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1.
Clin Immunol ; 264: 110258, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38762063

ABSTRACT

Lymphocytes such as CD4+ T cells and B cells mainly infiltrate the salivary glands; however, the precise roles and targets of autoreactive T cells and autoantibodies in the pathogenesis of Sjögren's Syndrome (SS) remain unclear. This study was designed to clarify the role of autoreactive T cells and autoantibodies at the single-cell level involved in the development of sialadenitis. Infiltrated CD4+ T and B cells in the salivary glands of a mouse model resembling SS were single-cell-sorted, and their T cell receptor (TCR) and B cell receptor (BCR) sequences were analyzed. The predominant TCR and BCR clonotypes were reconstituted in vitro, and their pathogenicity was evaluated by transferring reconstituted TCR-expressing CD4+ T cells into Rag2-/- mice and administering recombinant IgG in vivo. The reconstitution of Th17 cells expressing TCR (#G) in Rag2-/- mice resulted in the infiltration of T cells into the salivary glands and development of sialadenitis, while an autoantibody (IgGr22) was observed to promote the proliferation of pathogenic T cells. IgGr22 specifically recognizes double-stranded RNA (dsRNA) and induces the activation of dendritic cells, thereby enhancing the expression of IFN signature and inflammatory genes. TCR#G recognizes antigens related to the gut microbiota. Antibiotic treatment severely reduces the activation of TCR#G-expressing Th17 cells and suppresses sialadenitis development. These data suggest that the anti-dsRNA antibodies and, TCR recognizing the gut microbiota involved in the development of sialadenitis like SS. Thus, our model provides a novel strategy for defining the roles of autoreactive TCR and autoantibodies in the development and pathogenesis of SS.


Subject(s)
Autoantibodies , Receptors, Antigen, T-Cell , Sialadenitis , Sjogren's Syndrome , Animals , Sjogren's Syndrome/immunology , Sialadenitis/immunology , Autoantibodies/immunology , Mice , Receptors, Antigen, T-Cell/immunology , Receptors, Antigen, T-Cell/genetics , Mice, Knockout , Salivary Glands/immunology , Mice, Inbred C57BL , CD4-Positive T-Lymphocytes/immunology , Disease Models, Animal , B-Lymphocytes/immunology , Th17 Cells/immunology , Female , Receptors, Antigen, B-Cell/immunology , DNA-Binding Proteins/immunology , DNA-Binding Proteins/genetics
2.
J Cutan Pathol ; 51(1): 53-57, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37669870

ABSTRACT

Ointment pseudo-cheilitis is a recently recognized distinctive type of self-induced cheilitis. Lesions consist of a variable amount of crusts adhered to the vermilion. These crusts consist of dried saliva and dead cells mixed with applied medications attached to the lip surface. Patients are typically severely anxious or depressed; the condition impacts quality of life. Ointment pseudo-cheilitis is frequently misdiagnosed as exfoliative cheilitis or cheilitis glandularis. Biopsy reports are often non-revealing because there are no established histopathological criteria for this disease, and clinicians usually do not formulate the correct diagnostic hypothesis. Here, we present the histopathological findings of four cases of ointment pseudo-cheilitis. The most consistent finding was the presence of laminated parakeratotic material detached from the epithelium in biopsies that are devoid of other significant diagnostic changes. This material at the lip surface possibly represents physiologic labial desquamation mixed with dried saliva and applied medication. With this report, we intend to alert dermatopathologists to the diagnosis of ointment pseudo-cheilitis if they receive biopsies from patients who present clinically exuberant labial lesions that show only minimal histopathological changes.


Subject(s)
Cheilitis , Sialadenitis , Female , Humans , Cheilitis/diagnosis , Cheilitis/pathology , Ointments , Quality of Life , Sialadenitis/pathology , Biopsy , Lip/pathology
3.
Int J Med Sci ; 21(3): 492-495, 2024.
Article in English | MEDLINE | ID: mdl-38250604

ABSTRACT

Purpose: Our aim was to evaluate the effect of prophylactic pilocarpine on acute salivary symptoms after radioactive iodine (RAI) therapy in patients with differentiated thyroid cancer. Methods: We enrolled 88 patients (76 women and 12 men; mean age: 47 years; range: 20-74 years) with differentiated thyroid cancer who received RAI. Patients were divided into pilocarpine (51 patients) and control (37 patients) groups. Pilocarpine was given orally, at a dose of 5 mg three times a day, from 2 days before and 12 days after RAI therapy. Symptoms and signs of acute sialadenitis within 3 months of RAI therapy were recorded. Results: During the 3 months after RAI therapy, 13 of the 88 patients (14.7%) developed acute symptomatic sialadenitis (swelling or pain of salivary glands). Acute salivary symptoms were reported by 4 (7.8%) and 9 (24.3%) patients in the pilocarpine and control groups, respectively. Acute salivary symptoms were less frequent in the pilocarpine than control group (p = 0.04), but did not differ by age, sex, or RAI dose (p = 0.3357, p = 0.428, and p = 0.2792). Conclusions: Pilocarpine reduced the likelihood of acute sialadenitis after RAI therapy in patients with differentiated thyroid cancer.


