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Integrated Analyses of Gene Expression Profiles Digs out Common Markers for Rheumatic Diseases.

ABSTRACT: Rheumatic diseases have some common symptoms. Extensive gene expression studies, accumulated thus far, have successfully identified signature molecules for each rheumatic disease, individually. However, whether there exist shared factors across rheumatic diseases has yet to be tested.We collected and utilized 6 public microarray datasets covering 4 types of representative rheumatic diseases including rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, and osteoarthritis. Then we detected overlaps of differentially expressed genes across datasets and performed a meta-analysis aiming at identifying common differentially expressed genes that discriminate between pathological cases and normal controls. To further gain insights into the functions of the identified common differentially expressed genes, we conducted gene ontology enrichment analysis and protein-protein interaction analysis.We identified a total of eight differentially expressed genes (TNFSF10, CX3CR1, LY96, TLR5, TXN, TIA1, PRKCH, PRF1), each associated with at least 3 of the 4 studied rheumatic diseases. Meta-analysis warranted the significance of the eight genes and highlighted the general significance of four genes (CX3CR1, LY96, TLR5, and PRF1). Protein-protein interaction and gene ontology enrichment analyses indicated that the eight genes interact with each other to exert functions related to immune response and immune regulation.The findings support that there exist common factors underlying rheumatic diseases. For rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis and osteoarthritis diseases, those common factors include TNFSF10, CX3CR1, LY96, TLR5, TXN, TIA1, PRKCH, and PRF1. In-depth studies on these common factors may provide keys to understanding the pathogenesis and developing intervention strategies for rheumatic diseases.

SUBMITTER: Wang L

PROVIDER: S-EPMC4564267 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Integrated Analyses of Gene Expression Profiles Digs out Common Markers for Rheumatic Diseases.

Wang Lan L Wu Long-Fei LF Lu Xin X Mo Xing-Bo XB Tang Zai-Xiang ZX Lei Shu-Feng SF Deng Fei-Yan FY

PloS one 20150909 9

<h4>Objective</h4>Rheumatic diseases have some common symptoms. Extensive gene expression studies, accumulated thus far, have successfully identified signature molecules for each rheumatic disease, individually. However, whether there exist shared factors across rheumatic diseases has yet to be tested.<h4>Methods</h4>We collected and utilized 6 public microarray datasets covering 4 types of representative rheumatic diseases including rheumatoid arthritis, systemic lupus erythematosus, ankylosing ...[more]

PMID: 26352601

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Project description:BackgroundActivated T lymphocytes play an important role in the pathogenesis of rheumatic diseases (RD). Mesenchymal stem cells (MSCs) possess immunoregulatory activities but such functions of MSCs from bone marrow of systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and ankylosing spondylitis (AS) patients are impaired. Adipose tissue-derived MSCs (ASCs) are an optional pool of therapeutically useful MSCs, but biology of these cells in RD is poorly known. This study aimed at investigating the effect of ASCs from RD patients and healthy donors (HD) on the expression of the key T-cell activation markers.MethodsASCs were isolated from subcutaneous abdominal fat from SLE (n = 16), SSc (n = 18), and AS (n = 16) patients, while five human ASCs lines from HD were used as a control. Untreated and cytokine (tumor necrosis factor α + interferon γ)-treated ASCs were co-cultured with allogenic, mitogen (phytohemagglutinin)-stimulated peripheral blood mononuclear cells (PBMCs) or purified anti-CD3/CD28-activated CD4+ T lymphocytes. Contacting and noncontacting ASCs-PBMCs co-cultures were performed. RD/ASCs were analyzed in co-cultures with both allogeneic and autologous PBMCs. Flow cytometry analysis was used to evaluate expression of CD25, HLA-DR, and CD69 molecules on CD4+ and CD8+ cells.ResultsIn co-cultures with allogeneic, activated CD4+ T cells and PBMCs, HD/ASCs and RD/ASCs downregulated CD25 and HLA-DR, while upregulated CD69 molecules expression on both CD4+ and CD8+ cells with comparable potency. This modulatory effect was similar in contacting and noncontacting co-cultures. RD/ASCs exerted weaker inhibitory effect on CD25 expression on autologous than allogeneic CD4+ and CD8+ T cells.ConclusionRD/ASCs retain normal capability to regulate expression of activation markers on allogeneic T cells. Both HD/ASCs and RD/ASCs exert this effect independently of their activation status, mostly through the indirect pathway and soluble factors. However, autologous CD4+ and CD8+ T cells are partially resistant to RD/ASCs inhibition of CD25 expression, suggesting weaker control of T-cell activation in vivo.

Project description:OBJECTIVE:To describe a one-stop, integrated rheumatology service and assess patient satisfaction. METHODS:A descriptive report and patient satisfaction survey of a rheumatology clinic model first developed in 1996 to enhance the patient "journey" through rheumatology services. A patient-satisfaction survey over a 3-week period assessed several aspects of care including quality of services, consultations, and patient education. RESULTS:All referrals are screened by a rheumatologist to pre-schedule laboratory/radiology/other tests for the visit. Upon arrival to the clinic, patients check-in at an electronic desk, and then complete the electronic GoTreatIT monitoring system which assesses patient-reported outcomes. The patient is reviewed by a doctor in a 30- to 60-min consultation, and then by a nurse (for diagnosis/treatment education, vaccinations). An ultrasound machine and capillaroscopy are available for use in the clinic. Patients can be scheduled on the same day to see a nutritionist, physiotherapist, or other heath professionals as necessary. An "early-rheumatoid arthritis treatment path" is available to ensure early, intensive treatment. A patient satisfaction survey revealed high rating of the overall service (90.6/100). None of the patients felt that they lacked education on their disease or medication. Only 6% of the respondents gave negative feedback, reasons including feeling overwhelmed with information or not being given a cause for their symptoms. The multi-disciplinary approach was highly valued and only 3% would rather see a doctor and nurse on separate days. CONCLUSION:The specific clinic model provides an ideal setting for a one-stop service, avoiding unnecessary visits, collecting patient data, and enhancing the patient experience and journey through the system. Where possible, the specific clinic model could be used or adapted to build similar models in other rheumatology departments. The clinic model could also form the basis for services in other specialties dealing with chronic conditions.

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Integrated Analyses of Gene Expression Profiles Digs out Common Markers for Rheumatic Diseases.

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Integrated Analyses of Gene Expression Profiles Digs out Common Markers for Rheumatic Diseases.

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