Development Of pSS Research Articles

Identification of immune-related diagnostic markers in primary Sjögren's syndrome based on bioinformatics analysis.

BackgroundPrimary Sjögren’s syndrome (pSS) is a relatively common diffuse connective tissue disease that often invades exocrine glands, such as the lacrimal and salivary glands, and manifests as dry eyes and dry mouth. At present, the molecular mechanism of pSS is not clear. This study was designed to explore the internal mechanism of pSS from the gene level and screen out the immune-related diagnostic markers of pSS.MethodsThe gene expression profiles GSE84844, GSE7451, and GSE40611 were downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified with R software. Then, the DEGs were intersected with the immune genes obtained from the ImmPort database to acquire differentially expressed immune-related genes (DEIRGs), and functional enrichment analyses were performed. The DEIRGs were screened through the least absolute shrinkage and selection operator (LASSO) logistic regression algorithm to obtain the optimal immune-related genes (IRGs). Expression levels of the optimal IRGs were verified by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) to obtain the key genes. Next, gene chips GSE7451 and GSE40611, from other tissues, were selected as the training sets to verify the sensitivity and specificity of the diagnosis of the key genes by receiver operating characteristic (ROC) analysis.ResultsA total of 54 DEIRGs were obtained. The functional enrichment analysis results showed that they play an important role in immune and inflammatory responses. Nine optimal IRGs were screened from the DEIRGs by the LASSO logistic regression algorithm. After qRT-PCR verification, eight out of nine optimal IRGs (IL-18, JAK2, TBK1, EED, TNFSF10, TNFSF13B, CYSLTR1, and ICOS) were significantly highly expressed in pSS patients and were defined as key genes. ROC analysis identified that TNFSF13B and CYSLTR1 had high sensitivity and specificity. Finally, the lack of previous research on EED and CYSLTR1 in pSS suggests that these IRGs may be regarded as new gateways to explore the diagnosis and pathogenesis of pSS.ConclusionsThe key DEIRGs play a decisive role during the occurrence and development of pSS.

ICOS Gene Polymorphisms (IVS1 + 173 T/C and c. 1624 C/T) in Primary Sjögren's Syndrome Patients: Analysis of ICOS Expression.

Background: Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disease, which affects exocrine glands. T cell activation is a trigger mechanism in the immune response. Hyperreactivity of T cells and antibody production are features in pSS. ICOS can be critical in the pathogenesis of pSS. Methods: A total of 134 pSS patients and 134 control subjects (CS) were included. Genotyping was performed by PCR-RFLP. ICOS mRNA expression was quantified by real-time PCR, and CD4+ ICOS+ T cells were determined by flow cytometry. Results: The ICOS IVS1 + 173 T>C polymorphisms were not associated with susceptibility to pSS (p = 0.393, CI = 0.503–1.311). However, the c.1624 C>T polymorphism was associated with a reduction in the risk of development of pSS (p = 0.015, CI = 0.294–0.884). An increase in ICOS mRNA expression in patients was observed (3.7-fold). Furthermore, pSS patients showed an increase in membranal-ICOS expression (mICOS). High expression of mICOS (MFI) was associated with lymphocytic infiltration. Conclusions: The IVS1 + 173 polymorphism is not a genetic marker for the development of pSS, while c.1624 T allele was associated with a low risk. However, elevated mICOS expression in pSS patients with high lymphocytic infiltration was found. ICOS may have an important role in the immunopathogenesis of pSS and should be analyzed in T cell subsets in pSS patients as a possible disease marker.

Novel Immune-Related Genetic Expression for Primary Sjögren's Syndrome

Objective: To identify novel immune-related genes expressed in primary Sjögren's syndrome (pSS).Methods: Gene expression profiles were obtained from the Gene Expression Omnibus (GEO) database, and differentially expressed genes (DEGs) were screened. The differences in immune cell proportion between normal and diseased tissues were compared, weighted gene co-expression network analysis was conducted to identify key modules, followed by a protein–protein interaction (PPI) network generation and enrichment analysis. The feature genes were screened and verified using the GEO datasets and quantitative real-time PCR (RT-qPCR).Results: A total of 345 DEGs were identified, and the proportions of gamma delta T cells, memory B cells, regulatory T cells (Tregs), and activated dendritic cells differed significantly between the control and pSS groups. The turquoise module indicated the highest correlation with pSS, and 252 key genes were identified. The PPI network of key genes showed that RPL9, RBX1, and RPL31 had a relatively higher degree. In addition, the key genes were mainly enriched in coronavirus disease-COVID-2019, hepatitis C, and influenza A. Fourteen feature genes were obtained using the support vector machine model, and two subtypes were identified. The genes in the two subtypes were mainly enriched in the JAK-STAT, p53, and toll-like receptor signaling pathways. The majority of the feature genes were upregulated in the pSS group, verified using the GEO datasets and RT-qPCR analysis.Conclusions: Memory B cells, gamma delta T cells, Tregs, activated dendritic cells, RPL9, RBX1, RPL31, and the feature genes possible play vital roles in the development of pSS.