Subject(s)
Adenocarcinoma , Sialadenitis , Thyroid Neoplasms , Male , Humans , Female , Middle Aged , Thyroid Neoplasms/drug therapy , Thyroid Neoplasms/radiotherapy , Iodine Radioisotopes/adverse effects , Pilocarpine/adverse effects , Sialadenitis/etiology , Sialadenitis/prevention & control , Acute Disease
4.
Am Fam Physician ; 109(6): 550-559, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38905553

ABSTRACT

The major salivary glands are the paired parotid, submandibular, and sublingual glands. Salivary gland disorders can affect the glandular tissue or its excretory system. The parotid glands are the largest and produce aqueous serous secretions that are less immunogenic. They are more susceptible to infections and neoplasms. The submandibular glands produce mucinous secretions that are high in calcium and phosphate salts through a long submandibular duct that flows against gravity. The submandibular glands are responsible for more than 80% of salivary stones. Sialadenitis can be acute or chronic and caused by bacterial, viral, and obstructive etiologies; the most common bacteria is Staphylococcus aureus. The most common viral etiologies in children are mumps (globally) and juvenile recurrent parotitis (in vaccinated populations). Sialadenosis is a chronic asymptomatic enlargement of the salivary glands due to systemic disease. Sialolithiasis causes up to 50% of salivary gland disorders. It is associated with salivary stasis and inflammation caused by dehydration, malnutrition, medications, or chronic illness. Obstruction is also caused by trauma, stenosis, and mucoceles. Neoplasms are rare and typically benign, but they warrant referral and imaging with ultrasonography, computed tomography, or magnetic resonance sialography. Most disorders are managed with conservative measures by treating the underlying etiology, optimizing predisposing factors, controlling pain, and increasing salivary flow with sialagogues, hydration, massage, warm compresses, oral hygiene, and medication adjustment. Sialendoscopy is a gland-sparing technique that can treat obstructive and nonobstructive disorders. (Am Fam Physician. 2024;109(6):550-559.


Subject(s)
Salivary Gland Diseases , Humans , Salivary Gland Diseases/diagnosis , Salivary Gland Diseases/therapy , Salivary Gland Diseases/etiology , Sialadenitis/diagnosis , Sialadenitis/therapy
5.
J Am Anim Hosp Assoc ; 60(2): 68-73, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38394695

ABSTRACT

A 3 yr old female spayed Labrador retriever was referred for the treatment of a chronic oropharyngeal stick injury. After computed tomography scan evaluation, the cervical area was explored surgically and a right-sided cervical abscess that contained a wooden stick was identified adjacent to the vagosympathetic trunk and carotid artery. The ipsilateral mandibular salivary gland was resected concurrently given its abnormal appearance, and histology confirmed inflammation and necrosis of the gland, which was suspected to be due to direct trauma from the foreign body. The clinical signs initially improved but then recurred, and a follow-up computed tomography scan was suggestive of sialadenosis or sialadenitis in the right parotid, zygomatic, and molar salivary glands. A presumptive diagnosis of sialadenosis was made and a course of phenobarbital was initiated. The clinical signs resolved completely within a few days, and there was no recurrence several months after termination of the phenobarbital treatment. This is the first case report of presumptive sialadenosis in a dog as a suspected complication of an oropharyngeal stick injury. Informed consent was obtained from the owner of the dog and the patient was managed according to contemporary standards of care.


Subject(s)
Dog Diseases , Sialadenitis , Dogs , Female , Animals , Dog Diseases/drug therapy , Sialadenitis/diagnosis , Sialadenitis/veterinary , Sialadenitis/pathology , Oropharynx/injuries , Oropharynx/pathology , Phenobarbital , Parotid Gland/pathology
6.
J Assoc Physicians India ; 72(8): 93-95, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39163078

ABSTRACT

Granulomatosis with polyangiitis (GPA) is a pauci-immune vasculitis typically involving upper and lower respiratory tract involvement and crescentic glomerulonephritis. Salivary gland involvement in GPA is rare. When it occurs in GPA, it is commonly seen with sinonasal and lung involvement and rarely with renal involvement. Easy accessibility of salivary glands allows early biopsy and timely treatment. In our case with GPA, salivary gland involvement was unresponsive to cyclophosphamide but remitted with rituximab.


