Labial Salivary Glands Of Patients Research Articles

Mitochondria-related genes and metabolic profiles of innate and adaptive immune cells in primary Sjögren's syndrome.

Primary Sjogren's syndrome (pSS) is a prototypical systemic autoimmune disease characterised by lymphocyte infiltration and immune-complex deposition in multiple organs. The specific distribution of immune cell populations and their relationship with mitochondria remain unknown. Histological analysis was performed to assess the specific distribution of innate and adaptive immune cell populations in labial salivary gland (LSG) samples from 30 patients with pSS and 13 patients with non-pSS. The ultrastructural morphometric features of mitochondria within immune cells were observed under the transmission electron microscope (TEM). RNA sequencing was performed on LSG samples from 40 patients with pSS and 7 non-pSS patients. The Single-sample Gene Set Enrichment Analysis (ssGSEA), ESTIMATE, and CIBERSORT algorithms and Pearson correlation coefficients were used to examine the relationship between mitochondria-related genes and immune infiltration. Weighted Gene Co-expression Network Analysis (WGCNA) was used to identify the mitochondria-specific genes and the related pathways based on the immune cell types. HE staining revealed a massive infiltration of plasma cells with abundant immunoglobulin protein distributed around phenotypically normal-appearing acinar and ductal tissues of patients with pSS. Immunohistochemical analyses revealed that innate immune cells (macrophages, eosinophils and NK cells) were distributed throughout the glandular tissue. Dominant adaptive immune cell infiltration composed of B cells, CD4+T cells and CD8+ T cells or ectopic lymphoid follicle-like structures were observed in the LSGs of patients with pSS. TEM validated the swelling of mitochondria with disorganised cristae in some lymphocytes that had invaded the glandular tissue. Subsequently, bioinformatic analysis revealed that innate and adaptive immune cells were associated with different mitochondrial metabolism pathways. Mitochondrial electron transport and respiratory chain complexes in the glandular microenvironment were positively correlated with innate immune cells, whereas amino acid and nucleic acid metabolism were negatively correlated with adaptive immune cells. In addition, mitochondrial biogenesis and mitochondrial apoptosis in the glandular microenvironment were closely associated with adaptive immune cells. Innate and adaptive immune cells have distinct distribution profiles in the salivary gland tissues of patients with pSS and are associated with different mitochondrial metabolic pathways, which may contribute to disease progression.

Are salivary flow rates associated with histopathologic aspects in patients with rheumatoid arthritis?

The aim of this retrospective cross-sectional study was to verify the association between salivary flow rates (SFR) and the histopathologic aspects of labial salivary glands (LSG) in patients with rheumatoid arthritis (RA). Patients presenting rheumatologic diseases referred for oral evaluation were included in the study if they had RA and had SFR measured and LSG biopsy performed. Patients were excluded if they had systemic conditions that affect SFR or if they were being treated for hyposalivation. Cases without enough material for histopathologic analysis were also excluded. Data were collected through questionnaires, oral examination, resting and stimulated SFR, and LSG biopsies. A histopathologic reevaluation was carried out in order to seek for additional histopathologic aspects. Fifty-one patients met the inclusion criteria. The mean age was 53.5 years (25-77), and 94.1% were women. The median resting and stimulated SFRs were 0.24 mL/min and 1.02 mL/min, respectively. The presence of lymphocytic focus and fibrosis were significantly associated with stimulated SFR, but not with resting SFR. The odds ratio of patients who had hyposalivation for presenting a positive lymphocytic focus was 7.33 (confidence interval CI: 1.53-35.23) by the stimulated technique, and 2.56 (CI: 0.57-11.40) in resting SFR. In the medical records, 14 (31.80%) patients had been diagnosed with secondary Sjögren's syndrome. In conclusion, stimulated SFR represent a good screening test to predict lymphocytic focus in LSG in patients with RA, which represents the most specific test to diagnose Sjögren's syndrome.

CMTM6: increased circulating level and up-regulated expression in labial salivary glands in patients with primary Sjogren's syndrome.

