Dataset Information

Gene Expression Profiles in Primary Sjogren's Syndrome With and Without Systemic Manifestations.

ABSTRACT: Objective:To investigate the gene expression profile in patients with Sjögren's syndrome that is characterized by different clinical phenotypes. Methods:RNA from peripheral blood mononuclear cells was purified in 8 patients with glandular features (GFs) and widespread pain (WP) and 11 with extraglandular manifestations (EGMs) and then was analyzed by hybridization on a human gene chip exploring more than 40,000 human genes. Differentially expressed genes (DEGs) in the two subgroups (ie, those with false discovery rate-corrected P values ? 0.01) with respect to 20 healthy controls have been submitted to functional classification using a Gene Ontology database and were mapped to define the networks of protein to protein interactions (PPIs). Results:The enriched pathway analyses of DEGs and of the highly interconnected modules identified in the PPI networks showed that the pathological processes characterizing the two subgroups were substantially different. The predominant pathways in patients with EGMs are related to T- and B-cell activation, Toll-like receptor, interferon signaling, and apoptosis. Conversely, pathological processes related to pain transmission and modulation are preferentially operative in patients with GFs and WP. These data suggest that a neuroinflammatory pathway driven by cytokines and chemokines may play a central role in triggering WP features in this phenotype of patients. Conclusion:The present study supports the hypothesis that different biological pathways are operative in patients with primary Sjögren's syndrome with different clinical phenotypes. A better knowledge of these specific processes might help in tailoring more effective target therapies.

SUBMITTER: Vitali C

PROVIDER: S-EPMC6917337 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Gene Expression Profiles in Primary Sjögren's Syndrome With and Without Systemic Manifestations.

Vitali Claudio C Dolcino Marzia M Del Papa Nicoletta N Minniti Antonina A Pignataro Francesca F Maglione Wanda W Lunardi Claudio C Puccetti Antonio A

ACR open rheumatology 20191021 10

<h4>Objective</h4>To investigate the gene expression profile in patients with Sjögren's syndrome that is characterized by different clinical phenotypes.<h4>Methods</h4>RNA from peripheral blood mononuclear cells was purified in 8 patients with glandular features (GFs) and widespread pain (WP) and 11 with extraglandular manifestations (EGMs) and then was analyzed by hybridization on a human gene chip exploring more than 40,000 human genes. Differentially expressed genes (DEGs) in the two subgroup ...[more]

PMID: 31872181

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Project description:IntroductionSjögren's syndrome (SS) is a systemic autoimmune disease that mainly targets the exocrine glands. The aim of this study was to investigate the involvement of 87 proteins measured in serum and 75 proteins analyzed in saliva in spontaneous experimental SS. In addition, we intended to compute a model of the immunological situation representing the overt disease stage of SS.MethodsNondiabetic, nonobese diabetic (NOD) mice aged 21 weeks were evaluated for salivary gland function, salivary gland inflammation and extraglandular disease manifestations. The analytes, comprising chemokines, cytokines, growth factors, autoantibodies and other biomarkers, were quantified using multi-analyte profile technology and fluorescence-activated cell sorting. Age-matched and sex-matched Balb/c mice served as a reference.ResultsWe found NOD mice to exhibit impaired salivary flow, glandular inflammation and increased secretory SSB (anti-La) levels. Thirty-eight biomarkers in serum and 34 in saliva obtained from NOD mice were significantly different from those in Balb/c mice. Eighteen biomarkers in serum and three chemokines measured in saliva could predict strain membership with 80% to 100% accuracy. Factor analyses identified principal components mostly correlating with one clinical aspect of SS and having distinct associations with components extracted from other families of proteins.ConclusionAutoimmune manifestations of SS are greatly independent and associated with various immunological processes. However, CD40, CD40 ligand, IL-18, granulocyte chemotactic protein-2 and anti-muscarinic M3 receptor IgG3 may connect the different aspects of SS. Processes related to the adaptive immune system appear to promote SS with a strong involvement of T-helper-2 related proteins in hyposalivation. This approach further established saliva as an attractive biofluid for biomarker analyses in SS and provides a basis for the comparison and selection of potential drug targets and diagnostic markers.

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Dataset Information

Gene Expression Profiles in Primary Sjogren's Syndrome With and Without Systemic Manifestations.

Publications

Gene Expression Profiles in Primary Sjögren's Syndrome With and Without Systemic Manifestations.

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