Subject(s)
Granulomatosis with Polyangiitis , Rituximab , Sialadenitis , Humans , Sialadenitis/diagnosis , Granulomatosis with Polyangiitis/diagnosis , Granulomatosis with Polyangiitis/drug therapy , Granulomatosis with Polyangiitis/complications , Rituximab/therapeutic use , Cyclophosphamide/therapeutic use , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/diagnosis , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis/complications , Male , Antibodies, Antineutrophil Cytoplasmic/blood , Antibodies, Antineutrophil Cytoplasmic/immunology , Immunosuppressive Agents/therapeutic use , Middle Aged , Female
7.
Mod Rheumatol ; 34(3): 632-638, 2024 Mar 28.
Article in English | MEDLINE | ID: mdl-37747366

ABSTRACT

OBJECTIVES: To identify the specific microRNAs (miRNAs) in IgG4-related dacryoadenitis and sialadenitis (IgG4-DS) and predict the targeted genes. METHODS: miRNAs in the serum of nine patients with IgG4-DS, three patients with primary Sjögren's syndrome, and three healthy controls were analysed using the human miRNA chip, and miRNAs that exhibited significant fluctuation in expression in IgG4-DS patients were extracted. The respective target genes were predicted using an existing database, and expression of the target genes was evaluated in actual submandibular gland tissues affected by IgG4-DS. RESULTS: Serum miR-125a-3p and miR-125b-1-3p levels were elevated in IgG4-DS. Six candidate target genes (glypican 4, forkhead box C1, protein tyrosine phosphatase non-receptor type 3, hydroxycarboxylic acid receptor 1, major facilitator superfamily domain containing 11, and tumour-associated calcium signal transducer 2) were downregulated in the affected submandibular gland tissue. CONCLUSION: Overexpression of miR-125a-3p and miR-125b-1-3p is a hallmark of IgG4-DS. These miRNAs appear to be involved in the pathogenesis of IgG4-DS.


Subject(s)
Dacryocystitis , MicroRNAs , Sialadenitis , Sjogren's Syndrome , Humans , MicroRNAs/genetics , Sjogren's Syndrome/genetics , Immunoglobulin G , Sialadenitis/genetics , Dacryocystitis/genetics
8.
Int Immunol ; 34(12): 621-634, 2022 12 31.
Article in English | MEDLINE | ID: mdl-36044992

ABSTRACT

Autoimmune pancreatitis (AIP) and IgG4-related disease (IgG4-RD) are new disease entities characterized by enhanced IgG4 antibody responses and involvement of multiple organs, including the pancreas and salivary glands. Although the immunopathogenesis of AIP and IgG4-RD is poorly understood, we previously reported that intestinal dysbiosis mediates experimental AIP through the activation of IFN-α- and IL-33-producing plasmacytoid dendritic cells (pDCs). Because intestinal dysbiosis is linked to intestinal barrier dysfunction, we explored whether the latter affects the development of AIP and autoimmune sialadenitis in MRL/MpJ mice treated with repeated injections of polyinosinic-polycytidylic acid [poly (I:C)]. Epithelial barrier disruption was induced by the administration of dextran sodium sulfate (DSS) in the drinking water. Mice co-treated with poly (I:C) and DSS, but not those treated with either agent alone, developed severe AIP, but not autoimmune sialadenitis, which was accompanied by the increased accumulation of IFN-α- and IL-33-producing pDCs. Sequencing of 16S ribosomal RNA revealed that Staphylococcus sciuri translocation from the gut to the pancreas was preferentially observed in mice with severe AIP co-treated with DSS and poly (I:C). The degree of experimental AIP, but not of autoimmune sialadenitis, was greater in germ-free mice mono-colonized with S. sciuri and treated with poly (I:C) than in germ-free mice treated with poly (I:C) alone, which was accompanied by the increased accumulation of IFN-α- and IL-33-producing pDCs. Taken together, these data suggest that intestinal barrier dysfunction exacerbates AIP through the activation of pDCs and translocation of S. sciuri into the pancreas.


