- Low miR200b-5p levels in minor salivary glands: a novel molecular marker predicting lymphoma development in patients with Sjögren's syndrome. [Journal Article]
- ARAnn Rheum Dis 2018 May 19
- CONCLUSIONS: These findings support that miR200b-5p levels in MSGs represent a novel predictive and possibly pathogenetic mechanism-related factor for the development of SS-associated NHL, since its expression is impaired years before lymphoma clinical onset.
- Salivary gland-protective regulatory T cell dysfunction underlies female-specific sialadenitis in the nonobese diabetic mouse model of Sjögren syndrome. [Journal Article]
- IImmunology 2018 May 11
- Immune cell-mediated destruction of salivary glands is a hallmark feature of Sjögren syndrome. Similar to the female predominance in humans, female nonobese diabetic (NOD) mice develop spontaneous sa...
Immune cell-mediated destruction of salivary glands is a hallmark feature of Sjögren syndrome. Similar to the female predominance in humans, female nonobese diabetic (NOD) mice develop spontaneous salivary gland autoimmunity. However, in both humans and mice it is unclear what factors contribute to the initial immune infiltration of the salivary glands. Here, we used an adoptive transfer model of Sjögren syndrome to determine if female mice harbor a sex-specific defect in salivary gland-protective regulatory T (Treg) cells. Transfer of cervical lymph node (LN) cells from female NOD mice into sex-matched NOD-SCID recipients resulted in sialadenitis, regardless of the presence or absence of Treg cells. In contrast, transfer of cervical LN cells from male NOD mice into sex-matched NOD-SCID recipients only resulted in sialadenitis when Treg cells were depleted prior to transfer, suggesting male NOD mice have functional salivary-gland protective Treg cells. Notably, the host environment affected the ability of Treg cells to prevent sialadenitis with testosterone promoting salivary gland protection. Male Treg cells did not protect against sialadenitis in female recipients. Testosterone treatment of female recipients of bulk cervical LN cells decreased sialadenitis, and female Treg cells were capable of protecting against development of sialadenitis in male recipients. Thus, our data demonstrate that female NOD mice develop sialadenitis due to a defect in salivary gland-protective Treg cells that can be reversed in the presence of testosterone. This article is protected by copyright. All rights reserved.
- Inhibitory Effects of iPSC-MSCs and Their Extracellular Vesicles on the Onset of Sialadenitis in a Mouse Model of Sjögren's Syndrome. [Journal Article]
- SCStem Cells Int 2018; 2018:2092315
- No effective treatment for Sjögren's syndrome (SS), a chronic autoimmune disease affecting mainly salivary and lacrimal glands, is available now. Systemic infusion of allogeneic mesenchymal stem cell...
No effective treatment for Sjögren's syndrome (SS), a chronic autoimmune disease affecting mainly salivary and lacrimal glands, is available now. Systemic infusion of allogeneic mesenchymal stem cells (MSCs) isolated from tissues such as bone marrow (BM) alleviated SS in mouse models and a small clinical trial, but further research and application of this MSC therapy were hindered by limited expandability, significant donor variations, and safety concerns of tissue-derived MSCs. To circumvent these issues, we derived MSCs from human iPSCs using an optimized protocol that can be easily scaled up to produce a huge amount of standardized MSCs. Our iPSC-MSCs inhibited the onset of lymphocyte infiltration into salivary glands in the NOD mouse model of SS in the same way as BM-MSCs. Extracellular vesicles (EVs) carry bioactive molecules in the same way as their originating cells and are more stable and considered much safer than cells for therapies. We found that EVs derived from BM-MSCs and iPSC-MSCs suppressed activation of immune cells and expression of proinflammation factors essential for SS progression in vitro and that infusion of iPSC-MSC EVs at the predisease stage decreased the lymphocyte infiltration in salivary glands and serum autoantibody levels in the same way as infusion of BM-MSCs and iPSC-MSCs. These data suggested that iPSC-MSC EVs have the potential to prevent the progression of SS before the onset of sialadenitis.
- The association with xerostomia from sialadenitis and the jaw osteonecrosis in head and neck cancer population: a nationwide cohort study. [Journal Article]
- COClin Oral Investig 2018 May 03
- CONCLUSIONS: There was a close association between sialadenitis and ONJ in the HNC population. The severity of sialadenitis was positive correlated to ONJ risk. Radiotherapy combined with sialadenitis significantly raised ORN incidence in HNC patients except for NPC patients.HNC patients complained that xerostomia from sialadenitis might increase the risk to develop ONJ, especially among those who received radiotherapy.
- Hepatitis C Infection and Periodontal Disease: Is there a Common Immunological Link? [Review]
- JIJ Immunol Res 2018; 2018:8720101
- Hepatitis C virus (HCV) infections could have an important impact on the oral health status of patients, favoring conditions such as periodontal disease and oral cancer. The review of the existing sc...