Chemokine-like factor (CKLF)-like MARVEL transmembrane domain containing family member 6 (CMTM6), which is a key regulator of programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) signaling in patients with primary Sjögren’s syndrome (pSS). In this study, we analyzed the serum levels of CMTM6, PD-1, and PD-L1 in 50 patients with pSS, 42 patients with non-pSS (simply dry mouth and/or eyes symptoms) and 50 healthy controls (HC). The expression of CMTM6, PD-1, and PD-L1 in labial glands of the same 50 pSS patients and 42 non-pSS patients were assessed by immunohistochemistry (IHC). The clinical significance of CMTM6, PD-1, and PD-L1 were analyzed. We found that levels of CMTM6, PD-L1 as well as PD-1 in sera were all increased significantly in patients with pSS compared with non-pSS controls and HC. Serum CMTM6 level showed significantly correlation with PD-L1, PD-1, as well as clinical laboratory indicators and disease activity of pSS patients. CMTM6, PD-1, and PD-L1 expression in labial glands was also higher significantly in pSS patients than non-pSS controls. pSS patients with higher CM grade or ESSDAI score have higher CMTM6, PD-L1, and PD-1 expression in labial glands. These results suggest that CMTM6 may affect peripheral tolerance and lymphocytes activation by PD-1/PD-L1 pathway in sera and target tissue in pSS.

Molecular Mechanism of Sphingosine-1-Phosphate Receptor 1 Regulating CD4+ Tissue Memory in situ T Cells in Primary Sjogren's Syndrome.

ObjectiveAlthough extensive research has been carried out on CD4+T cells infiltrating the labial glands in patients with primary Sjögren’s Syndrome (pSS), it is still unclear how CD4+T cells remain in the labial gland tissue and develop into tissue resident cells. The aim of this study was to investigate the molecular mechanism by which CD4+T reside in labial glandular tissue of pSS patients.MethodsLymphocyte infiltration in labial salivary glands (LSG) of pSS patients was detected by H&E staining. Expression of sphingosine-1-phosphate receptor 1 (S1PR1) in LSG was examined by Immunohistochemistry. Immunofluorescence analyses were utilized to detect the co-expression of CD4, CD69 and S1PR1 in T cells of LSG of pSS patients. Expression of gene S1pr1 in peripheral blood CD4+T cells of healthy controls and pSS patients was detected by quantitative real-time PCR (QPCR). QPCR was used to examine the expression of gene S1pr1, Klf2, and Cd69 in the CD4+T cells that were co-cultured in vitro with cytokines TNF-α, TGF-β, and IL-33.ResultsS1PR1 was expressed in the infiltrating monocytes in LSG of pSS patients, and S1PR1 was weakly or even not expressed in cytoplasm of CD4+CD69+TRM cells of LSG in patients with pSS. Expression of gene S1pr1 in peripheral blood CD4+T cells of pSS patients was about three-fifths of that of healthy controls (P < 0.05). Expression of genes S1pr1 (P < 0.001) and Klf-2 (P < 0.001) was significantly decreased, and the expression of gene Cd69 (P < 0.05) was significantly increased in peripheral blood CD4+T cells of pSS patients co-cultured in vitro with cytokines TNF-α, TGF-β, and IL-33.ConclusionOur study suggests that the decrease of S1pr1 gene expression may provide a molecular basis for promoting the tissue retention and development of CD4+CD69+TRM cells.

Inhibitory effect of HTLV-1 infection on the production of B-cell activating factors in established follicular dendritic cell-like cells.

IntroductionThe low frequency of ectopic germinal center in labial salivary glands of patients with human T‐cell leukemia virus type 1 (HTLV‐1) antibody‐positive Sjögren's syndrome (SS) suggests that HTLV‐1 has some effects on follicular dendritic cells (FDCs).MethodsWe used flow cytometry, immunofluorescence, and enzyme‐linked immunosorbent assays (ELISAs) to investigate the direct effect of HTLV‐1 on B‐cell activating factors produced by established FDC like cells obtained from excised human tonsils. We then measured the serum B‐cell activating factor (BAFF) and C‐X‐C motif ligand (CXCL) 13 concentrations of the HTLV‐1‐seropositive SS patients and the HTLV‐1‐seronegative SS patients by ELISA.ResultsAmong the 31 isolated specimens, 22 showed morphological characteristics of FDCs. Day 2‐cultured specimens showed expressions of CD14, CD23, CD40, intracellular adhesion molecule‐1 (ICAM‐1), and vascular cell adhesion molecule‐1. After 2 weeks, 12 of these specimens expressed ICAM‐1, FDC, and fibroblast cell marker. Intracellular BAFF and CXCL13 were constitutively expressed regardless of stimulation. After direct coculture with the HTLV‐1‐infected T‐cell line HCT‐5 or MT‐2, the BAFF and CXCL13 expressions on the FDC‐like cells were decreased in accord with the increased number of HCT‐5 and MT‐2 cells with styliform change and without HTLV‐1 Gag protein expression. Interferons upregulated the concentration of BAFF (but not CXCL13) in the culture supernatant, which showed a declining trend under the presence of HCT‐5 or MT‐2. The serum concentrations of BAFF and CXCL13 in the HTLV‐1‐seropositive SS patients were lower than those of the HTLV‐1 seronegative SS patients.ConclusionsHTLV‐1 partially inhibited the BAFF and CXCL13 expressions of established FDC‐like cells.