Epithelial-immune cell interplay in primary Sjögren syndrome salivary gland pathogenesis.

In primary Sjögren syndrome (pSS), the function of the salivary glands is often considerably reduced. Multiple innate immune pathways are likely dysregulated in the salivary gland epithelium in pSS, including the nuclear factor-κB pathway, the inflammasome and interferon signalling. The ductal cells of the salivary gland in pSS are characteristically surrounded by a CD4+ T cell-rich and B cell-rich infiltrate, implying a degree of communication between epithelial cells and immune cells. B cell infiltrates within the ducts can initiate the development of lymphoepithelial lesions, including basal ductal cell hyperplasia. Vice versa, the epithelium provides chronic activation signals to the glandular B cell fraction. This continuous stimulation might ultimately drive the development of mucosa-associated lymphoid tissue lymphoma. This Review discusses changes in the cells of the salivary gland epithelium in pSS (including acinar, ductal and progenitor cells), and the proposed interplay of these cells with environmental stimuli and the immune system. Current therapeutic options are insufficient to address both lymphocytic infiltration and salivary gland dysfunction. Successful rescue of salivary gland function in pSS will probably demand a multimodal therapeutic approach and an appreciation of the complicity of the salivary gland epithelium in the development of pSS.

The Role of Interferons in the Pathogenesis of Sjögren's Syndrome and Future Therapeutic Perspectives.

There is a great deal of evidence pointing to interferons (IFNs) as being key cytokines in the pathogenesis of different systemic autoimmune diseases, including primary Sjögren’s syndrome (pSS). In this disease, a large number of studies have shown that an overexpression of type I IFN, the ‘so-called’ type I IFN signature, is present in peripheral blood mononuclear cells, and that this finding is associated with the development of systemic extra-glandular manifestations, and a substantial production of autoantibodies and inflammatory cytokines. In contrast, the absence or a milder expression of type I IFN signature and low level of inflammatory cytokines characterizes patients with a different clinical phenotype, where the disease is limited to glandular involvement and often marked by the presence of widespread pain and depression. The role of type II (IFNγ) in this subset of pSS patients, together with the potentially related activation of completely different immunological and metabolic pathways, are emerging issues. Expression of both types of IFNs has also been shown in target tissues, namely in minor salivary glands where a predominance of type II IFN signature appeared to have a certain association with the development of lymphoma. In view of the role played by IFN overexpression in the development and progression of pSS, inhibition or modulation of IFN signaling has been regarded as a potential target for the therapeutic approach. A number of therapeutic compounds with variable mechanisms of action have been tested or are under consideration for the treatment of patients with pSS.

The Role of the Microbiome in Sjogren's Syndrome.

The human microbiome is a living ecosystem existing within the host organism, determined by a balance between pathogenic microorganisms, symbionts, and commensals. The disturbance of microbiome composition-dysbiosis-often resulting in the excess of commensal numbers, may push the immune system towards activation of inflammatory and autoimmune processes. Changes in the microbiome of gut, eyes, and mouth may play a significant role in the development and course of autoimmune diseases, including primary Sjogren's syndrome. This autoimmune disease is associated with changes in the protective barrier of the epithelium, which is an important part of the antimicrobial defense. The development of pSS may be influenced by a mechanism of molecular mimicry between microbial antigens and self antigens leading to the initiation of anti-Ro60 antibody response. The knowledge of the influence of the state of microbiome on pSS may translate into the prophylaxis of the progression of dryness symptoms. The aim of this review is to present various aspects related to the human microbiome and Sjogren's syndrome.