Hepatitis C virus (HCV) infections could have an important impact on the oral health status of patients, favoring conditions such as periodontal disease and oral cancer. The review of the existing scientific literature written in English was performed, searching for oral and periodontal manifestations of HCV infection and its impact on the oral fluids. HCV infection can determine direct extrahepatic manifestations at the oral and periodontal level including oral lichen planus, Sjögren-like sialadenitis, and oral cancer. The changes caused by the infection in the subjects' immune system, diet, and lifestyle can facilitate the development of oral conditions such as periodontal disease. Important changes also occur in the composition of the infected patients' saliva and gingival fluid. HCV-infected patients need to be carefully monitored in terms of oral health since the infection with the virus can result in oral complications. The cellular and molecular particularities of the gingival fluid of HCV-infected patients can answer some questions regarding its impact upon periodontium impairment and whether this refers to a possible bidirectional relationship, with hepatic biomarker adjustments being induced by the periodontal patients' inflammatory status.
- Impact on Clinical Follow-up of the Milan System for Salivary Gland Cytology: A Comparison with a Traditional Diagnostic Classification. [Journal Article]
- CCytopathology 2018 May 03
- CONCLUSIONS: MSRSGC was comparable with the original reported diagnoses in the majority of cases. Both systems had high accuracy for distinguishing benign from malignant lesions and both were associated with appropriate follow-up in most cases. This article is protected by copyright. All rights reserved.
- Lack of evidence that nephrolithiasis increases the risk of sialolithiasis: A longitudinal follow-up study using a national sample cohort. [Journal Article]
- PlosPLoS One 2018; 13(4):e0196659
- CONCLUSIONS: There is no evidence of an increased risk of sialolithiasis associated with nephrolithiasis. We suggest that routine evaluation for sialolithiasis in all patients with nephrolithiasis is not necessary.
- Nivolumab-induced sialadenitis. [Journal Article]
- RCRespirol Case Rep 2018; 6(5):e00322
- Nivolumab has been increasingly used for a range of malignancies, and a variety of immune-related adverse events (irAEs) have been reported with its use. Nivolumab-induced sialadenitis (inflammation ...
Nivolumab has been increasingly used for a range of malignancies, and a variety of immune-related adverse events (irAEs) have been reported with its use. Nivolumab-induced sialadenitis (inflammation of salivary glands) and xerostomia (dry mouth) have been reported to occur in 0.03% and 0.05% respectively, but there have been no case reports published about these side effects. Sialadenitis is not a life-threatening irAEs, but xerostomia can become irreversible if not recognized and treated as it can otherwise lower quality of life and result in susceptibility to infection. Therefore, healthcare providers need to know about sialadenitis as one of the irAEs of Nivolumab. Thus, we present the first case of nivolumab-induced sialadenitis. A 70-year old man with pulmonary adenocarcinoma developed sialadenitis 4 months after initiating nivolumab. His serum amylase levels were elevated to 1373 IU/L, and a biopsy of his labial minor salivary glands showed severe lymphocytic inflammation with damage to the glands. His sialadenitis was improved by taking corticosteroids and by ceasing nivolumab.
- Anti-IL-7 receptor-α treatment ameliorates newly established Sjögren's-like exocrinopathy in non-obese diabetic mice. [Journal Article]
- BBBiochim Biophys Acta 2018; 1864(7):2438-2447
- The levels of interleukin (IL)-7 and its receptor are elevated in the salivary glands of patients with Sjögren's syndrome (SS). Our previous study indicates that IL-7 plays a critical pathogenic role...
The levels of interleukin (IL)-7 and its receptor are elevated in the salivary glands of patients with Sjögren's syndrome (SS). Our previous study indicates that IL-7 plays a critical pathogenic role in the development and onset of SS in a mouse model of this disease. The present study aims at determining whether IL-7 also plays a role in sustaining SS pathologies after the disease onset, by using the non-obese diabetic (NOD) model. Intraperitoneal administration of a blocking antibody against the IL-7 receptor α chain (IL-7Rα) to female NOD mice aged 10 weeks, which exhibited newly onset clinical SS, for the duration of 3 weeks significantly ameliorated characteristic SS pathologies including hyposalivation and leukocyte infiltration of the submandibular glands (SMGs). These changes were accompanied by a decrease in IFN-γ-producing CD4 T- and CD8 T cells, B cells, and lymphocyte chemoattractants CXCL9, -10, -11 and -13 in the SMGs. Anti-IL-7Rα treatment markedly diminished the amount of TNF-α in the SMGs and increased the level of claudin-1 and aquaporin 5, two molecules critical for normal salivary secretion. Furthermore, neutralization of IFN-γ and TNF-α, individually or in combination, considerably improved salivary secretion, reduced leukocyte infiltration and down-regulated CXCL9 and -13 expression in the SMGs. Collectively, the results indicate that endogenous IL-7R signals promote Th1 and Tc1 responses and IFN-γ- and TNF-α production to sustain the persistence of SS-like sialadenitis in NOD mice. These findings suggest that IL-7 and Th1 cytokines could serve as promising therapeutic targets for this prevalent autoimmune disease.
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- Ultrasound elastography in diagnosis and follow-up for patients with sialolithiasis. [Journal Article]
- DRDentomaxillofac Radiol 2018 May 03; :20170424
- CONCLUSIONS: ARFI provides an easy, quick and reliable diagnostic tool for the objective assessment of disease severity and progression in patients with sialolithiasis that can simply be implemented in pre-existing ultrasound protocols.