Infiltration Of Salivary Glands Research Articles

Autoantigen-specific B cells and plasma cells are prominent in areas of fatty infiltration in salivary glands of patients with primary Sjögren’s syndrome

Salivary and lacrimal gland involvement is a characteristic feature of primary Sjögren’s syndrome (pSS), where tissue destruction is mediated by mononuclear cell infiltration, resulting in lacrimal and salivary gland impairment. We have previously shown distinct prevalence of adipose tissue replacement in the minor salivary gland tissue from pSS patients. The salivary gland microenvironment was further examined through microarray analysis, identifying signalling pathways that promoted adipose tissue development, inflammation, and lymphoma. As B cells may also contribute to disease progression, we now aimed to study the B cell pattern with regard to adipocyte development in pSS. Double immunohistochemical staining of paraffin-embedded salivary gland tissue from 22 pSS patients and 11 non-SS tissue controls was employed, using the characteristic pSS autoantigens Ro52 or Ro60, alongside CD27. Additional CD138/CD20 double staining was also performed to identify the plasma- and general B- cell pattern. Our results demonstrated CD27-positive Ro52 and Ro60 specific cells observed within and in close proximity to the adipose tissue. CD138-positive plasma cells were also seen in areas of adipose tissue replacement, while the CD20+ cells were located within focal infiltrates, forming distinct B cell zones. The quantification of CD138+ and CD20+ cells revealed elevated numbers of CD138+ cells in areas of fatty infiltration, and also interstitially, in the salivary glands of pSS patients when compared to non-SS controls. A significant increase (p < .01) in CD138+ cells close to areas of fatty infiltration, and interstitially, with increasing fatty infiltration and focus score was further observed in pSS patients. A correlation between the number of CD20+ B cell zones/mm2 of salivary gland tissue and focus score values was also witnessed in the patients (r2 = 0.6047, p < .001). In conclusion, autoantigen-specific B cells and plasma cells appear prominent in areas of fatty infiltration in salivary glands of pSS patients, where an increase in CD138+ plasma cells and CD20+ B cells, in relation to both fatty and focal infiltration, suggests their active involvement in promoting inflammation. Further studies are needed to assess whether these adipocytes are also a result of tissue repair.

Helicobacter Pylori Infection in Sjögren's Syndrome: Co-incidence or Causality?

Lymphoid cell infiltration and destruction of exocrine glands, specifically lacrimal and salivary glands are characteristics of Sjogren's syndrome (SS). An etiological role has been proposed for Helicobacter pylori (H. pylori), interacting in the clinical course and complications of SS (including gastric cancer and lymphoma). The aim of this study was to identify the probable correlation between H. pylori infection and Sjogren's syndrome (SS). In this case-control study, ELISA method was used to determine serum level of IgA and IgM anti H. pylori antibody in 43 subjects with SS according to the international criteria and 95 healthy subjects as control. SPSS-17 was used to analyze data with t-test. P value <0.05 were considered significant. Serum level of IgM (34.9% vs. 10.5%, p-value= 0.001) and IgA (67.4% vs. 46.3% p value= 0.021) anti H. pylori antibody were significantly higher in SS patients compared to the control group. There was a positive correlation between age and H. pylori infection (r=0.2, Pvalue= 0.05). Patients with SS had a higher prevalence of H. pylori infection compared to the normal population. Eradication of H. pylori is recommended particularly in older patients with SS.

Blockade of CD40–CD154 pathway interactions suppresses ectopic lymphoid structures and inhibits pathology in the NOD/ShiLtJ mouse model of Sjögren’s syndrome

ObjectiveTo examine the role of CD40–CD154 costimulation and effects of therapeutic pathway blockade in the non-obese diabetic (NOD/ShiLtJ) model of Sjögren’s syndrome (SS).MethodsWe assessed leucocyte infiltration in salivary glands (SGs)...