Subject(s)
Autoimmune Diseases , Autoimmune Pancreatitis , Immunoglobulin G4-Related Disease , Pancreatitis , Sialadenitis , Mice , Animals , Pancreatitis/chemically induced , Pancreatitis/pathology , Dysbiosis , Interleukin-33 , Pancreas/pathology , Mice, Inbred Strains , Poly I-C , Interferon-alpha , Sialadenitis/pathology
9.
Cell Mol Biol (Noisy-le-grand) ; 69(15): 217-222, 2023 Dec 31.
Article in English | MEDLINE | ID: mdl-38279438

ABSTRACT

IgG4-related sialadenitis is a systemic autoimmune disease that can lead to fibro-inflammatory conditions. This study aims to investigate the immune microenvironment and potential signaling pathways associated with IgG4-related sialadenitis. Datasets related to IgG4-related sialadenitis were retrieved from the GEO database. Immune cell infiltration analysis was conducted using the Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) method. Differentially immune-related expressed genes (DIEG) and immune-related functional enrichment were identified. Moreover, potential treatment targets for IgG4-related sialadenitis were predicted using The Connectivity Map. Only two datasets from GEO were included for further analysis. The CIBERSORT results indicated dominant immune cell populations in IgG4-related sialadenitis, including CD8+ T cells, resting NK cells, monocytes, and naïve B cells in peripheral blood mononuclear cells. Additionally, high abundance of plasma cells was observed in labial salivary gland tissues. Furthermore, a total of 42 DIEGs were identified, with tumor necrosis factor (TNF) signaling via the NF-Kappa B signaling pathway and the p53 signaling pathway being highly enriched. Autophagy inhibitors and DNA topoisomerase inhibitors were strongly associated with potential targets for the treatment of IgG4-related sialadenitis (P<0.05). This study reveals altered immune microenvironment in peripheral blood mononuclear cells and labial salivary gland tissues in IgG4-related sialadenitis. Autophagy inhibitors and DNA topoisomerase inhibitors show promise as potential targets for treating IgG4-related sialadenitis, providing a novel therapeutic strategy for this disease.


Subject(s)
Immunoglobulin G , Sialadenitis , Humans , Leukocytes, Mononuclear/pathology , Sialadenitis/drug therapy , Sialadenitis/pathology , Plasma Cells , Topoisomerase Inhibitors/therapeutic use
10.
Oral Dis ; 29(3): 1005-1016, 2023 Apr.
Article in English | MEDLINE | ID: mdl-34826194

ABSTRACT

OBJECTIVES: This study aimed to evaluate the level of oxidative stress (OS) in human and rat chronic sialadenitis (CS) of the submandibular gland (SMG). METHOD: We collected human SMG tissues and established a rat CS model using Wharton's duct partial ligation (PL). Morphological changes in the SMG were evaluated by HE, Sirius Red, AB/PAS, TUNEL and immunohistochemical (IHC) staining. Oxidative damage and antioxidant capacity were detected by ELISA, commercial assay kits and IHC staining to evaluate their expression levels and locations in the SMG. RESULTS: Histopathological damage were observed in the human and rat CS. In rat PL group, the oxidative damage products (8-OHdG, AOPP, 8-iso-PGF2α and H2 O2 ) were significantly increased. For antioxidants, the PL group had markedly decreased T-AOC and CAT activity, but markedly increased SOD activity. 3-NT, 4-HNE and MDA expression changed during the process of CS, and antioxidant enzymes (CAT, SOD1, SOD2, GPX1 and GPX4) were mainly expressed in ducts. CONCLUSIONS: The oxidative-antioxidant imbalance of CS in human and rats was revealed, the different expression of oxidative damage during the process of CS was detected, and the different antioxidant reaction in acinar and ductal cells was demonstrated.


Subject(s)
Sialadenitis , Submandibular Gland , Humans , Rats , Animals , Submandibular Gland/pathology , Antioxidants , Sialadenitis/pathology , Chronic Disease , Oxidative Stress
11.
Oral Dis ; 29(4): 1579-1587, 2023 May.
Article in English | MEDLINE | ID: mdl-35113467