Upregulation and pathogenic roles of CCL18-CCR8 axis in IgG4-related disease

Objectives: To determine the protein expression level, expressing cell types, and pathogenic roles of chemokine (C-C motif) ligand 18 (CCL18) and its receptor chemokine (C-C motif) receptor 8 (CCR8) in affected tissues of patients with IgG4-related disease (IgG4-RD).Methods: The protein expression levels of CCL18 in labial salivary glands (LSGs) assessed by immunofluorescence (IF) staining were compared among patients with IgG4-RD (n = 3), primary Sjögren’s syndrome (pSS; n = 4), and control subjects (n = 5). CCL18 expression levels in macrophages, CD11c+ cells, B cells, and plasmacytes in LSGs were examined by double IF staining. The protein expression levels of CCR8 and expressing cells (T, B cells, and plasmacytes) in LSGs were also compared among patients with IgG4-RD, pSS, and control subjects by double IF staining. The effects of the CCL18-CCR8 axis on total IgG, IgG2, and IgG4 production by peripheral blood mononuclear cells (PBMCs) stimulated with CD40L, IL-4, IL-10, and IL-21 were examined by in vitro assays.Results: CCL18 was specifically upregulated in LSGs of patients with IgG4-RD, compared with only a few cells in pSS patients and none of the controls. The numbers of CCL18-producing macrophages, CD11c+ cells, and plasmacytes in LSGs were significantly higher in IgG4-RD patients than in pSS patients and control (p < .05, each). Many T and B cells and some plasmacytes expressed CCR8 in LSGs of IgG4-RD and pSS patients. CCL18 specifically enhanced IgG4 production by stimulated PBMCs.Conclusion: CCL18-CCR8 axis was upregulated in LSGs of patients with IgG4-RD, suggesting possible roles of this axis in the pathogenesis of IgG4-RD.Key messagesThe CCL18-CCR8 axis in labial salivary glands (LSGs) and lacrimal glands of IgG4-RD patients was specifically upregulated compared with primary Sjögren’s syndrome and control subjects.This axis might be a potentially novel therapeutic target in IgG4-RD, based on its important etiopathogenic roles, such as chemotaxis of various cells, induction of fibrosis, and enhancement of IgG4 production.

Tissue-Resident Memory CD8+ T Cells Acting as Mediatorsof Salivary Gland Damage in a Murine Model of Sjögren's Syndrome.

Although a role for CD4+ T cells in the pathogenesis of Sjögren's syndrome (SS) has been documented, the pathogenic significance of CD8+ T cells is unclear. The aim of this study was to investigate the role of CD8+ T cells in the development of SS. Flow cytometry and immunofluorescence analyses were utilized to detect T cell infiltration within the labial salivary glands of patients with primary SS. In parallel, p40-/- CD25-/- mice were used as a murine model of SS. In addition, mice with genetic knockout of CD4, CD8a, or interferon-γ (IFNγ) were crossed with p40-/- CD25-/- mice to study the pathogenic significance of specific lineage subpopulations, including functional salivary gland tests as well as histopathologic and serologic data. A CD8+ T cell-specific depletion antibody was used in this murine SS model to evaluate its potential as a therapeutic strategy. CD8+ T cells with a tissue-resident memory phenotype outnumbered CD4+ T cells in the labial salivary glands of patients with SS, and were primarily colocalized with salivary duct epithelial cells and acinar cells. Furthermore, infiltrating CD8+ T cells with a CD69+CD103+/- tissue-resident phenotype and with a significant elevation of IFNγ production were dominant in the submandibular glands of mice in this murine SS model. CD8a knockout abrogated the development of SS in these mice. Knockout of IFNγ decreased CD8+ T cell infiltration and gland destruction. More importantly, depletion of CD8+ T cells fully protected mice against the pathologic manifestations of SS, even after the onset of disease. These data reveal the pathogenic significance of CD8+ T cells in the development and progression of SS in the salivary glands. Treatment directed against CD8+ T cells may be a rational therapy for the management of SS in human subjects.

