as a specific marker for lymphatic endothelial cells and lymphangiogenesis in salivary gland...
Podoplanin (D2-40) is a lymphatic endothelial marker that is considered as a specific marker for lymphatic endothelial cells and lymphangiogenesis in salivary gland carcinomas (SGCs). Aim: the present study aimed to investigate the immunohistochemical expression of podoplanin in SGCs and to correlate its expression with the clinicopathological parameters and patients' survival. Forty-nine SGC cases were electronically selected. Demographic, clinical, laboratory, and survival data were reviewed and tabulated. Immunohistochemistry was performed using antipodoplanin. Cases were divided into low and high expression based on a scoring system. A score of 0 and 1 was considered low expression, while > 1 was considered high expression. Podoplanin high expression was seen in 46.9% of cases, and 53.1% of cases showed low expression. Significant statistical associations were seen between podoplanin expression and tumour grade ( p ≤ 0.001), tumour-nodal- metastasis (TNM) stage (p ≤ 0.001), tumour size (p ≤ 0.001), nodal metastasis (p ≤ 0.001), tumour type (p = 0.03), prognosis (p ≤ 0.001), and mortality (p ≤ 0.001). The overall survival and progression-free survival differed significantly in cases with high and low expression (p ≤ 0.001). Podoplanin overexpression might be a significant prognostic indicator for patients with SGCs, implicating that it is a potential therapeutic target to improve survival in these cancer patients.
Topics: Humans; Clinical Relevance; Endothelial Cells; Lymphatic Metastasis; Prognosis; Salivary Gland Neoplasms; Carcinoma; Salivary Glands; Biomarkers, Tumor
PubMed: 36946268
DOI: 10.5114/pjp.2022.125820 -
Journal of Molecular Histology Oct 2021Salivary glands are considered the chief exocrine glands of the mouth and physiologically contribute to the maintenance of the homeostasis of the oral cavity. They... (Review)
Review
Salivary glands are considered the chief exocrine glands of the mouth and physiologically contribute to the maintenance of the homeostasis of the oral cavity. They consist of the parotid, submandibular and sublingual glands, which come in pairs and are collectively called the major glands, and the minor glands, which are much smaller and are dispersed throughout the buccal cavity. Salivary glands are distinguished by their size, amount of saliva secretion and their location in the oral cavity. Salivary glands pathophysiology has been a subject of interest in various worldwide metabolic disorders, including diabetes mellitus. Diabetes mellitus (DM), a global health concern, with a pathological imprint involved in vasculature, promotes microvascular and macrovascular complications among which periodontitis ranks sixth. Indeed, DM has also been directly associated with oral health lesions. Specifically, salivary glands in the context of diabetes have been a focal point of study and emphasis in the research field. There is evidence that relates salivary secretion content and diabetes progression. In this review, we present all the reported evidence of the deregulation of specific salivary proteins associated with the progression of diabetes in parallel with changes in salivary gland morphology, cellular architecture, and salivary secretion and composition more generally.
Topics: Animals; Diabetes Mellitus; Humans; Models, Biological; Oxidative Stress; Salivary Glands; Salivary Proteins and Peptides
PubMed: 34212290
DOI: 10.1007/s10735-021-09999-5 -
Head & Face Medicine Feb 2021Neurofibromin, a protein encoded by the NF1 gene, is mutated in neurofibromatosis 1, one of the most common genetic diseases. Oral manifestations are common and a high...
INTRODUCTION
Neurofibromin, a protein encoded by the NF1 gene, is mutated in neurofibromatosis 1, one of the most common genetic diseases. Oral manifestations are common and a high prevalence of hyposalivation was recently described in individuals with neurofibromatosis 1. Although neurofibromin is ubiquitously expressed, its expression levels vary depending on the tissue type and developmental stage of the organism. The role of neurofibromin in the development, morphology, and physiology of salivary glands is unknown and a detailed expression of neurofibromin in human normal salivary glands has never been investigated.
AIM
To investigate the expression levels and distribution of neurofibromin in acinar and ductal cells of major and minor salivary glands of adult individuals without NF1.
MATERIAL AND METHOD
Ten samples of morphologically normal major and minor salivary glands (three samples of each gland: parotid, submandibular and minor salivary; and one sample of sublingual gland) from individuals without neurofibromatosis 1 were selected to assess neurofibromin expression through immunohistochemistry. Immunoquantification was performed by a digital method.
RESULTS
Neurofibromin was expressed in the cytoplasm of both serous and mucous acinar cells, as well as in ducts from all the samples of salivary glands. Staining intensity varied from mild to strong depending on the type of salivary gland and region (acini or ducts). Ducts had higher neurofibromin expression than acinar cells (p = 0.003). There was no statistical association between the expression of neurofibromin and the type of the salivary gland, considering acini (p = 0.09) or ducts (p = 0.50) of the four salivary glands (parotid, submandibular, minor salivary, and sublingual gland). Similar results were obtained comparing the acini (p = 0.35) and ducts (p = 0.50) of minor and major salivary glands. Besides, there was no correlation between the expression of neurofibromin and age (p = 0.08), and sex (p = 0.79) of the individuals, considering simultaneously the neurofibromin levels of acini and duct (n = 34).
CONCLUSION
Neurofibromin is expressed in the cytoplasm of serous and mucous acinar cells, and ductal cells of salivary glands, suggesting that this protein is important for salivary gland function.
Topics: Adult; Genes, Neurofibromatosis 1; Humans; Neurofibromin 1; Parotid Gland; Salivary Glands; Sublingual Gland; Submandibular Gland
PubMed: 33602260
DOI: 10.1186/s13005-021-00256-4