A data-driven reversible framework for achieving Sustainable Smart product-service systems

Higher sustainability with extended product lifecycle is a tireless pursuit in companies’ product design/development endeavours. In this regard, two prevailing concepts, namely the smart circular system and smart product-service system (Smart PSS), have been introduced, respectively. However, most existing studies only focus on the sustainability of physical materials and components, without considering the cyber-physical resources as a whole, let alone an integrated strategy towards the so-called Sustainable Smart PSS. To fill the gap, this paper discusses the key features in Sustainable Smart PSS development from a broadened scope of cyber-physical resources management. A data-driven reversible framework is hereby proposed to sustainably exploit high-value and context-dependent information/knowledge in the development of Sustainable Smart PSS. A four-step context-aware process in the framework, including requirement elicitation, solution recommendation, solution evaluation, and knowledge evolvement, is further introduced to support the decision-making and optimization along the extended or circular lifecycle. An illustrative example is depicted in the sustainable development of a smart 3D printer, which validates the feasibility and advantages of the proposed framework. As an explorative study, it is hoped that this work provides useful insights for Smart PSS development with sustainability concerns in a cyber-physical environment.

Characterization of antiapoptotic microRNAs in primary Sjögren's syndrome.

During the development of primary Sjögren's syndrome (pSS), aberrant expression of autoantigen is a hallmark event. To explore the regulation of autoantigen tripartite motif containing 21 (Ro/SSA, TRIM21), microRNA profiling was performed in our previous study. In which, two TRIM21-targeting microRNAs were identified, namely miR-1207-5p and miR-4695-3p. To further pursue their roles in the development of pSS, assays were performed with cultured human submandibular gland (HSG) cells, and salivary gland tissues. Results showed that transfection of miR-1207-5p or miR-4695-3p mimics down-regulated not only the expression of TRIM21, but also the levels of pro-apoptotic genes B cell lymphoma 2 associated X (BAX), Caspase 9 (CASP-9) and Caspase 8 (CASP-8). This finally led to antiapoptotic phenotypes in HSG cells. Consistent with the antiapoptotic activity, transfection of microRNA inhibitors up-regulated the expression of TRIM21 and led to a pro-apoptotic phenotype. These therefore propose miR-1207-5p and miR-4695-3p as two antiapoptotic microRNAs functioning through apoptosis pathway. Supporting this speculation, assays performed with salivary gland tissues revealed down-regulation of miR-1207-5p and miR-4695-3p, as well as up-regulation of TRIM21 and pro-apoptotic CASP-8 gene in pSS samples. SIGNIFICANCE OF THE STUDY: For pSS patients, apoptosis of acinar and ductal epithelial cells has been proposed to be a potential mechanism that impairs the secretion of salivary glands. In our study, two autoantigen-targeting microRNAs were characterized as antiapoptotic microRNAs functioning through apoptosis pathway, which may be potential targets for the treatment of pSS.

Evolutionary design framework for Smart PSS: Service engineering approach

Digital technology is transforming industry, economy, and society. Under this digitalization trend, a new concept of product and service offerings, Smart PSS has been introduced. While the Smart PSS concept aiming at data-driven innovation attracts more attentions, there are two major challenges in designing Smart PSS. First, available data from digital technologies are actually limited by technical, financial, and social reasons. Second, the context of applying Smart PSS dynamically changes, which makes designed Smart PSS unfit to the target situation. To overcome these challenges, we propose an evolutionary design framework for Smart PSS. Our approach is based on the service engineering research, which has been contributing to the design and development of PSS. The proposed framework consists of three conceptual spaces and three cycles. The main features of the framework were two design cycles; in-system and ex-system design cycle. In-system design cycle is a process of creating and applying human knowledge for making the most use of data collected by digital technologies. Ex-system design cycle is to adapt to dynamic changes in contexts of the applied Smart PSS. We examine how the proposed framework works for designing a Smart PSS, with a case study about the digitalization of a restaurant business.

MiR-744-5p contributes to ocular inflammation in patients with primary Sjogrens Syndrome

In primary Sjögren’s syndrome (pSS) the exocrine glands become infiltrated with lymphocytes instigating severe damage to the salivary and lacrimal glands causing dry eyes and dry mouth. Previous investigations have suggested that dysregulated localized and systemic inflammation contributes to the development and pathogenesis of pSS. A miR microarray performed in primary human conjunctival epithelial cells (PECs) demonstrated significant differences in miR expression at the ocular surface between pSS patients and healthy controls. MicroRNA-744-5p (miR-744-5p) was identified as being of particular interest, as its top predicted target is Pellino3 (PELI3), a known negative regulator of inflammation. Validation studies confirmed that miR-744-5p expression is significantly increased in PECs from pSS patients, whilst PELI3 was significantly reduced. We validated the miR-744 binding site in the 3’ untranslated region (UTR) of PELI3 and demonstrated that increasing PELI3 levels with a miR-744-5p antagomir in an inflammatory environment resulted in reduced levels of IFN dependent chemokines Rantes (CCL5) and CXCL10. These results reveal a novel role for miR-744-5p in mediating ocular inflammation via Pellino3 expression in pSS patients and suggest that miR-744-5p may be a potential therapeutic target for the management of severe dry eye disease and ocular inflammation in pSS patients.