The role of ROR\u03b1 in salivary gland lesions in patients with primary Sj\xf6gren\u2019s syndrome

BackgroundThe orphan nuclear receptors retinoic acid-related receptor α and γt (RORα and RORγt) are critical in the development of T helper 17 (Th17) cells, and ROR-specific synthetic ligands have proven efficacy in several mouse models of autoimmunity. However, the pathological significance of RORα in primary Sjögren’s syndrome (pSS) remains to be elucidated. The present study was designed to clarify the significance of RORα in the pathogenesis of pSS.MethodsRORα expression in the labial salivary gland (LSG) was determined by immunohistochemical analysis using a quantitative scoring system in 34 patients with pSS. The correlation between RORα expression in LSGs and the focus score (FS) was determined, and Th17 and IL-17 receptor A (1L-17RA) levels in LSGs were determined. To investigate the effect of RORs and the therapeutic potential of targeting RORs in pSS, we administered SR1001, a selective RORα/γt inverse agonist, to non-obese diabetic (NOD) mice.ResultsThe expression of RORα was significantly increased in LSGs of patients with pSS and intensified with disease stage/FS, showing a similar increasing trend with IL-17A and IL-17RA. SR1001 significantly improved salivary gland secretory function and relieved sialadenitis in treated mice.ConclusionOur data reveal the importance of RORα in controlling pathologic lymphocytic infiltration of the salivary glands and suggest that RORα may be a druggable target in treating pSS.

Evidence of Alternative Modes of B Cell Activation Involving Acquired Fab Regions of N-Glycosylation in Antibody-Secreting Cells Infiltrating the Labial Salivary Glands of Patients With Sjögren's Syndrome.

To better understand the role of B cells, the potential mechanisms responsible for their aberrant activation, and the production of autoantibodies in the pathogenesis of Sjögren's syndrome (SS), this study explored patterns of selection pressure and sites of N-glycosylation acquired by somatic mutation (acN-glyc) in the IgG variable (V) regions of antibody-secreting cells (ASCs) isolated from the minor salivary glands of patients with SS and non-SS control patients with sicca symptoms. A novel method to produce and characterize recombinant monoclonal antibodies (mAb) from single cell-sorted ASC infiltrates was applied to concurrently probe expressed genes (all heavy- and light-chain isotypes as well as any other gene of interest not related to immunoglobulin) in the labial salivary glands of patients with SS and non-SS controls. V regions were amplified by reverse transcription-polymerase chain reaction, sequenced, and analyzed for the incidence of N-glycosylation and selection pressure. For specificity testing, the amplified regions were expressed as either the native mAb or mutant mAb lacking the acN-glyc motif. Protein modeling was used to demonstrate how even an acN-glyc site outside of the complementarity-determining region could participate in, or inhibit, antigen binding. V-region sequence analyses revealed clonal expansions and evidence of secondary light-chain editing and allelic inclusion, of which neither of the latter two have previously been reported in patients with SS. Increased frequencies of acN-glyc were found in the sequences from patients with SS, and these acN-glyc regions were associated with an increased number of replacement mutations and lowered selection pressure. A clonal set of polyreactive mAb with differential framework region 1 acN-glyc motifs was also identified, and removal of the acN-glyc could nearly abolish binding to autoantigens. These findings support the notion of an alternative mechanism for the selection and proliferation of some autoreactive B cells, involving V-region N-glycosylation, in patients with SS.

