Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 28266627 | CCN1 promotes IL-1β production in keratinocytes by activating p38 MAPK signaling in psori | 2017 Mar 7 | CCN1, an extracellular protein also known as cysteine-rich protein 61 (Cyr61), is a novel pro-inflammatory factor involved in the pathogenesis of rheumatoid arthritis. As an inflammatory disease, psoriasis is characterized by keratinocyte activation-induced epidermal hyperplasia and cytokine-mediated inflammation. We demonstrated in our previous study that CCN1 promoted keratinocyte activation in psoriasis. However, the role of CCN1 in regulating inflammation in psoriasis is still unknown. Here, we showed that CCN1 increased inflammatory cytokine IL-1β production in keratinocytes. Furthermore, endogenous ATP and caspase-1 were required for mature IL-1β production stimulated by CCN1 in keratinocytes. After binding to the receptor of integrin α6β1, CCN1 activated the downstream p38 MAPK signaling pathway, thus inducing the expression of IL-1β. In addition, we inhibited CCN1 function in mouse models of psoriasis, and decreased IL-1β production was observed in vivo. Overall, we showed that CCN1 increased IL-1β production via p38 MAPK signaling, indicating a role for CCN1 protein in regulating inflammation in psoriasis. | |
| 28261211 | Targeting the Monocyte-Macrophage Lineage in Solid Organ Transplantation. | 2017 | There is an unmet clinical need for immunotherapeutic strategies that specifically target the active immune cells participating in the process of rejection after solid organ transplantation. The monocyte-macrophage cell lineage is increasingly recognized as a major player in acute and chronic allograft immunopathology. The dominant presence of cells of this lineage in rejecting allograft tissue is associated with worse graft function and survival. Monocytes and macrophages contribute to alloimmunity via diverse pathways: antigen processing and presentation, costimulation, pro-inflammatory cytokine production, and tissue repair. Cross talk with other recipient immune competent cells and donor endothelial cells leads to amplification of inflammation and a cytolytic response in the graft. Surprisingly, little is known about therapeutic manipulation of the function of cells of the monocyte-macrophage lineage in transplantation by immunosuppressive agents. Although not primarily designed to target monocyte-macrophage lineage cells, multiple categories of currently prescribed immunosuppressive drugs, such as mycophenolate mofetil, mammalian target of rapamycin inhibitors, and calcineurin inhibitors, do have limited inhibitory effects. These effects include diminishing the degree of cytokine production, thereby blocking costimulation and inhibiting the migration of monocytes to the site of rejection. Outside the field of transplantation, some clinical studies have shown that the monoclonal antibodies canakinumab, tocilizumab, and infliximab are effective in inhibiting monocyte functions. Indirect effects have also been shown for simvastatin, a lipid lowering drug, and bromodomain and extra-terminal motif inhibitors that reduce the cytokine production by monocytes-macrophages in patients with diabetes mellitus and rheumatoid arthritis. To date, detailed knowledge concerning the origin, the developmental requirements, and functions of diverse specialized monocyte-macrophage subsets justifies research for therapeutic manipulation. Here, we will discuss the effects of currently prescribed immunosuppressive drugs on monocyte/macrophage features and the future challenges. | |
| 28246653 | Diabetes, Obesity, and Other Medical Diseases - Is Surgery the Answer? | 2017 Mar 1 | For many physicians, the concept of surgery as the best treatment for a medical disease such as diabetes, cardiovascular problems, hyperlipidemia, sleep apnea, hepatosteatosis, GERD, osteoarthritis, psoriasis, rheumatoid arthritis, or infertility, still sounds wrong and just a ploy by surgeons to increase their business. Since 2011, however, several non-surgical societies have recommended Weight Loss Surgery - The International Diabetes Federation, The American Diabetes Association, American Heart Association, and Obesity Society in 2015 for patients with body mass index (BMI) greater than 35 and diabetes, and to decrease cardiovascular risk factors.1 The concept is to treat the common underlying problem, which is obesity, with the most effective method for immediate and long-term weight loss, which is surgery. The term "metabolic" surgery was therefore coined to accurately describe the effects of weight loss (bariatric) surgery. Our specialty society named itself the American Society for Metabolic and Bariatric Surgery (ASMBS). [Full article available at http://rimed.org/rimedicaljournal-2017-03.asp]. | |
| 28160754 | The role of IL17B-IL17RB signaling pathway in breast cancer. | 2017 Apr | Breast cancer is the most important cause of death in women globally. Though, improved survival is due to the developments in the screening techniques, initial diagnosis, and advances in treatments. Numerous factors contributed in the progression of breast cancer, such as inflammation. The most significant factor involved in the inflammatory process, is T helper 17 (Th17) cells. Th17 cells have an exceptional role in many of inflammatory diseases like psoriasis, rheumatoid arthritis, and breast cancer through production of proinflammatory cytokine (IL17). As the collected indication recommends a possible relevance between chronic inflammation and cancer tumorigenesis, it appears that this cytokine can stimulate the tumorigenesis of breast tumor cells. The IL17 family consist of 6 protein members, among them IL17B and its receptor, and IL17RB signaling pathway plays a key role in development and progression of breast cancer, and targeting this signaling pathway or its specific downstream mediators by a chemotherapy drug and small interfering RNA interference is a potentially novel therapeutic pathway for inhibition of this disease. This comprehensive review details the recognition of activity, signaling, and the roles of IL17B-IL17RB in breast cancer have caused to determination of new therapeutic mechanisms with the purpose of introduction this system and the regulation of its signaling pathway. | |