PB1685 RELAPSE OF ACUTE LYMPHOBLASTIC LEUKEMIA MIMICKING MIKULICZ SYNDROME DURING BLINATUMUMAB TREATMENT: A CASE REPORT

Background:Mikulicz syndrome is a rare immune mediated condition characterized by tumor‐like swelling, lymphoplasmacytic infiltrate and fibrosis of salivary and lacrimal glands of poorly understood etiology. Its clinical presentation in the course of treating acute leukemia can be hard to differentiate from progression of the disease. We present a challenging diagnostic case of extramedullary acute lymphoblastic leukemia (ALL) relapse in the course of blinatumumab.Aims:Case report that aims to remember that AAL relapse can mimic any clinical picture.Methods:A 42‐year‐old woman was diagnosed in May 2017 with acute pro‐B lymphoblastic leukemia Ph negative, EGIL B‐II. Treatment with intensive multiagent chemotherapy according to PETHEMA high risk group was started. After induction, patient achieved complete response (CR) with negative minimal residual disease (MRD). Four additional courses of chemotherapy were completed following the PETHEMA high risk schedule. First relapse occurred and salvage therapy with Fludarabine, Ara‐C and Idarubicin was started achieving 2nd CR. Unfortunately, the patient relapsed three months later in the bone marrow and blinatumumab was decided. Two cycles were administered without neurological toxicities achieving CR with MRD of 0.31% and 0.11% after 1st and 2nd cycles, respectively. On 26th day of the 3rd cycle, acute swelling of both submandibular glands, swelling of right parotid gland and right monocular diplopia were observed. Cervical and cranial magnetic resonance was performed (Image 1) showing significant enlargement of the right lacrimal gland and bilateral submandibular glands. Bone marrow aspiration (BMA) showed CR with improved MRD of 0.02%. Cytological and cytometric cerebrospinal fluid analysis did not find ALL infiltration. With no evidence of disease progression and given the characteristics of the clinical and radiological picture, Mikulicz Syndrome was raised as a probable diagnostic possibility. However, a submandibular glandular tru‐cut biopsy showed glandular infiltration by ALL cells. One week later, a body PET/CT found significant metabolic uptake activity in the glands, regional lymph nodes and extensive bone involvement. Then, a new BMA (performed 10 days after de previous one) demonstrated ALL massive medullar relapse.Results:Relapsed/refractory (R/R) ALL is a bad condition with poor survival. Isolated extramedullary ALL relapse occurs in up to 6% of ALL according to literature and is often hard to demonstrate. In our case, the picture started as neck and head glandular swelling and diplopia. In the absence of medullar disease, Mikulicz Syndrome was suspected. Mikulicz Syndrome is a rare immune chronic benign condition characterized of swelling of neck and head glands where diplopia is often the first clinical sign. It has been related with several diseases including sarcoidosis, lymphoma and acute lymphoblastic leukemia. In this scenario, a biopsy of the involved glands is strongly recommended to rule out leukemia progression. In our case, tru‐cut biopsy of one of the involved glands demonstrated AAL extramedullary relapse despite absence of medullar involvement. Unfortunately, massive medullar relapse was confirmed a week later.Summary/Conclusion:Mikulicz syndrome is a diagnostic challenge for clinicians. In the setting of patients with ALL under blinatumumab treatment, clinicians should rule out ALL relapse before confirming this rare condition.image

Ly9 (CD229) Antibody Targeting Depletes Marginal Zone and Germinal Center B Cells in Lymphoid Tissues and Reduces Salivary Gland Inflammation in a Mouse Model of Sjögren's Syndrome.

Sjögren's Syndrome (SjS) is a common chronic autoimmune disease characterized by the B cell hyperactivation, lymphocyte infiltration, and tissue damage of exocrine glands. It can also present life-threatening extraglandular manifestations, such as pulmonary and hepatic involvement, renal inflammation and marginal zone (MZ) B cell lymphoma. Several biologic agents have been tested in SjS but none has shown significant efficacy. Here, we report the effects of Ly9 (CD229) antibody targeting, a cell surface molecule that belongs to the SLAM family of immunomodulatory receptors, using NOD.H-2h4 mice as a model of SjS-like disease. Female mice were treated with anti-Ly9 antibody or isotype control at week 24, when all mice present SjS related autoantibodies, salivary gland infiltrates, and marginal zone (MZ) B cell pool enlargement. Antibody injection depleted key lymphocyte subsets involved in SjS pathology such as MZ, B1, and germinal center B cells in spleen and draining lymph nodes without inducing a general immunosuppression. Importantly, mice receiving anti-Ly9 mAb showed a reduced lymphocyte infiltrate within salivary glands. This reduction may be, in part, explained by the down-regulation of L-selectin and alfa4/beta7 integrin induced by the anti-Ly9 antibody. Furthermore, levels of anti-nuclear autoantibodies were reduced after anti-Ly9 treatment. These data indicate that Ly9 is a potential therapeutic target for the treatment of SjS.

