Dataset Information

Elevated CCL19/CCR7 Expression During the Disease Process of Primary Sjogren's Syndrome.

ABSTRACT: Primary Sjögren's syndrome (pSS) is a common chronic autoimmune disease characterized by a high prevalence of autoantibodies and lymphocyte-mediated exocrine gland damage. To enhance our understanding of the mechanisms underlying the progression of the disease and to discover potential biomarkers for the early diagnosis of pSS, we applied RNA sequencing to compare the gene expression patterns in minor salivary glands between pSS patients and non-pSS. A total of 293 differentially expressed genes (DEGs) were detected in pSS vs. non-pSS (FDR < 0.05, fold changes > 2). Of these DEGs, 285 (97.26%) were up-regulated, with most being involved in immune system activation, especially in the formation of the immunological synapse. Significantly elevated CCL19/CCR7 expression in the salivary gland was found to be related to anti-Sjögren's syndrome-related antigen A (SSA) antibody and IgG levels in pSS patients, which was further confirmed in a larger cohort. Up-regulated gene expression showed strong discriminatory accuracy in identifying pSS with area under the curve of 0.98 using receiver operating characteristic curve analysis. In conclusion, gene expression changes in pSS include strong markers of immunological activation and have good discriminatory power in identifying patients with pSS.

SUBMITTER: Liu Z

PROVIDER: S-EPMC6491632 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Elevated <i>CCL19</i>/<i>CCR7</i> Expression During the Disease Process of Primary Sjögren's Syndrome.

Liu Zhenwei Z Li Fengxia F Pan Axiao A Xue Huangqi H Jiang Shan S Zhu Chengwei C Jin Mengmeng M Fang Jinxia J Zhu Xiaochun X Brown Matthew A MA Wang Xiaobing X

Frontiers in immunology 20190424

Primary Sjögren's syndrome (pSS) is a common chronic autoimmune disease characterized by a high prevalence of autoantibodies and lymphocyte-mediated exocrine gland damage. To enhance our understanding of the mechanisms underlying the progression of the disease and to discover potential biomarkers for the early diagnosis of pSS, we applied RNA sequencing to compare the gene expression patterns in minor salivary glands between pSS patients and non-pSS. A total of 293 differentially expressed genes ...[more]

PMID: 31068931

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Project description:Background Interstitial lung disease (ILD) may cause life-threatening complications of primary Sjogren’s syndrome (pSS), and has a poor prognosis in terms of survival and quality of life. To date, few studies have investigated the risk factors for ILD detected by high-resolution computed tomography (HRCT) in pSS patients with or without respiratory symptoms. Methods Data of 333 patients with newly diagnosed pSS were retrospectively analysed. Interstitial lung disease involvement was defined as typical abnormalities on HRCT and/or pulmonary function tests. Multivariate regression model was used to evaluate the association between interstitial lung disease and pSS characteristics. Results Sixty-six patients (19.82%) were diagnosed with pSS-ILD. Ground glass opacities (87.88%) and septal/sub pleural lines (81.82%) were most frequent. Based on pulmonary high-resolution computed tomography, patients were divided into nonspecific (n = 42), usual (n = 20), lymphocytic interstitial pneumonia (n = 3) and cryptogenic organising pneumonia (n = 1) groups. There was a strong association between erythrocyte sedimentation rate (ESR)/C-reactive protein (CRP) and the HRCT-score. Pulmonary function tests revealed impaired diffusion capacity for carbon monoxide and total lung capacity, and coexistence of small airway lesions in pSS-interstitial lung disease. On logistic regression analysis, age, Raynaud’s phenomenon, lymphopenia, cough, dyspnoea and rampant dental caries were risk factors associated with pSS-interstitial lung disease. Conclusions Interstitial lung disease involvement in pSS is a common clinical occurrence. The clinical manifestation is nonspecific and variable; Raynaud’s phenomenon and lymphopenia may predict its onset. pSS patients with advanced age, dry cough and dyspnoea should be systematically evaluated for ILD involvement and managed according to their symptoms. Supplementary Information The online version contains supplementary material available at 10.1186/s12890-022-01868-5.

Project description:Objectives The aim of this study was to investigate serum biomarkers linked to primary Sjögren's syndrome (pSS)-associated interstitial lung disease (ILD). Methods 69 pSS patients were consecutively enrolled and evaluated via quantitative ILD scoring based on high-resolution computed tomography (HRCT). Biomarkers of interest were assessed by multiplex enzyme-linked immunosorbent assays (ELISAs). Results Among consecutively enrolled patients with pSS, the presence of pSS–ILD was 50% based on the presence of radiographically defined interstitial lung abnormalities (ILA) meeting specified criteria for mild/moderate (ILA 2) or severe (ILA 3) disease. Age, immunoglobulin M (IgM), C-reactive protein (CRP), and serum levels of eotaxin/CCL11, Krebs von den Lungen-6 (KL-6), TNFα, and TGFα were significantly higher in the combined pSS–ILD group (ILA 2 + ILA 3) than in the pSS–no-ILD and pSS–indeterminate ILD groups (ILA 0 and ILA 1, respectively) in unadjusted analyses (p < 0.05 for all variables). A binary logistic regression model revealed that disease duration and KL-6 levels were associated with the presence of pSS–ILD (p < 0.05). Complementary least absolute shrinkage and selection operator (LASSO) modeling showed that age, KL-6, and TNF-α effectively differentiated pSS–ILD (ILA 2 + ILA3) from pSS without ILD (ILA 0 + ILA 1), with an area under the curve (AUC) of 0.883 (p value < 0.0001). Conclusions Patient age, disease duration, and serum levels of both KL-6 and TNFα were the most discriminating factors associated with the presence of ILD in our pSS patients. Higher levels of CRP, IgM, eotaxin, TGFα, and TNFα should also prompt the search for occult as well as clinically evident lung involvement based on statistically significant univariate associations with pSS–ILD. Clinical trial registration None. Supplementary Information The online version contains supplementary material available at 10.1186/s40001-022-00828-3.

Dataset Information

Elevated CCL19/CCR7 Expression During the Disease Process of Primary Sjogren's Syndrome.

Publications

Elevated <i>CCL19</i>/<i>CCR7</i> Expression During the Disease Process of Primary Sjögren's Syndrome.

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