Image analysis of fibrosis in labial salivary glands of patients with systemic autoimmune diseases. Close correlation of lobular fibrosis to seropositive rheumatoid arthritis and increased anti-CCP and RF titres in the serum

Lobular fibrosis in labial salivary glands of patients with systemic autoimmune disease is a rarely examined and rather neglected histological change. Its significance and disease association is poorly understood. Our aim was to explore the clinical correlations of fibrosis in labial salivary gland samples using objective methods and laboratory parameters. Labial salivary gland samples from more than 300 patients over a 3-year period were selected from the archives of the pathology department, histologically examined, digitised, image analysed and statistically evaluated to identify the presence and intensity of lobular fibrosis, its relation to age, clinical diagnoses of systemic autoimmune disease and the presence of rheumatoid factor (RF), anti-cyclic citrullinated peptide (CCP), antinuclear antibodies (ANAs), and anti-dsDNA serum markers. Significant correlationwas found between lobular fibrosis and the presence of autoimmune disease (p= 0.023), mainly seropositive rheumatoid arthritis (p < 0.001). Also significant association was found between the fibrosis and the presence of serum anti-CCP (p < 0.001) and IgA/IgG/IgM-RF (p < 0.001, p < 0.001 and p= 0.008, respectively). Significant association was explored between the anti-dsDNA positivity and the negative histology groups (p= 0.033) and between the ANA positivity and the inflammation only group (p= 0.021). The results suggest that lobular fibrosis tends to associate to certain systemic autoimmune diseases, mainly seropositive rheumatoid arthritis, and seems to be rare in labial salivary gland biopsiesof autoimmune diseases characterised by presence of anti-dsDNA. The close correlation of ANA positivity and the inflammation only histology was not surprising, since the majority of patients (62%) have Sjögren's syndrome, known for its inflammatory infiltrate. These findings emphasise that evaluation of lobular fibrosis and inflammation in histological samples of labial salivary gland biopsiesare equally important.

Increased CCL25 and T Helper Cells Expressing CCR9 in the Salivary Glands of Patients With Primary Sjögren's Syndrome: Potential New Axis in Lymphoid Neogenesis.

Follicular helper T (Tfh) cells play a critical role in germinal center formation and B cell activation, both of which are hallmarks of primary Sjögren's syndrome (SS). CCR9-expressing T helper cells have "Tfh-like" characteristics and their numbers are increased at mucosa-associated sites in several inflammatory conditions. Because the characteristics of these cells are unique and evaluation has been limited, this study was undertaken to investigate the local and systemic CCL25/CCR9 axis in patients with primary SS. Levels of CCL25 protein and messenger RNA (mRNA) and CCR9+ T helper cells were evaluated in the labial salivary glands (LSGs) of patients with primary SS and patients with sicca syndrome without a diagnosis of primary SS (non-SS sicca controls). CCL25 levels were assessed for correlation with parameters of inflammation and clinical features. Circulating CCR9+ and CXCR5+ T helper cells were compared on the basis of phenotypic and functional properties. CCL25 protein and mRNA levels were elevated in the LSGs of patients with primary SS as compared to non-SS sicca controls. Increased levels of CCL25 were associated with B cell hyperactivity, autoimmunity, and levels of interleukin-21 (IL-21) and soluble IL-7 receptor α-chain (IL-7Rα). Furthermore, the frequency of CCR9-expressing cells in the LSGs was increased and levels of circulating CCR9+ T helper cells expressing programmed death 1 and inducible T cell costimulator were elevated in patients with primary SS. CCR9+ T helper cells displayed higher expression of IL-7Rα and secreted higher levels of interferon-γ, IL-17, IL-4, and IL-21 as compared to CXCR5+ T helper cells, ex vivo and upon triggering with antigen or IL-7. Both CCR9+ and CXCR5+ T helper cells induced IgG production by B cells more potently than that induced in the cultures with CCR9-CXCR5- T helper cells. Enhanced expression of CCL25 in LSGs of patients with primary SS can facilitate attraction of CCR9+ T helper cells, and these cells secrete high levels of proinflammatory cytokines when triggered with antigen or IL-7. The observed associations with B cell hyperactivity, autoimmunity, and markers of lymphoid neogenesis indicate that the CCL25/CCR9 axis plays a significant role in the immunopathology of primary SS, suggesting that this axis could represent a novel therapeutic target for the disease.