Mesenchymal stem cell transplantation ameliorates Sj\xf6gren\u2019s syndrome via suppressing IL-12 production by dendritic cells

BackgroundMesenchymal stem cells (MSCs) have been demonstrated to be effective in treating autoimmune diseases including Sjögren’s syndrome (SS). We aim to compare the effects of MSC transplantation (MSCT) and the role of serum interleukin-12 (IL-12) in SS.MethodsIL-12 levels were measured by ELISA. IL-12 mRNA transcripts in dendritic cells (DCs) were determined by RT-PCR. After co-culturing with MSCs, IL-12 mRNA transcripts in mouse and human DCs were detected. Non-obese diabetic (NOD) mice received MSCT, recombinant IL-12, or anti-IL-12 mAb treatment, respectively. Then, salivary flow rates, histopathology of salivary glands, and splenic lymphocyte subsets were examined in these mice.ResultsIL-12 levels in the serum were significantly increased in SS patients and positively correlated with the EULAR 2010 Sjögren’s syndrome disease activity index. DCs from SS patients produced more IL-12 than those from the control. Likewise, IL-12 treatment in NOD mice significantly decreased salivary flow rates and promoted lymphocyte infiltration in salivary glands. IL-12 antibodies downregulated Th1, Th17, and Tfh cell. MSCT enhanced salivary flow rates and decreased lymphocyte infiltrations in salivary glands of NOD mice. MSCT downregulated Th17 and Tfh cells but upregulated regulatory T cells. MSCT reduced IL-12 productions in both SS patients and mice.ConclusionOur results indicate that MSCs ameliorate SS possibly via suppressing IL-12 production in DCs and that IL-12 could be a potential therapeutic target of SS.Trial registrationNTC00953485. Registered June 2009.

Involvement of Aquaporins in the Pathogenesis, Diagnosis and Treatment of Sjögren's Syndrome.

Sjögren’s syndrome (SS) is a chronic autoimmune disease characterized by lymphocytic infiltration of salivary and lacrimal glands resulting in diminished production of saliva and tears. The pathophysiology of SS has not yet been fully deciphered. Classically it has been postulated that sicca symptoms in SS patients are a double step process whereby lymphocytic infiltration of lacrimal and salivary glands (SG) is followed by epithelial cell destruction resulting in keratoconjunctivitis sicca and xerostomia. Recent advances in the field of the pathophysiology of SS have brought in new players, such as aquaporins (AQPs) and anti AQPs autoantibodies that could explain underlying mechanistic processes and unveil new pathophysiological pathways offering a deeper understanding of the disease. In this review, we delineate the link between the AQP and SS, focusing on salivary glands, and discuss the role of AQPs in the treatment of SS-induced xerostomia.

Clinical and immunological parameters of Sjögren's syndrome.

Sjögren's syndrome (SS) is a chronic autoimmune disease that primarily affects the exocrine glands, resulting in their functional impairment. In SS, lymphocytic infiltration of salivary and lacrimal glands, and deposition of several types of autoantibodies, mainly anti-SS-A (anti-Ro) and anti-SS-B (anti-La), lead to chronic inflammation, with xerostomia and keratoconjunctivitis sicca. In its primary form (pSS), SS does not involve additional connective tissue diseases, whereas in its secondary and more common form (sSS), SS presents in association with other rheumatic autoimmune diseases, mainly rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). As in most autoimmune diseases, environmental, hormonal and genetic factors are implicated in SS pathogenesis. In SS T cells predominate in mild lesions, whereas B cells predominate in advanced lesions. Th1, Th2, Th17, follicular helper T (Tfh) cells and regulatory cells (Tregs/Bregs), with their characteristic cytokine profiles, have been implicated in the pathogenesis of SS. It has been suggested that Th1 and Th17 cells initiate SS and, as the disease progresses, Th2 and Tfh cells predominate. It is assumed that, as in all autoimmune and inflammatory conditions, tolerance defects contribute to SS pathogenesis. It is intriguing that in SS it remains unclear which types of regulatory cells are functional and whether they ameliorate or worsen the disease. In this review we present a comprehensive update on SS with emphasis on immune system involvement, and suggest new insights into SS immunopathogenesis.