The role of Epstein-Barr virus infection in primary Sjögren's syndrome.

The purpose of this article is to draw attention to the role of Epstein-Barr virus (EBV) virus in the pathogenesis of the primary Sjögren's syndrome. The article introduces the problem of consequences of EBV acute infection, and its reactivation, in association with the immune response modulation by the virus and with an increased risk of developing systemic autoimmune diseases and EBV-associated cancers. The knowledge about the mechanisms by which the virus may stay for years in a latent phase, unrecognized by the host response immune cells is constantly expanding. There are several mechanisms and theories about EBV influence on the autoimmune process in Sjogren's syndrome (pSS), including the similarity (molecular mimicry) between viral EBNA-2 protein and Ro-60 antigen or EBER-1 and EBER-2 viral proteins and La antigen. The influence of EBV infection on the development and course of pSS has been proven. It has also been established that both EBV and pSS result in the increased risk of tumor (especially lymphoma) development. In the light of these findings, new ways to manage EBV infections are being sought. Optimal methods for assessing EBV infection status are being devised. Research also aims at finding therapies, which target EBV through the inhibition of the autoimmune process and of viral activity. The present article is an attempt to discuss the most important phenomena and elements linking EBV infection to the primary Sjögren's syndrome.

Overexpression of Smac is associated with the development of primary Sjogren's syndrome.

Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease characterized by keratoconjunctivitis sicca, xerostomia, and extraglandular abnormalities. The precise etiology remains unclear. Previous studies have revealed that the apoptosis played an important role in the pSS. Herein, we investigated the expression and effect of second mitochondria-derived activator of caspase (Smac) in patients with pSS and associated the expression with clinicopathological parameters. Smac expression was checked in labial salivary glands of surgical specimens from cases of pSS using immunohistochemistry, reverse transcription-quantitative PCR, and Western blot. The results of immunohistochemistry were analyzed for clinicopathological parameters. In addition, the content of Smac in cytoplasm and mitochondria were examined. The mRNA of Smac, the content of Smac in cytoplasm, the Smac protein in the pSS patients increased significantly compared with the healthy controls (p < 0.05). The content of Smac in mitochondria decreased significantly compared with the healthy controls (p < 0.05). The integral optical density of Smac protein levels were positively correlated with IgG (r = 0.7435, p < 0.05) and erythrocyte sedimentation rate (ESR) (r = 0.7925, p < 0.05). Smac plays an important role in the development of pSS.

Infections increase the risk of developing Sjögren's syndrome.

Environmental factors have been suggested in the pathogenesis of rheumatic diseases. We here investigated whether infections increase the risk of developing primary Sjögren's syndrome (pSS). Patients with pSS in Sweden (n=945) and matched controls from the general population (n=9048) were included, and data extracted from the National Patient Register to identify infections occurring before pSS diagnosis during a mean observational time of 16.0years. Data were analysed using conditional logistic regression models. Sensitivity analyses were performed by varying exposure definition and adjusting for previous health care consumption. A history of infection associated with an increased risk of pSS (OR 1.9, 95% CI 1.6-2.3). Infections were more prominently associated with the development of SSA/SSB autoantibody-positive pSS (OR 2.7, 95% CI 2.0-3.5). When stratifying the analysis by organ system infected, respiratory infections increased the risk of developing pSS, both in patients with (OR 2.9, 95% CI 1.8-4.7) and without autoantibodies (OR 2.1, 95% CI 1.1-3.8), whilst skin and urogenital infections only significantly associated with the development of autoantibody-positive pSS (OR 3.2, 95% CI 1.8-5.5 and OR 2.7, 95% CI 1.7-4.2). Furthermore, a dose-response relationship was observed for infections and a risk to develop pSS with Ro/SSA and La/SSB antibodies. Gastrointestinal infections were not significantly associated with a risk of pSS. Infections increase the risk of developing pSS, most prominently SSA/SSB autoantibody-positive disease, suggesting that microbial triggers of immunity may partake in the pathogenetic process of pSS.

