| ObjectiveSj?gren’s syndrome(SS)is an autoimmune disease characterized with lymphocyte infiltration in the salivary gland and lacrimal gland tissues,leading to chronic inflammatory responses and causing the symptoms such as dry eye and dry mouth.However the etiology and pathogenesis of SS is unclear.There is a growing evidence that apoptosis of exocrine glandular epithelial cells play an important role in the pathogenesis of Sjogren’s syndrome.In addition,the balance of Bcl-2 and Bax in these cells of SS may explain their inclination to apoptosis.Epithelial cell adhesion factor(EpCAM)can promote apoptosis by downregulating the expression of the anti-apoptotic protein Bcl-2 and upregulating the expression of the pro-apoptotic proteins Bax.EpCAM is an type-I single-span transmembrane glycoprotein consisting of an extracellular domain(EpEX)with a epidermal growth factor and a thyroglobulin-like domain,a transmembrane domain,and an intracellular(Ep ICD)with 26 amino acid,which is present in most of the epithelial cells in adults.The aim of this study was to investigate the expression of EpCAM in the gland of SS and its clinical significance,and further explore its role in the pathogenesis of SS.Method:57 cases of SS patients and 25 cases of normal control group were enrolled from the Department of Immunology in the xijing hospital from March 2013 to May 2016.All patients was conducted the salivary gland biopsy.Immunohistochemical staining was used to detect the expression of EpCAM and Ep ICD,and to analyze the correlation between them with the clinical indicators.The expression of EpCAM and EpICD and its corresponding cell’s proliferation Level was detected by flow cytometry after apoptosis of human umbilical vein endothelial cells induced by tumor necrosis factor α.Statistical analysis was performed using Mann-Whitney U test,ANOVA single factor multivariate analysis,pearson correlation analysis and spearman correlation analysis.P <0.05 for the difference was statistically significant.Result:1.EpCAM was highly expressed in the membrane of the control group and EpICD was highly expressed in the cytoplasm.While the expression of EpCAM in cell membrane is decreased in the SS patients and in accordance with the severity of the disease(P<0.01),while the expression of Ep ICD in the cytoplasm is increased(P<0.01).And the morphological changes of the salivary glands were more prominent.2.EpCAM staining of membrance was significantly correlated with the results of schirmer’s test(P<0.05)and anti-SSA(NS vs 2+,P<0.05;NS vs 3+,P<0.01).Ep ICD cytoplasmic staining is correlated with anti-SSA(NS vs 3+,P<0.05)and RF(P<0.05).The expression of EpCAM and EpICD staining was significantly correlated with the course of disease(P <0.05),dry mouth(P<0.05)and rampant caries(P<0.05),but their relation with dry eye,parotid gland enlargement,ESR,CRP,anti-SSB,Anti-Ro52,antinuclear antibody,IgA,Ig G,IgM,C3,C4,RF were not statistically significant.3.The cut-off value of EpCAM is 3.135.The sensitivity is 93.9% and the specificity is 90%.The cut-off value of Ep ICD in the cytoplasm was 3.795.The sensitivity was 78.8% and the specificity was 100%.4.Ihe proliferation capacity of endothelial cells reduce after induction of apoptosis,and the expression of Ep CAM is dropped and EpICD expression is increased.Conclusion:1.With the exacerbation of SS,the expression of EpCAM is decreased and the expression of EpICD is increased.2.The expression of Ep CAM/EpICD was correlated with xerostomia,saprodontia,duration,anti-SSA antibody and histopathological grade of the labial gland.It was not proved that it is related to the other serological examination and clinical symptoms.3.EpCAM/EpICD is better than some serological examinations in terms of diagnosis and can effectively assess the severity of SS disease.More importantly it provide new ideas for the early diagnosis and treatment of SS.4.EpCAM / Ep ICD is involved in the process of cell proliferation and apoptosis in SS,which provides a new direction for the study of SS pathogenesis. |
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