Disruption of endothelial barrier function is linked with hyposecretion and lymphocytic infiltration in salivary glands of Sjögren's syndrome

Sjögren's syndrome (SS) is an inflammatory autoimmune disease that causes hyposecretion in salivary glands. Endothelial tight junctions (TJs) play crucial roles in salivation and barrier function of blood vessels. However, whether the alteration of endothelial TJs were involved in pathogenesis of SS was still unknown. Here, the ultrastructure and function of endothelial TJs in submandibular glands (SMGs) were detected by transmission electron microscopy and in vivo paracellular permeability assay in different aged NOD mouse model for SS. CFSE-labeled lymphocytes were injected into tail vein to trace the infiltration, while claudin-5 expression and distribution were detected by immunofluorescence, qRT-PCR, and western blot. Results showed that the stimulated salivary flow rate was gradually decreased and lymphocytic infiltration was found as age increased in 12- and 21-week-old NOD mice, but not 7-week-old NOD mice. Blood vessels were dilated, while endothelial TJ width and paracellular tracer transport were increased in 12-week-old NOD mice. Moreover, the injected CFSE-labeled lymphocytes were observed in SMGs of 12-week-old NOD mice. Claudin-5 level was increased and relocalized from the apical portion of neighboring endothelial cells to lateral membranes and cytoplasm in 12-week-old NOD mice. Additionally, the alteration of claudin-5 expression and distribution was further confirmed in labial salivary glands and bilateral parotid glands from SS patients. In cultured human microvessel endothelial cell line (HMEC-1), IFN-γ stimulation significantly increased claudin-5 expression. Taken together, we identified that the endothelial TJ barrier was disrupted and contributed to the development of salivary hyposecretion and lymphocytic infiltration in SS.

Aire is not essential for regulating neuroinflammatory disease in mice transgenic for human autoimmune-diseases associated MHC class II genes HLA-DR2b and HLA-DR4

The human autoimmune disease-associated HLA alleles HLA-DR2b (DRB1*1501) and HLA-DR4 (DRB1*0401) are strongly linked to increased susceptibility for multiple sclerosis (MS) and rheumatoid arthritis (RA), respectively. The underlying mechanisms are not fully understood, but these MHC alleles may shape the repertoire of pathogenic T cells via central tolerance. The transcription factor autoimmune regulator (AIRE) promotes central T cell tolerance via ectopic expression of tissue-specific antigens (TSAs). Aire deficiency in humans causes autoimmune polyendocrinopathy syndrome type 1 (APS1), and Aire knockout mice (Aire−/−) develop spontaneous autoimmune pathology characterized by multi-organ lymphocytic infiltrates.Here, we asked whether impaired TSAs gene expression in the absence of Aire promoted spontaneous MS- or RA-like autoimmune pathology in the context of human HLA alleles in HLA-DR2b or HLA-DR4 transgenic (tg) mice.The results show that reduced TSAs gene expression in the thymus of Aire-deficient HLA-DR2b or HLA-DR4 tg mice corresponded to mild spontaneous inflammatory infiltrates in salivary glands, liver, and pancreas. Moreover, Aire-deficiency modestly enhanced experimental autoimmune encephalomyelitis (EAE) in HLA-DR tg mice, but the animals did not show signs of spontaneous neuroinflammation or arthritis. No significant changes were observed in CD4+ T cell numbers, T cell receptor (TCR) distribution, regulatory T cells (Treg), or antigen-induced cytokine production. Abrogating Treg function by treatment with anti-CTLA-4 or anti-CD25 mAb in Aire-deficient HLA-DR tg mice did not trigger EAE or other autoimmune pathology. Our results suggest a redundant role for Aire in maintaining immune tolerance in the context of autoimmune disease-associated human HLA alleles.

Cytokine markers of B lymphocytes in minor salivary gland infiltrates in Sjögren's syndrome.