ABSTRACT

OBJECTIVES: Cheilitis Glandularis (CG) is an uncommon entity of obscure etiology. A cases series is presented with emphasis on etiopathogenesis. MATERIALS AND METHODS: Fourteen CG cases were analyzed according to their demographic and clinicopathologic characteristics. RESULTS: The mean age of the patients with CG was 68.1 years, while a male-to-female ratio of 1.8:1 was observed. One or more potential causative factors were identified for each patient, including long-term smoking (9 cases), xerostomia (4 cases), cosmetic filler injections (2 cases), and actinic cheilitis (1 case). The lesions were located on the lips, buccal mucosa, or both in 7, 2, and 5 cases, respectively. Multiple submucosal nodules with dilated ductal orifices and mucous or purulent discharge were observed in all cases. Histopathologically, ductal ectasia with metaplasia, intraductal mucin, and chronic or mixed inflammation were noted, as well as pools of hyaluronic acid in 2 cases with a history of cosmetic filler injections. CONCLUSIONS: CG etiopathogenesis is probably multifactorial. Reduced salivary flow rate and increased viscosity of saliva, potentially caused by long-term smoking, diabetes mellitus, and drug-induced xerostomia, may participate in the initial pathogenesis, while local irritants, for example, poor oral hygiene and local trauma, may further contribute to the development and aggravation of the condition.


Subject(s)
Cheilitis , Sialadenitis , Xerostomia , Humans , Male , Female , Aged , Salivary Glands, Minor , Cheilitis/etiology , Cheilitis/pathology , Sialadenitis/pathology , Xerostomia/complications
12.
Oral Dis ; 29(3): 990-995, 2023 Apr.
Article in English | MEDLINE | ID: mdl-34773326

ABSTRACT

Radiation therapy is a critical strategy for the treatment of malignant tumors. X-ray external radiation has been successfully used to treat head and neck cancer. On the other hand, 131 I internal radiation has been effective in managing differentiated thyroid cancer. However, these therapies cause radiation damage to salivary glands. Radiation sialadenitis is the most common complication associated with radiotherapy applied to the head and neck and it severely affects patients' quality of life. Since DNA is the main intracellular target of radiation, and the integrity of the DNA structure is critical to genomic stability and the cellular survival of salivary glands, regulating radiation-induced DNA damage offers great promise in preventing and managing radiation sialadenitis. In this review, we summarize recent progress in DNA damage and repair in irradiated salivary glands.


Subject(s)
Sialadenitis , Thyroid Neoplasms , Humans , Quality of Life , Sialadenitis/genetics , Sialadenitis/radiotherapy , Salivary Glands/physiology , DNA Damage , Thyroid Neoplasms/genetics , Thyroid Neoplasms/radiotherapy , Thyroid Neoplasms/complications , Iodine Radioisotopes
13.
J Ultrasound Med ; 42(10): 2235-2246, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37162711

ABSTRACT

OBJECTIVE: To assess the value of high-frequency ultrasonography in the evaluation of immunoglobulin G4-related submandibular sialadenitis (IgG4-SS). METHODS: Thirty-four submandibular glands in 17 patients with IgG4-SS were retrospectively enrolled, as well as 34 submandibular glands in 17 healthy control subjects. Qualitative ultrasonic features including submandibular gland size, border, echogenicity, and vascularity were reviewed. Two different scoring systems (0-16 and 0-48, respectively) were used for semi-quantitative analysis of imaging features. Comparison of both qualitative and semi-quantitative ultrasonic analysis were made between patients with IgG4-SS and healthy controls. Spearman correlation was used to explore relationships between variables. RESULTS: The submandibular glands with IgG4-SS presented with enlarged size, rough border, increased vascularity, and abnormal echogenicity (All P < .05). The most common echogenicity pattern for IgG-SS was diffuse hypoechoic foci pattern (44.1%), followed by superficial hypoechoic pattern (20.6%), tumor-like pattern (14.7%), and diffuse hypoechogenicity pattern (11.8%). Most IgG4-SS glands presented linear hyperechogenicity in parenchyma (91.2%). Based on both scoring system, scores of IgG4-SS were significantly higher than those of the controls (All P < .05). Association analysis of both scoring systems showed positive correlation of scores with vascularity in the gland parenchyma (All P < .05). CONCLUSION: The ultrasonic features of IgG4-SS comprise enlarged gland, rough border, increased vascularity, and abnormal echogenicity, which correlate with its pathological characteristics. The most common echogenicity pattern for IgG4-SS was diffuse hypoechoic foci pattern. Semi-quantitative analysis systems could be useful in the assessment of IgG4-SS. Ultrasound is a potential, valuable, and non-invasive tool for the diagnosis and evaluation of IgG4-SS.


