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Epithelial Cell Adhesion Molecule in Primary Sjogren's Syndrome Patients: Characterization and Evaluation of a Potential Biomarker.

ABSTRACT: Objective:To determine the subcellular localization of epithelial cell adhesion molecule (EpCAM) in labial salivary gland (LSG) and evaluate the diagnostic use of the extracellular domain of EpCAM (EpEX) and intracellular domain (EpICD) for primary Sjögren's syndrome (pSS). Methods:Immunohistochemical (IHC) analysis was conducted using EpEX and EpICD domain-specific antibodies on labial salivary gland biopsy (LSGB) from participants. Chi-square or Fisher's exact analysis, Mann-Whitney U-test, and Kruskal-Wallis test compared differences among groups. Independent risk factors of pSS were determined by multiple logistic regression analysis. Receiver-operator characteristic curves (ROC) were carried out to estimate the diagnostic value. Results:Compared to non-SS controls, loss of membranous EpEX and EpICD expression was observed in LSGB of pSS patients, which occurred in parallel with increased accumulation of cytoplastic and nuclear EpICD. The subcellular EpEX/EpICD expressions were associated with various features of pSS patients, especially histopathological grade of LSGB. Furthermore, high IHC scores of membranous EpEX were independent risk factors for pSS, even for the pSS patients at early stage. The IHC scores of subcellular EpEX/EpICD were of great diagnostic value for pSS with high sensitivity (70-80%) and specificity (85-95%). Conclusion:This study first found the aberrant expression pattern of EpCAM in LSG of pSS patients. The IHC scores of subcellular EpEX/EpICD were demonstrated to have the potential to act as diagnostic biomarkers for pSS.

SUBMITTER: Zhang K

PROVIDER: S-EPMC6915146 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Epithelial Cell Adhesion Molecule in Primary Sjögren's Syndrome Patients: Characterization and Evaluation of a Potential Biomarker.

Zhang Kui K Zhou Yaxin Y Cheng Xiaojing X Fu Xianghui X Du Wanglei W Feng Yuan Y Jia Junfeng J Yang Xichao X Xiao Guangzhi G Zheng Zhaohui Z Zhu Ping P Wu Zhenbiao Z

Journal of immunology research 20191205

<h4>Objective</h4>To determine the subcellular localization of epithelial cell adhesion molecule (EpCAM) in labial salivary gland (LSG) and evaluate the diagnostic use of the extracellular domain of EpCAM (EpEX) and intracellular domain (EpICD) for primary Sjögren's syndrome (pSS).<h4>Methods</h4>Immunohistochemical (IHC) analysis was conducted using EpEX and EpICD domain-specific antibodies on labial salivary gland biopsy (LSGB) from participants. Chi-square or Fisher's exact analysis, Mann-Whi ...[more]

PMID: 31886299

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Project description:BackgroundPrimary Sjögren's syndrome (pSS) is an autoimmune condition that causes harm to exocrine glands and also has extra-glandular manifestations (EGM). pSS patients with EGM have a worse prognosis than those with only sicca symptoms. Previous studies have shown that the minor salivary glands (MSG) of pSS patients exhibit a unique profile of cytokines and chemokines compared to healthy controls. However, there is a lack of research comparing pSS with EGM (pSS-EGM) and pSS without EGM (pSS-non-EGM). This study aims to explore potential biomarkers associated with pSS, particularly pSS with EGM.MethodsBy utilizing RNA sequencing, we conducted an analysis on the gene expression profiles of MSG in 63 patients diagnosed with pSS, as well as 12 non-pSS individuals. Furthermore, we also investigated the MSG of pSS patients, both with and without EGM. Through bioinformatics analysis, we identified genes with differential expression (DEGs) and determined the core hub genes using PPI network. We then analyzed the top 20 DEGs and their correlation with the patients' clinical characteristics, and validated our findings using peripheral blood plasma.ResultsA total of 725 differentially expressed genes (DEGs) were identified in the comparison between pSS and non-pSS groups, and 727 DEGs were observed between pSS-EGM and pSS-non-EGM. It is noteworthy that the expression levels of CXCL9 were higher in both pSS patients and pSS-EGM when compared to the control group. Taking into consideration the significance of the top 20 DEGs in relation to clinical parameters and the central hub genes, we ultimately chose CXCL9. In comparison to the non-pSS group, pSS patients exhibited notably greater expression of the CXCL9 gene in the MSG, as well as higher levels of CXCL9 protein in their plasma (p < 0.001). Furthermore, the expression of the CXCL9 gene and levels of CXCL9 protein were notably higher in pSS patients accompanied by EGM and those with SSA antibodies. Additionally, a correlation was found between the expression of the CXCL9 gene and the EULAR Sjogren's Syndrome Disease Activity Index (ESSDAI), as well as with immunoglobulin G (IgG) levels and erythrocyte sedimentation rate (ESR). Meanwhile, the protein levels of CXCL9 were found to be correlated with IgG levels and ESSDAI.ConclusionCXCL9 proves to be a valuable biomarker in pSS, specifically due to its strong ability to differentiate between pSS patients with EGM and those without EGM. There is a significant correlation between CXCL9 and various clinical parameters both at the gene and protein level. Therefore, CXCL9 could be a potential target for future treatment of pSS.

Project description:BackgroundDry eye is often the first presenting manifestation of primary Sjögren's syndrome (pSS). Because of the high prevalence of dry eye disease in normal population, ophthalmologists urgently need a non-invasive and reliable screening test to diagnose dry eye associated SS patients, other than ocular symptoms and signs. Currently, there is no single test available. The correlation of serum IL-14α with pSS has been found in pSS mouse model.PurposeTo evaluate whether IL-14α can serve as a biomarker to stratify dry eye in primary Sjögren's syndrome and its correlation to BAFF in a cohort of patients with non-SS dry eye (NSDE), pSS with dry eye disease, rheumatoid arthritis (RA), and healthy controls (HC).MethodsRetrospective study based on serum levels of IL-14α (defined by Western Blot) and BAFF (measured by ELISA) were evaluated among pSS with dry eye disease, NSDE, RA, and HC groups. Serum levels of SS related autoantibodies (Ro, La, SP1, PSP, and CA6) were also measured by ELISA.ResultsOne hundred and eighty patients were included for the current study, patients were separated into four groups as defined by pSS (n=65), NSDE (n=20), RA (n=50) and HC (n=45). The level of serum IL-14α in pSS was significantly higher compared to NSDE, RA, and HC (p=0.0011, p=0.0052 and p<0.0001, respectively). The levels of serum BAFF in pSS was significantly higher than in NSDE and HC (p=0.0148 and p<0.0001, respectively, whereas the levels of serum BAFF in RA was only significantly higher than in HC (p=0.001), but the level of BAFF was no significant difference between pSS and RA. In pSS, there was a decrease in the serum levels of IL-14α associated with a longer duration of the disease. Also, there was a correlation between the serum levels of IL-14α and SS related autoantibodies such as anti-SSA/Ro and anti-SSB/La in pSS patients.ConclusionsThis is the first paper to report both IL-14α and BAFF could serve as a critical cytokine biomarker for the stratification of dry eye in primary Sjögren's syndrome. This may help ophthalmologists to develop non-invasive metrics for the diagnosis of dry eye associated pSS.

Dataset Information

Epithelial Cell Adhesion Molecule in Primary Sjogren's Syndrome Patients: Characterization and Evaluation of a Potential Biomarker.

Publications

Epithelial Cell Adhesion Molecule in Primary Sjögren's Syndrome Patients: Characterization and Evaluation of a Potential Biomarker.

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