Analysis of the downstream mediators of toll-like receptor 3-induced apoptosis in labial salivary glands in patients with Sjögren's syndrome

Objectives. The aim of this study was to clarify the molecular mechanisms elicited by toll-like receptor (TLR)3 in salivary gland cell death in patients with SS.Methods. Expression of TLR3 and its downstream molecules was examined by immunohistochemical analysis, immunofluorescence, Western blot (WB), and antibody dot-blot array in labial salivary glands (LSGs), and cultured primary salivary gland epithelial cells (SGECs) obtained from patients with SS. We also investigated the difference of expression between ducts/alveoli of LSGs and cultured SGECs.Results. Phosphorylated Fas-associated protein with death domain (p-FADD) or caspase-8 was not found in ducts or alveoli of LSGs from SS patients and controls. Weak expression of receptor-interacting serine/threonine-protein kinase 3 (RIPK3) was found in SS patients, whereas no staining was observed in LSGs of controls. In contrast to LSGs, stimulation of SGECs with polyinosinic:cytidylic acid (poly I:C) significantly induced the expression of RIPK3, p-FADD, and cleaved caspase-8 by immunofluorescence and RIPK3, p-FADD, and cleaved caspase-3 by WB. However, it was counteracted by epidermal growth factor (EGF). Co-localization of anti-apoptotic molecules hemeoxygenase-2, heat shock protein 27, and p-protein kinase B or p-Akt was induced in EGF-stimulated SGECs.Conclusions. We observed that poly I:C induced apoptosis of SGECs in vitro compared with a relatively low prevalence of apoptosis found in the ducts and alveoli of LSGs in vivo. Thus, we speculate that other counter-regulatory mechanisms, including those induced by EGF, might exist to protect against TLR3-mediated apoptosis of ductal and acinar epithelial cells in vivo.

Stereotypic rheumatoid factors that are frequently expressed in mucosa-associated lymphoid tissue-type lymphomas are rare in the labial salivary glands of patients with Sjögren's syndrome.

Among autoimmune diseases, Sjögren's syndrome (SS) is most strongly associated with the development of malignant B cell lymphoma, in particular mucosa-associated lymphoid tissue (MALT)-type lymphoma. Previously, we have shown that in ∼40% of cases of salivary gland MALT lymphoma, high-affinity stereotypic rheumatoid factor (RF) B cell receptors, specific for IgG-Fc, are expressed. This study was undertaken to investigate whether in the inflamed salivary glands of patients with SS, a similar RF-biased Ig repertoire is present. Extensive analyses of the B cell Ig VH region repertoire were performed on microdissected tissue samples from the labial salivary glands of 4 patients with SS. All SS labial salivary glands harbored expanded B cell clones, of which 1 or 2 were highly expanded and detected in >50% of the microdissected samples. However, among the identified 464 distinct Ig clonotypes, only 3 stereotypic RF-expressing clones were detected. In 2 patients with SS, an RF-expressing clone was detected at low frequency in 1 of the microdissected samples, whereas 1 patient with SS harbored a highly expanded RF-expressing clone that was detected in all microdissected samples and also detected in the peripheral blood. Two years after analysis of this sample, the latter patient developed a diffuse large B cell lymphoma originating from the same RF clone. Inflamed labial salivary glands in patients with SS generally harbor 1 or 2 highly expanded B cell clones. The repertoire strongly biased toward stereotypic RFs in salivary gland MALT lymphomas is not a reflection of a similar repertoire in the inflamed salivary glands of patients with SS; rather, in the latter, the repertoire is based on a strong selection advantage of incidental stereotypic RF-expressing B cells.

Autoantibodies against interferon-γ reduce the frequency of pulmonary fibrosis and concentration of C-reactive protein in patients with primary Sjögren's syndrome

Primary Sjögren's syndrome (pSS) is a prototypic autoimmune disease characterized by immune injury to the salivary and lacrimal glands. In addition, some patients with pSS develop several systemic complications, such as renal, pulmonary or neurological manifestations. The establishment of type I interferons (IFN) pathway designates pSS an autoimmune disease characterized by an “IFN-signature” [1], but type II IFN, IFN-γ, also participates in the pathogenesis of pSS. Expression of high levels of IFN-γ mRNA and serum IFN-γ is found in conjunctiva and labial salivary glands in patients with pSS and correlates with degree of T-cell infiltration [2–4]. In animal models, high levels of IFN-γ can be detected in NOD/ShiLtJ and NOD-derived congenic C57BL/6.NOD-Aec1Aec2 mice newborned [5,6]. High production of IFN-γ was also found in muscarinic type 3 receptor−/− (M3R−/−) mice treated with free-form extracellular peptides of M3R [7]. IFN-γ-producing M3R-reactive T cells play a crucial role in the generation of SS-like sialadenitis via the induction of apoptosis [8]. However, few studies have been performed on the anti-IFN-γ autoantibodies (aAbs) in patients with pSS.