Oral microbial flora of patients with Sicca syndrome.

Primary sicca syndrome (pSS) is a systemic autoimmune disease. However, its exact etiology and pathogenesis remain elusive. Various infectious factors have been identified to be closely associated with the occurrence and development of PSS. The present study aimed to assess the composition of the oral microbial flora of patients with pSS in China in order to provide guidance for treatment. The microbial flora of nine patients with pSS and five healthy controls from East China was evaluated in saliva samples using high-throughput sequencing. A high microbial diversity was detected in the pSS and control groups, with bacteroidetes, firmicutes and proteobacteria constituting the largest phyla in the two groups. Compared with the control group, bacteroidetes and actinobacteria were significantly more abundant in the pSS group, whereas proteobacteria were significantly less abundant. However, no significant differences in bacterial richness and diversity were observed between the two groups. According to a Kyoto Encyclopedia of Genes and Genomes linear discriminant analysis, genes regulating cell apoptosis and the immune and digestive systems were significantly upregulated in the pSS group compared with those in the control group. In conclusion, the present study provided basic data on the flora of the oral cavity in patients with pSS from East China and may serve as a reference for the treatment of this condition.

Increased frequency of CCR7+CD4+ T cells from patients with primary Sjögren's syndrome: An indicator of disease activity rather than of damage severity

Expression of CCR7 on T cells has been reported to be associated with the lymphocytic migration and infiltration, which is recognized as a vital part of the pathogenesis of Primary Sjögren's syndrome (pSS). Here, we compared the expression of CCR7 on CD4+T cells between pSS patients and control groups, including healthy donors (HD) and patients with systemic lupus erythematosus (SLE) and examined correlations with disease activity and damage severity, which were evaluated by EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) and Sjogren's Syndrome Disease Damage Index (SSDDI), respectively. Peripheral blood mononuclear Cells (PBMC) were obtained from patients and controls and expressions of CCR7 were evaluated by flow cytometry. CCR7 was selectively and frequently expressed on CD4+T cells, but less on CD8+ T cells of patients with pSS. In contrast, this phenomenon was neither seen in normal subjects nor in patients with SLE. The expression level of CCR7 in the peripheral blood CD4+ T cells is closely correlated with ESSDAI, but not SSDDI. Correspondently, the chemotactic index (CI) of CD4+T cells was higher than CD8+T cells in patients with pSS. Furthermore, the CI of CD4+T cells is also higher than that of other controls, which is correlated with ESSDAI. All the findings suggested that CCR7 might play an important role in the development of pSS by mediating the migration of CD4+cells. Thus, the expression of CCR7 in CD4+ T cells is probably a useful biomarker to evaluate and monitor disease activity. CCR7 can also potentially be a novel target for the therapy of pSS.

Detection and analysis on serum antibodies for five common pathogenic microbes in patients with Posner-Schlossmarm syndrome

Background Posner-Schlossman syndrome (PSS) is often recurrent and is a cause of blindness.The etiology of PSS remains to be elucidated.It is reported that there is a certain association between pathogenic microorganisms and PSS in rather small samples. Objective This study was to analyze the related serum antibody levels of cytomegalovirus (CMV), herpes simplex virus (HSV), rubella virus (RV), helicobacter pylori (HP) and anti-streptolysin O (ASO) and provide a clue for the study on pathogenesis and therapy of PSS. Methods A prospective cases-controlled study was carried out in Shenzhen Eye Hospital from December, 2014 to December, 2016 under the approval of Ethic Committee of this hospital and informed consent of each subject prior to initial of any medical examination.Peripheral blood samples were collected from 82 PSS patients as the PSS group and 100 age-and gender-matched healthy blood donors as the normal control group.The positive rates of serum CMV IgG, CMV IgM, HSV IgG, HSV IgM, RV IgG, RV IgM, HP IgG and HP IgM in the subjects were detected by indirect ELISA, and the positive rate of serum ASO antibody was determined by immuno-scatter turbidmetry. Results The positive rates of serum CMV-IgG, CMV-IgM, HP-IgG, HP-IgM and ASO antibody were 22.0%, 17.1%, 22.0%, 17.1% and 17.1% in the PSS group, which were significantly higher than 5.0%, 0.0%, 10.0%, 2.0% and 7.0% in the normal control group (χ2=11.726, 18.496, 4.943, 12.766, 4.479, all at P 0.05). Conclusions CMV, HP and hemolytic streptococcal infection may participate in the occurrence and development of PSS. Key words: Posner-Schlossman syndrome; Etiology; Cytomegalovirus; Herpes simplex virus; Rubella virus; Helicobacter pylori; Anti-streptolysin O; Antibody

Cytochrome c is important in apoptosis of labial glands in primary Sjogren's syndrome.