Sjögren's syndrome (SS) is a chronic autoimmune disorder characterised by the clinical presence of sicca syndrome. SS compromises the dysfunction of exocrine glands due to the presence of focal, mononuclear cell infiltrates that surround the ducts and replace the secretory units. Abnormal expression of different cytokines and chemokines such as B-cell activating factor, CXC Motif Chemokine Ligand 13, interleukin 6 (IL-6), IL-22, and FMS-like tyrosine kinase 3 ligand as well as that of their corresponding receptors has been implicated in the inflammatory process. The severity of glandular infiltration has been suggested to be associated with the presence of extra-glandular systemic manifestations, contributing to a clinical spectrum of the most severe disease. This review describes several cytokines and chemokines associated with B lymphocytes expressed in the minor salivary gland, their chemical structures, and their roles in SS as possible early predictors of lymphoma development and disease progression.

Clinical features and risk factors of neurological involvement in Sj\xf6gren\u2019s syndrome

BackgroundTo investigated distinct manifestations of Sjögren’s syndrome (SS) patients with neurological complications and the potential risk factors associated with neurological complications in SS, and to produce a disease evaluation and neurological involvement prediction for SS.Methods566 patients who fulfilled the 2002 classification criteria for SS from the Rheumatology Department of the First Affiliated Hospital of Wenzhou Medical University were included in the cross-sectional study. Clinical, immunological and histological characteristics were surveyed, and potential risk factors for neurological complications were examined by multivariate analysis.ResultsAmong 566 SS patients, 184 (32.5%) patients had neurological involvement, with more than 10% got limbs pain, limbs numbness and cerebral infarction, respectively. Of these 184 SS patients with neurological complications, secondary SS (sSS) patients had a higher prevalence of peripheral nervous system (PNS) involvement than primary SS (pSS) patients (31.1 vs. 19%). And sSS patients showed higher total ESSPRI score and higher prevalence of xerostomia and low C3, C4 levels with more liver, articular involvement and saliva gland atrophy, and more severe lymphocyte infiltration in salivary glands than pSS patients. As for the specific factors associated with neurological involvement, low C3 level were found to be significant in pSS or sSS patients who were younger 50 year old, and ANA positivity, cardiac involvement, saliva gland atrophy were demonstrated to be associated in elder pSS patients. And xerophthalmia was found to be associated in sSS patients.ConclusionLow complement (C3) levels, xerophthalmia, ANA positive, cardiac involvement and labial salivary gland histological result were good ways to predict neurological complications in different subgroups of SS, which might provide insight into better clinical decision-making, especially at early stages of the disease.

Inhibitory Effects of iPSC-MSCs and Their Extracellular Vesicles on the Onset of Sialadenitis in a Mouse Model of Sjögren's Syndrome.

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.

Fatty infiltration of the minor salivary glands is a selective feature of aging but not Sjögren’s syndrome

Objective: Determine the presence and assess the extent of fatty infiltration of the minor salivary glands (SG) of primary SS patients (pSS) as compared to those with non-SS sicca (nSS).Methods: Minor SG biopsy samples from 134 subjects with pSS (n = 72) or nSS (n = 62) were imaged. Total area and fatty replacement area for each glandular cross-section (n = 4–6 cross-sections per subject) were measured using Image J (National Institutes of Health, Bethesda, MD). The observer was blinded to subject classification status. The average area of fatty infiltration calculated per subject was evaluated by logistic regression and general linearized models (GLM) to assess relationships between fatty infiltration and clinical exam results, extent of fibrosis and age.Results: The average area of fatty infiltration for subjects with pSS (median% (range) 4.97 (0.05–30.2)) was not significantly different from that of those with nSS (3.75 (0.087–41.9). Infiltration severity varied widely, and subjects with fatty replacement greater than 6% were equivalently distributed between pSS and nSS participants (χ2 p = .50). Age accounted for all apparent relationships between fatty infiltration and fibrosis or reduced saliva flow. The all-inclusive GLM for prediction of pSS versus non-SS classification including fibrosis, age, fatty replacement, and focus score was not significantly different from any desaturated model. In no iteration of the model did fatty replacement exert a significant effect on the capacity to predict pSS classification.Conclusions: Fatty infiltration is an age-associated phenomenon and not a selective feature of Sjögren’s syndrome. Sicca patients who do not fulfil pSS criteria have similar rates of fatty infiltration of the minor SG.

89Zr-labeled nivolumab for imaging of T-cell infiltration in a humanized murine model of lung cancer.