AB0128 Expression of aberrantly glycosylated mucins (tn and sialyl tn antigens) and muc1 in labial salivary gland of patients with sjogren’s syndrome.

BackgroundPrimary Sjogren syndrome (SS) is an autoimmune exocrinopathy. Mucin are present on apical surfaces of all healthy wet surface epithelia of human body and on the glands of simple secretory...

FRI0258 Decreased tslp expression in labial salivary glands of patients with primary sjögren’s syndrome is associated with increased t and b cell inflammation and tissue destruction

BackgroundThymic Stromal Lymphopoietin (TSLP) is a potent immunomodulatory cytokine involved in Th2-mediated immune responses and homeostatic T-cell expansion. Reduced TSLP expression by intestinal epithelial cells was recently shown to lead...

SAT0172 Decreased expression of thymic stromal lymphopoietin in labial salivary glands of patients with primary sjögren’s syndrome is associated with local and systemic disease parameters

BackgroundThymic Stromal Lymphopoietin (TSLP) is a potent immunomodulatory IL-7 related cytokine involved in Th2 mediated immune responses and homeostatic T-cell expansion. Reduced TSLP expression by intestinal epithelial cells was recently...

Decreased expression of TSLP in labial salivary glands of patients with primary Sjögren’s syndrome is associated with local- and systemic disease parameters

Background Thymic Stromal Lymphopoietin (TSLP) is a potent immunomodulatory cytokine involved in Th2-mediated immune responses and homeostatic T-cell expansion. Reduced TSLP expression by intestinal epithelial cells was recently shown to lead to reduced Th2 responses and development of Th1-mediated experimental colitis. Additionally, TSLP is described as a proinflammatory factor in autoimmune diseases. TSLP expression was studied in salivary glands of primary Sjogren’s syndrome (pSS) patients as compared to non-SS Sicca (nSS) patients and the relationship to localand systemic disease parameters was examined.

Detection of HTLV-1 in the Labial Salivary Glands of Patients with Sjögren’s Syndrome: A Distinct Clinical Subgroup?

To examine whether patients with Sjögren's syndrome (SS) can be distinguished based on the expression of human T cell lymphotrophic virus type I (HTLV-1) and, if so, whether the subgroups differ in their clinical features and serological measures. Polymerase chain reaction (PCR) and nested PCR were used to amplify viral DNA from peripheral blood mononuclear cells (PBMC) in 53 patients with SS, using primers from the HTLV-1 pX, p19, pol, and tax regions. Minor salivary gland biopsy specimens from 33 patients with SS were examined for the presence of HTLV-1 p19 or tax proteins immunohistochemically. The sociodemographic, glandular, and extraglandular manifestations, and laboratory findings including autoantibodies, complement, and immunoglobulin levels, were analyzed. The HTLV-1 tax gene was detected in PBMC samples from 2 of 53 patients (3.8%), whereas the HTLV-1 pX, p19, and pol genes were not expressed. As well, 100% of PBMC samples from 4 family members of patients in whom the tax gene was detected also expressed the tax gene. Immunohistochemical staining for HTLV-1 p19 and tax was seen in 10 out of 33 (30.3%) patients with SS each. Overall, 14 (42.4%) patients expressed HTLV-1 p19 or tax proteins, and they had lower rheumatoid factor and C3 levels (p = 0.015 and p = 0.005, respectively) and higher lymphocyte counts (p = 0.016). The prevalence of glandular and extraglandular manifestations did not differ between the HTLV-1-positive and negative patients. Our findings suggest that HTLV-1 in the salivary glands is involved in the pathogenesis of a subpopulation of SS, and HTLV-1-associated SS might have different immunological patterns than idiopathic SS.

Increased interleukin (IL)-7Rα expression in salivary glands of patients with primary Sjögren's syndrome is restricted to T cells and correlates with IL-7 expression, lymphocyte numbers and activity

ObjectiveTo identify interleukin (IL)-7Rα expression in the labial salivary gland (LSG) of patients with primary Sjögren's syndrome (pSS) and non-Sjögren's syndrome sicca (nSS-sicca) and to study its correlation with glandular...