ABSTRACT
Sjögren's syndrome (SS) is an autoimmune disease characterized by periductal lymphocytic infiltration of the salivary and lacrimal glands. SS also exhibits extra-glandular manifestations and specific autoantibodies. Salivary gland ultrasonography (SGUS) is a common procedure used to assess the severity of glandular involvement. However, the association between SGUS and extra-glandular lesions remains poorly understood. This study aimed to identify clinical indices, including disease activity, associated with glandular involvement using SGUS in patients with SS. We included 115 patients with SS and 90 without SS. Patients with SS had significantly higher ultrasonography (US) score than patients without SS. Multivariate analysis revealed focus score, Saxon test positivity, and anti-centromere antibody (ACA) positivity as independent variables associated with the US score in patients with SS. In addition, these results were similar to those obtained in patients with primary SS. Patients with SS and ACA positivity had higher US score and an increased prevalence of hyperechoic bands in the parotid glands and submandibular glands. In conclusion, this study indicated that ACA positivity is associated with the US score in patients with SS. These results suggest that US findings in patients with ACA positivity might show specific changes in the salivary glands, especially fibrosis.
Subject(s)
Autoimmune Diseases , Sjogren's Syndrome , Humans , Sjogren's Syndrome/diagnostic imaging , Salivary Glands/diagnostic imaging , Parotid Gland/diagnostic imaging , UltrasonographyABSTRACT
Sjögren's syndrome (SS) is a rheumatic disease characterized by sicca and extraglandular symptoms, such as interstitial lung disease and renal tubular acidosis. SS potentially affects the prognosis of patients, especially in cases of complicated extraglandular symptoms; however, only symptomatic therapies against xerophthalmia and xerostomia are currently included in the practice guidelines as recommended therapies for SS. Considering that SS is presumed to be a multifactorial entity caused by genetic and environmental factors, a multidisciplinary approach is necessary to clarify the whole picture of its pathogenesis and to develop disease-specific therapies for SS. This review discusses past achievements and future prospects for pursuing the pathophysiology and therapeutic targets for SS, especially from the perspectives of viral infections, toll-like receptors (TLRs), long-noncoding RNAs (lncRNAs), and related signals. Based on the emerging roles of viral infections, TLRs, long-noncoding RNAs and related signals, antiviral therapy, hydroxychloroquine, and vitamin D may lower the risk of or mitigate SS. Janus-kinase (JAK) inhibitors are also potential novel therapeutic options for several rheumatic diseases involving the JAK-signal transducer and activator of transcription pathways, which are yet to be ascertained in a randomized controlled study targeting SS.
ABSTRACT
OBJECTIVE: To investigate whether stimulation with toll-like receptor (TLR) 7 leads to pathways that proceed to tripartite motif-containing protein 21 (TRIM21) or Ro52/SS-A antigen presentation through major histocompatibility complex (MHC) class I in salivary gland epithelial cells (SGECs) from Sjögren's syndrome (SS) patients. DESIGN AND METHODS: Cultured SGECs from SS patients were stimulated with TLR7 agonist, loxoribine, and interferon-ß. Cell lysates immunoprecipitated by anti-MHC class I antibody were analyzed by Western blotting. The immunofluorescence of salivary gland tissue from SS and non-SS subjects and cultured TLR7-stimulated SGECs was examined. RESULTS: Significantly increased MHC class I expression was observed in SS patients' ducts versus non-SS ducts; no significant difference was detected for ubiquitin. Upregulated MHC class I in the cell membrane and cytoplasm and augmented Ro52 expression were observed in SGECs stimulated with TLR7. The formation of peptide-loading complex (PLC), including tapasin, calreticulin, transporter associated with antigen processing 1, and endoplasmic reticulum-resident protein 57 in labial salivary glands (LSGs) from SS patients, was dominantly observed and colocalized with MHC class I, which was confirmed in TLR7-stimulated SGEC samples. CONCLUSION: These findings suggest that the TLR7 stimulation of SS patients' SGECs advances the process toward the antigen presentation of TRIM21/Ro52-SS-A via MHC class I.
ABSTRACT
Background: The relationship between anti-Ro52/SS-A antibody (anti-Ro52) and the clinical manifestations of Sjögren's syndrome (SS) has not been fully clarified. We determined the clinical factors relevant to SS patients with anti-Ro52.Methods: We conducted a retrospective study of 149 subjects suspicious for SS and 50 healthy control subjects. We analyzed items of the American-European Consensus Group (AECG) criteria and the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI).Results: SS was documented in 115 subjects. Anti-Ro52 was observed in 70 SS patients. Anti-Ro52 positivity showed a significantly higher association with anti-Ro60 positivity than with anti-centromere antibody (ACA) positivity (p < 0.05). Regarding the difference in the anti-Ro52 concentration, we observed six significantly relevant components: two AECG components and four non-AECG components. The anti-Ro52 concentration well-discriminated three clinical factors (ROC AUC >0.75), i.e., ACA seropositivity, ESSDAI score ≥1, and RF, and it moderately discriminated high serum IgG, focus score ≥1, and anti-La/SS-B antibody seropositivity (ROC AUC >0.7). A linear relationship between the ESSDAI score and the anti-Ro52 concentration was observed.Conclusion: A significant association between clinical factors (including the ESSDAI) and the anti-Ro52 concentration were revealed. Anti-Ro52 was more highly associated with anti-Ro60 positivity than with ACA positivity.
Subject(s)
Sjogren's Syndrome , Antibodies, Antinuclear , Humans , Retrospective Studies , Sjogren's Syndrome/diagnosisABSTRACT
INTRODUCTION: The 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). METHODS: We 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. RESULTS: Among 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. CONCLUSIONS: HTLV-1 partially inhibited the BAFF and CXCL13 expressions of established FDC-like cells.