The present study aimed to investigate the expression and effect of cytochrome c (Cytc) in patients with primary Sjogren's syndrome (pSS). In total, 35newly diagnosed pSS patients and 35 healthy subjects were enrolled in the present study. The mRNA expression levels of Cytc were detected using reverse transcription‑polymerase chain reaction and RT‑quantitative PCR. The expression of the Cytc protein in labial salivary glands was detected by immunohistochemistry and was associated with the integral optical density (IOD) of clinical and laboratory variables. In addition, the content of Cytc in the cytoplasm and mitochondria were examined. The mRNA and protein expression levels of Cytc, and the content of Cytc in the cytoplasm of the pSS patients was increased significantly compared with the healthy controls (P<0.05). The content of Cytc in the mitochondria was significantly decreased compared with the healthy controls (P<0.05). The IOD of Cytc protein levels was positively correlated with immunoglobinG (r=0.8142, P<0.05) and erythrocyte sedimentation rate (r=0.7512, P<0.05). Cytc was upregulated in the pSS patients, indicating the potential role of Cytc in the pathogenesis and development of pSS. Further studies may facilitate the development of targeting this molecular pathway for the treatment of pSS.

Investigation of three potential autoantibodies in Sjogren's syndrome and associated MALT lymphoma

Primary Sjögren's syndrome (pSS) is a chronic autoimmune disease which might progress to mucosal-associated lymphoid tissue lymphoma (pSS/MALT). Diagnosis of pSS requires an invasive tissue biopsy and a delay in diagnosis of pSS has been frequently reported. In this study, four proteins including cofilin-1, alpha-enolase, annexin A2 and Rho GDP-dissociation inhibitor 2 (RGI2) were found to be over-expressed in pSS and pSS/MALT by 2D gel electrophoresis/mass spectrometry, and the finding was verified by the microarray analysis and western blotting results. We then developed enzyme-linked immunosorbent assays for autoantibodies including anti-cofilin-1, anti-alpha-enolase and anti-RGI2 with good quantitative ability. The expression levels of salivary anti-cofilin-1, anti-alpha-enolase and anti-RGI2 were found to be the highest in pSS/MALT patients and lowest in healthy controls. The combination of these three antiantibodies yielded an “area under the curve” (AUC) value of 0.94 with an 86% sensitivity and 93% specificity in distinguishing patients with pSS from healthy controls, an AUC value of 0.99 with a 95% sensitivity and 94% specificity in distinguishing patients with pSS/MALT from healthy controls and an AUC value of 0.86 with a 75% sensitivity and 94% specificity in distinguishing pSS/MALT patients from pSS patients. Collectively, we have successfully identified a panel of potential autoantigens that are progressively up-regulated during the development of pSS and its progression to MALT lymphoma. The autoantibody biomarkers may be used to help diagnose pSS and predict its progression to MALT lymphoma.

PSS in Healthcare: An Under-Explored Field

This paper reports the preliminary results of a research aiming at delineating the state-of-the-art literature concerned with the application of PSS in the healthcare industry. Following a structured literature review process, 23 studies are identified as the most relevant for the review. These studies are classified along the following dimensions: (i) research methods; (ii) motivations driving the development of PSS in healthcare; and (iii) focus and stakeholders of PSS applications. This paper reveals that despite the healthcare industry has always been conceived as an area where PSS can have a huge potential, studies on this topic is still very scant.

Roles of Epstein-Barr virus in the pathogenesis of primary Sjögren′s syndrome

Primary Sjogren′s syndrome (pSS) is a kind of chronic autoimmune disease affecting many organs of the body. The pathogenesis of pSS is still debated. Epstein-Barr virus(EBV), also called human herpesvirus-4, belongs to the herpesviridae family. Researchers have found that EBV is associated with pSS. With the deepening of researches, more evidences and opinions about the participation of EBV in the pathogenesis of pSS have emerged. EBV can cause the development of pSS in multiple ways. In this review, we summarize the roles of EBV in the pathogenesis of pSS. Key words: Sjogren′s syndrome; Epstein-Barr virus; Interferon; Lymphoma