Nivolumab is a human monoclonal antibody specific for programmed cell death-1 (PD-1), a negative regulator of T-cell activation and response. Acting as an immune checkpoint inhibitor, nivolumab binds to PD-1 expressed on the surface of many immune cells and prevents ligation by its natural ligands. Nivolumab is only effective in a subset of patients, and there is limited evidence supporting its use for diagnostic, monitoring, or stratification purposes. 89Zr-Df-nivolumab was synthesized to map the biodistribution of PD-1-expressing tumor infiltrating T-cells in vivo using a humanized murine model of lung cancer. The tracer was developed by radiolabeling the antibody with the positron emitter zirconium-89 (89Zr). Imaging results were validated by ex vivo biodistribution studies, and PD-1 expression was validated by immunohistochemistry. Data obtained from PET imaging were used to determine human dosimetry estimations. The tracer showed elevated binding to stimulated PD-1 expressing T-cells in vitro and in vivo. PET imaging of 89Zr-Df-nivolumab allowed for clear delineation of subcutaneous tumors through targeting of localized activated T-cells expressing PD-1 in the tumors and salivary glands of humanized A549 tumor-bearing mice. In addition to tumor uptake, salivary and lacrimal gland infiltration of T-cells was noticeably visible and confirmed via histological analysis. These data support our claim that PD-1-targeted agents allow for tumor imaging in vivo, which may assist in the design and development of new immunotherapies. In the future, noninvasive imaging of immunotherapy biomarkers may assist in disease diagnostics, disease monitoring, and patient stratification.

Proteasome inhibition ameliorates experimental Sjögren’s syndrome by suppressing Th17 and B cell responses

Abstract Primary Sjögren’s syndrome (SS) is a chronic autoimmune disease that mainly affects salivary and lacrimal glands. Currently, there is a lack of effective therapies for SS patients. Increasing evidence indicates that Bortezomib (BTZ), the first proteasome inhibitor approved for treating multiple myeloma, shows beneficial effects in treating lupus. Although clinical findings have revealed increased expression of proteasome in SS patients, it remains unclear whether proteasome inhibition is an effective approach for treating SS. In this study, we evaluated the therapeutic effects of BTZ on experimental SS (ESS) mouse model. Mice were immunized with proteins extracted from salivary glands (SG) to induce ESS and received either vehicle or BTZ treatment. Compared with vehicle-treated counterparts, BTZ-treated mice displayed markedly higher saliva flow rates and ameliorated tissue destructions accompanied with less lymphocytes infiltration in SG. Notably, mice with BTZ treatment showed significantly decreased Th17 but not Th1 responses, and reduced germinal center B cells and plasma cells in peripheral lymphoid organs. In culture, BTZ treatment significantly suppressed Th17 cells differentiation and proliferation. Moreover, adoptively transferred naïve CD4 T cells differentiated into Th17 cells and induced salivary dysfunction in immunized Il17a−/− mice. However, the BTZ-treated recipient mice exhibited suppressed Th17 responses with ameliorated reduction in salivary secretion. Taken together, our findings have shown that BTZ treatment can suppress Th17 and B cell responses and effectively ameliorate ESS development in mice, which may contribute to the validation of BTZ as a promising candidate for treating SS.

Adipose tissue infiltration in minor salivary glands of patients with Sjögren’s syndrome: Lack of significant correlation with the disease. An image analysis of 174 cases

Fatty infiltration in minor salivary gland biopsies and its correlation to systemic autoimmune diseases are controversial in the literature. Presence and extent of fatty infiltration in minor salivary glands of 107 Sjögren’s syndrome patients and 67 age-matched sicca controls were compared with statistical analyses. No significant difference was found regarding the presence or the extent of fatty infiltration between the two groups. Fatty infiltration seems to be unrelated to Sjögren’s syndrome thus its examination in salivary gland biopsy samples cannot improve the diagnostic accuracy of the disease.

Effect of Excess Iodide Intake on Salivary Glands in a Swiss Albino Mice Model.