Subject(s)
Sialadenitis , Humans , Retrospective Studies , Sialadenitis/diagnostic imaging , Sialadenitis/pathology , Ultrasonography/methods , Submandibular Gland/diagnostic imaging , Immunoglobulin G
14.
J Oral Maxillofac Surg ; 81(3): 344-349, 2023 03.
Article in English | MEDLINE | ID: mdl-36502857

ABSTRACT

PURPOSE: Sialendoscopy is a minimally invasive procedure for the treatment of salivary gland diseases. The purpose of this study was to review a series of the patients undergoing sialendoscopy and to present our experience regarding the management and outcome of obstructive sialadenitis treated by this procedure. METHODS: This study was a case series. We collected data on patients who underwent sialendoscopy in our institute between January 2016 and July 2019. The data included patients' demographics, involved salivary glands, diagnostic investigation, types of anesthesia, endoscopic findings, materials used, complications, adjunctive treatment, duration of follow-up, and therapeutic outcome. Descriptive statistics were used to analyze the surgical findings and outcome. RESULTS: There were 61 patients involving 76 glands (48 submandibular and 29 parotid glands). There were 43 females and 18 males with the median age 45 years at the time of sialendoscopy. The median duration of follow-up was 6 months. The most dominant symptom was pain with swelling (59.20%). The 2 most common sialendoscopic findings were ductal stenosis and sialolithiasis. We observed a success rate in achieving a complete relief of 77.6% at the first procedure and 96.7% at the last follow-up. We did not have any cases with postoperative complication or recurrence. CONCLUSION: Our study supports sialendoscopy as a safe and successful procedure that plays a dual role in diagnostics and in relieving symptoms of patients with obstructive sialadenitis with or without sialolithiasis. It should be advised for patients with non-neoplastic salivary duct obstruction either for diagnosis or therapeutic intervention.


Subject(s)
Anesthesia, Dental , Salivary Gland Calculi , Sialadenitis , Male , Female , Humans , Middle Aged , Salivary Gland Calculi/surgery , Treatment Outcome , Endoscopy/methods , Hospitals , Retrospective Studies
15.
Proc Natl Acad Sci U S A ; 117(12): 6630-6639, 2020 03 24.
Article in English | MEDLINE | ID: mdl-32161138

ABSTRACT

Aging elicits quantitative and qualitative changes in different immune components, leading to disruption of tolerogenic circuits and development of autoimmune disorders. Galectin-1 (Gal1), an endogenous glycan-binding protein, has emerged as a regulator of immune cell homeostasis by shaping the fate of myeloid and lymphoid cells. Here, we demonstrate that aged Gal1-null mutant (Lgals1-/- ) mice develop a spontaneous inflammatory process in salivary glands that resembles Sjögren's syndrome. This spontaneous autoimmune phenotype was recapitulated in mice lacking ß1,6N-acetylglucosaminyltransferase V (Mgat5), an enzyme responsible for generating ß1,6-branched complex N-glycans, which serve as a major ligand for this lectin. Lack of Gal1 resulted in CD11c+ dendritic cells (DCs) with higher immunogenic potential, lower frequency of Foxp3+ regulatory T cells (Tregs), and increased number of CD8+ T cells with greater effector capacity. Supporting its tolerogenic activity, Gal1 expression decreased with age in autoimmunity-prone nonobese diabetic (NOD) mice. Treatment with recombinant Gal1 restored tolerogenic mechanisms and reduced salivary gland inflammation. Accordingly, labial biopsies from primary Sjögren's syndrome patients showed reduced Gal1 expression concomitant with higher number of infiltrating CD8+ T cells. Thus, endogenous Gal1 serves as a homeostatic rheostat that safeguards immune tolerance and prevents age-dependent development of spontaneous autoimmunity.


Subject(s)
Autoimmune Diseases/pathology , Galectin 1/physiology , Immune Tolerance/immunology , Salivary Glands/pathology , Sialadenitis/pathology , Sjogren's Syndrome/pathology , T-Lymphocytes, Regulatory/immunology , Adult , Age Factors , Animals , Autoimmune Diseases/immunology , Autoimmune Diseases/metabolism , Case-Control Studies , Dendritic Cells/immunology , Female , Glycosylation , Humans , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Inbred NOD , Mice, Knockout , Middle Aged , N-Acetylglucosaminyltransferases/physiology , Polysaccharides/metabolism , Salivary Glands/immunology , Salivary Glands/metabolism , Sialadenitis/immunology , Sialadenitis/metabolism , Sjogren's Syndrome/immunology , Sjogren's Syndrome/metabolism
16.
Article in English | MEDLINE | ID: mdl-35817018