Iodine is an important micronutrient required for nutrition. Excess iodine has adverse effects on thyroid, but there is not enough information regarding its effect on salivary glands. In addition to food and iodized salt, skin disinfectants and maternal nutritional supplements contain iodide, so its intake could be excessive during pregnancy, lactation, and infancy. The aim of this work was to evaluate the effect of excess iodide ingestion on salivary glands during mating, gestation, lactation, and postweaning period in mouse. During assay, mice were allocated into groups: control and treatment groups (received distilled water with NaI 1 mg/mL). Water intake, glandular weight, and histology were analyzed. Treatment groups showed an increase in glandular weight and a significantly (p < 0.05) higher water intake than control groups. Lymphocyte infiltration was observed in animals of treatment groups, while there was no infiltration in glandular sections of control groups. Results demonstrated that a negative relationship could exist between iodide excess and salivary glands. This work is novel evidence that high levels of iodide intake could induce mononuclear infiltration in salivary glands. These results should be considered, especially in pregnant/lactating women, to whom a higher iodine intake is usually recommended.

Characteristics of primary Sjögren's syndrome patients with IgG4 positive plasma cells infiltration in the labial salivary glands.

The purpose of this study was to investigate the characteristics of primary Sjögren's syndrome (pSS) patients with IgG4 positive (IgG4+) plasma cell infiltration in labial salivary glands (LSGs). Paraffin sections of LSGs from 336 pSS patients were stained with IgG4 and IgG monoclonal antibodies. According to the infiltration of IgG4+ plasma cells, patients were divided and clinical and serological characteristics were analyzed and compared. Based on the infiltration of IgG4+ plasma cells in the LSGs, patients were divided into three subgroups, low IgG4, moderate IgG4, and high IgG4 groups. A negative association between the number of infiltrated IgG4+ plasma cells and the disease characteristics was observed. We found that the higher the IgG4+ expression in plasma cells, the lower the positive rates of serum anti-SSA antibodies, anti-SSB antibodies, antinuclear antibodies (ANA), and rheumatoid factor (RF). Besides, patients from the high IgG4 group had the highest frequency of interstitial lung disease (ILD, 30.6%) and tubulointerstitial nephritis (TIN, 13.9%), but the lowest frequency of leucopenia (13.9%), thrombocytopenia (11.1%), and abnormal thyroidal function (0%). PSS patients with different IgG4+ plasma cells infiltration in the LSGs had distinctive clinical and laboratory characteristics. It may help us to further understand the role of IgG4+ plasma cells in pSS.

BOTOX-A injection of salivary glands for drooling

Background and purposeDrooling is a challenging entity to manage. Botulinum toxin A (BOTOX-A) infiltration of salivary glands is a promising alternative to surgical treatment. This study aims to assess the outcome of BOTOX-A salivary glands infiltration in children with drooling. MethodsPatients treated between January 2012 and March 2015 were enrolled. BOTOX-A was injected in the parotid and submandibular glands under ultrasound control and general inhalational anesthesia. The outcome was evaluated through the DSFS: Drooling Severity (1-best to 5-worst) and Frequency (1 to 4) Scale, that was applied before treatment, and 1-, 3-, and 6-month after injection. The inclusion criteria were a DSS ≥4 and/or DFS ≥3. Statistical significance was set at 5%. ResultsThere were 17 patients aged 12.1±5.1 [4–19]years, all of them with neurologic impairment. After the first injection, 13 (76.5%) patients had reduction of the severity (S) and 12 (70.6%) of the frequency (F) scale; in 6 (35.5%) patients drooling resolved completely. Pre-treatment S+F score was 8.59±0.71 [7–9]; it decreased significantly to 4.65±2.32 (p=0.001) at 1-month post-injection evaluation. At 3-month and 6-month the scores were also significantly lower than the pre-treatment one (4.00±1.96, p=0.002; 5.36±2.20, p=0.005; respectively), but there was a significant increase between the 3-month and 6-month evaluations (p=0.01). With a follow-up of 20.1±9.2 [4–38] months, 4 out of the 13 successful injections needed a second one after 7.5±3.1 [3–10] months. The patient with the longest time not requiring re-injection had 28months of follow-up.One (6%) patient presented mild dysphagia that regressed spontaneously. All but two (88%) parents/caregivers would repeat the treatment. ConclusionsBOTOX-A seems to be an effective minimal invasive treatment for drooling with few complications. After 6months the need for re-injection becomes substantial but it may not be necessary for several months. Further studies are needed to establish the most effective dosage and frequency of injections. Level of evidenceIV