ABSTRACT

INTRODUCTION: Sialendoscopy is a minimally invasive technique for the management of salivary gland disease. This work characterizes its utility for treating chronic sialadenitis due to Sjogren's syndrome and radioactive iodine (RAI) therapy. METHODS: A single-center, retrospective review of patients undergoing sialendoscopy between March 2013 and May 2019 for the treatment of chronic sialadenitis due to Sjogren's or prior RAI therapy was performed. RESULTS: Thirty-four patients with Sjogren's and 25 patients who received RAI were identified, undergoing a total of 86 procedures. Median age at presentation was 53 years with mean follow-up time of 14.3 months. Seventy-two procedures were performed on the parotid gland, four on the submandibular gland, and ten on both glands. Corticosteroid injection and duct dilation were performed most commonly. Sixteen patients required repeat procedure. All patients were symptomatically improved at follow-up visit. DISCUSSION/CONCLUSION: These results support the idea that sialendoscopy offers symptomatic benefit for patients with chronic sialadenitis due to Sjogren's or RAI.


Subject(s)
Sialadenitis , Sjogren's Syndrome , Thyroid Neoplasms , Humans , Middle Aged , Sjogren's Syndrome/complications , Sjogren's Syndrome/radiotherapy , Sjogren's Syndrome/chemically induced , Iodine Radioisotopes/therapeutic use , Endoscopy/methods , Thyroid Neoplasms/surgery , Sialadenitis/etiology , Sialadenitis/surgery , Chronic Disease
17.
Int J Mol Sci ; 24(15)2023 Jul 30.
Article in English | MEDLINE | ID: mdl-37569583

ABSTRACT

Although multiple mouse strains have been advanced as models for Sjögren's syndrome (SS), which is a human systemic autoimmune disease characterized primarily as the loss of lacrimal and salivary gland functions, the C57BL/6.NOD-Aec1Aec2 recombinant inbred (RI) mouse derived from the NOD/ShiLtJ line is considered one of the more appropriate models exhibiting virtually all the characteristics of the human disease. This mouse model, as well as other mouse models of SS, have shown that B lymphocytes are essential for the onset and development of observed clinical manifestations. Recently, studies carried out in the C57BL/6.IL14α transgenic mouse have provided clear evidence that the marginal zone B (MZB) cell population is directly involved in the early pathological events initiating the development of the clinical SS disease, as well as late-stage lymphomagenesis resulting in B-cell lymphomas. Since MZB cells are difficult to study in vivo and in vitro, we carried out a series of ex vivo investigations that utilize temporal global RNA transcriptomic analyses to profile differentially expressed genes exhibiting temporal upregulation during the initial onset and subsequent development of pathophysiological events within the lacrimal and salivary gland tissues per se or associated with the leukocyte cell migrations into these glands. The initial transcriptomic analyses revealed that while the upregulated gene expression profiles obtained from lacrimal and salivary glands overlap, multiple genetic differences exist between the defined activated pathways. In the current study, we present a concept suggesting that the initial pathological events differ between the two glands, yet the subsequent upregulated TLR4/TLR3 signal transduction pathway that activates the type-1 interferon signature appears to be identical in the two glands and indicates an autoimmune response against dsRNA, possibly a virus. Here, we attempt to put these findings into perspective and determine how they can impact the design of future therapeutic protocols.


Subject(s)
Dacryocystitis , Sialadenitis , Sjogren's Syndrome , Mice , Humans , Animals , Mice, Inbred C57BL , Mice, Inbred NOD , B-Lymphocytes , Sialadenitis/genetics , Sialadenitis/metabolism , Dacryocystitis/genetics , Dacryocystitis/metabolism , Disease Models, Animal
18.
Int J Mol Sci ; 24(6)2023 Mar 09.
Article in English | MEDLINE | ID: mdl-36982329

ABSTRACT

Extracellular vesicles (EVs) from allogeneic-tissue-derived mesenchymal stem cells (MSCs) are promising to improve Sjögren's syndrome (SS) treatment, but their application is hindered by high variations in and limited expandability of tissue MSCs. We derived standardized and scalable MSCs from iPS cells (iMSCs) and reported that EVs from young but not aging iMSCs (iEVs) inhibited sialadenitis onset in SS mouse models. Here, we aim to determine cellular mechanisms and optimization approaches of SS-inhibitory effects of iEVs. In NOD.B10.H2b mice at the pre-disease stage of SS, we examined the biodistribution and recipient cells of iEVs with imaging, flow cytometry, and qRT-PCR. Intravenously infused iEVs accumulated in the spleen but not salivary glands or cervical lymph nodes and were mainly taken up by macrophages. In the spleen, young but not aging iEVs increased M2 macrophages, decreased Th17 cells, and changed expression of related immunomodulatory molecules. Loading miR-125b inhibitors into aging iEVs significantly improved their effects on repressing sialadenitis onset and regulating immunomodulatory splenocytes. These data indicated that young but not aging iEVs suppress SS onset by regulating immunomodulatory splenocytes, and inhibiting miR-125b in aging iEVs restores such effects, which is promising to maximize production of effective iEVs from highly expanded iMSCs for future clinical application.


Subject(s)
Extracellular Vesicles , Induced Pluripotent Stem Cells , Mesenchymal Stem Cells , MicroRNAs , Sialadenitis , Sjogren's Syndrome , Mice , Animals , Sjogren's Syndrome/therapy , Sjogren's Syndrome/drug therapy , Spleen/metabolism , Induced Pluripotent Stem Cells/metabolism , Tissue Distribution , Mice, Inbred NOD , Sialadenitis/therapy , Sialadenitis/metabolism , Extracellular Vesicles/metabolism , Mesenchymal Stem Cells/metabolism , MicroRNAs/metabolism , Disease Models, Animal
19.
Can Fam Physician ; 69(8): 531-536, 2023 08.
Article in English | MEDLINE | ID: mdl-37582587

ABSTRACT

OBJECTIVE: To provide family physicians with a practical evidence-based approach to the management of patients with sialadenitis. SOURCES OF INFORMATION: MEDLINE and PubMed databases were searched for English-language research on sialadenitis and other salivary gland disorders, as well as for relevant review articles and guidelines published between 1981 and 2021. MAIN MESSAGE: Sialadenitis refers to inflammation or infection of the salivary glands and is a condition that can be caused by a broad range of processes including infectious, obstructive, and autoimmune. History and physical examination play important roles in directing management, while imaging is often useful to establish a diagnosis. Red flags such as suspected abscess formation, signs of respiratory obstruction, facial paresis, and fixation of a mass to underlying tissue should prompt urgent referral to head and neck surgery or a visit to the emergency department. CONCLUSION: Family physicians can play an important role in the diagnosis and management of sialadenitis. Prompt recognition and treatment of the condition can prevent the development of complications.


Subject(s)
Sialadenitis , Humans , Sialadenitis/diagnosis , Sialadenitis/therapy , Sialadenitis/etiology , Diagnostic Imaging/adverse effects , Physical Examination
20.
BMC Oral Health ; 23(1): 347, 2023 06 01.
Article in English | MEDLINE | ID: mdl-37264360

ABSTRACT

BACKGROUND: The diagnosis of sialadenitis, the most frequent disease of the salivary glands, is challenging when the symptoms are mild. In such cases, biomarkers can be used as definitive diagnostic indicators. Recently, biomarkers have been developed by extracting and analyzing pathological and morphological features from medical imaging. This study aimed to establish a diagnostic reference for sialadenitis based on the quantitative magnetic resonance imaging (MRI) biomarker IDEAL-IQ and assess its accuracy. METHODS: Patients with sialadenitis (n = 46) and control subjects (n = 90) that underwent MRI were selected. Considering that the IDEAL-IQ value is a sensitive fat fractional marker to the body mass index (BMI), all subjects were also categorized as under-, normal-, and overweight. The fat fraction of parotid gland in the control and sialadenitis groups were obtained using IDEAL-IQ map. The values from the subjects in the control and sialadenitis groups were compared in each BMI category. For comparison, t-tests and receiver operating characteristic (ROC) curve analyses were performed. RESULTS: The IDEAL-IQ fat faction of the control and sialadenitis glands were 38.57% and 23.69%, respectively, and the differences were significant. The values were significantly lower in the sialadenitis group (P), regardless of the BMI types. The area under the ROC curve (AUC) was 0.83 (cut-off value: 28.72) in patients with sialadenitis. The AUC for under-, normal-, and overweight individuals were 0.78, 0.81, and 0.92, respectively. CONCLUSIONS: The fat fraction marker based on the IDEAL-IQ method was useful as an objective indicator for diagnosing sialadenitis. This marker would aid less-experienced clinicians in diagnosing sialadenitis.


Subject(s)
Parotid Gland , Sialadenitis , Humans , Parotid Gland/diagnostic imaging , Parotid Gland/pathology , Overweight , Sialadenitis/diagnostic imaging , Salivary Glands , Magnetic Resonance Imaging/methods
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