| 28001129 | A multispectral microscope for in vivo oximetry of rat dorsal spinal cord vasculature. | 2017 Feb | Quantification of blood oxygen saturation (SO(2)) in vivo is essential for understanding the pathogenesis of diseases in which hypoxia is thought to play a role, including inflammatory disorders such as multiple sclerosis (MS) and rheumatoid arthritis (RA). We describe a low-cost multispectral microscope and oximetry technique for calibration-free absolute oximetry of surgically exposed blood vessels in vivo. We imaged the vasculature of the dorsal spinal cord in healthy rats, and varied inspired oxygen (FiO(2)) in order to evaluate the sensitivity of the imaging system to changes in SO(2). The venous SO(2) was calculated as 67.8  ±  10.4% (average  ±  standard deviation), increasing to 83.1  ±  11.6% under hyperoxic conditions (100% FiO(2)) and returning to 67.4  ±  10.9% for a second normoxic period; the venous SO(2) was 50.9  ±  15.5% and 29.2  ±  24.6% during subsequent hypoxic states (18% and 15% FiO(2) respectively). We discuss the design and performance of our multispectral imaging system, and the future scope for extending this oximetry technique to quantification of hypoxia in inflamed tissue. | |
| 27882473 | Foxp3, Regulatory T Cell, and Autoimmune Diseases. | 2017 Feb | Regulatory T cells (Tregs) represent a cell type that promotes immune tolerance to autologous components and maintains immune system homeostasis. The abnormal function of Tregs is relevant to the pathogenesis of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and other autoimmune diseases. Therefore, therapeutic modulation of Tregs could be a potent means of treating autoimmune diseases. Human Tregs are diverse, however, and not all of them have immunosuppressive effects. Forkhead box P3 (Foxp3), a pivotal transcription factor of Tregs that is crucial in maintaining Treg immunosuppressive function, can be expressed heterogeneously or unstably across Treg subpopulations. Insights into modulating Treg differentiation on the level of DNA transcription or protein modification may improve the success of Treg modifying immunotherapies. In this review, we will summarize three main prospects: the regulatory mechanism of Foxp3, the influence on Foxp3 and Tregs in autoimmune diseases, then finally, how Tregs can be used to treat autoimmune diseases. | |
| 27881864 | Mass spectrometry imaging: a novel technology in rheumatology. | 2017 Jan | Mass spectrometry imaging (MSI) is used to determine the relative abundance and spatial distribution of biomolecules such as peptides, proteins, lipids and other organic compounds in tissue sections by their molecular masses. This technique provides a sensitive and label-free approach for high-resolution imaging, and is currently used in an increasing number of biomedical applications such as biomarker discovery, tissue classification and drug monitoring. Owing to technological advances in the past 5 years in diverse MSI strategies, this technology is expected to become a standard tool in clinical practice and provides information complementary to that obtained using existing methods. Given that MSI is able to extract mass-spectral signatures from pathological tissue samples, this technique provides a novel platform to study joint-related tissues affected by rheumatic diseases. In rheumatology, MSI has been performed on articular cartilage, synovium and bone to increase the understanding of articular destruction and to characterize diagnostic and prognostic biomarkers for osteoarthritis, rheumatoid arthritis and osteoporosis. In this Review, we provide an overview of MSI technology and of the studies in which joint tissues have been analysed by use of this methodology. This approach might increase knowledge of rheumatic pathologies and ultimately prompt the development of targeted strategies for their management. | |
| 27629281 | RORγ antagonists and inverse agonists: a patent review. | 2017 Jan | The transcription factor RORγ plays a critical role in the expression of pro-inflammatory cytokine interleukin IL-17 and is therefore an attractive target for the treatment of inflammatory diseases. Interest in this molecular target has been heightened by the advancement of orally and topically administered RORγ modulators into clinical trials. Areas covered: The present review seeks to summarize published patent applications from assignee companies that have disclosed Investigational New Drug (IND) filings for small molecule RORγ/RORγt antagonists and inverse agonists. Expert opinion: The field of RORγ research is extremely competitive, with the majority of companies targeting psoriasis as the primary disease indication. Vitae Pharmaceuticals is currently the most advanced, with a potential first-in-class oral RORγ-modulator for the treatment of psoriasis. Future efforts will likely expand into potential applications of RORγ-modulators in the lesser explored immune-related areas of rheumatoid arthritis, type 1 diabetes, lupus, and irritable bowel disorder, as well as cancer immunotherapy and castration-resistant prostate cancer. | |
| 27580425 | Differences in expression of Wnt antagonist Dkk1 in healthy versus pathological bone sampl | 2017 Jan | Wnt/β-catenin signalling components was shown to affect bone cells function including chondrocytes.Secreted Dkk1, a potent osteogenesis inhibiting factor mediates bone loss in diseased bones by suppressing the biological actions of Wnt proteins. In addition, increased Dkk1 signalling inhibits chondrogenesis in new bone formation. Recent findings also show there exists a cross-talk between the chondrocytes and the cells of the osteoblast lineage, which are the most affected cell types in muskuloskeletal disorders. This study investigated whether spatial expression of Dkk1 is confined to only osteoblasts, osteocytes or chondrocytes. The second objective was to detect a difference in the Dkk1 expression pattern in healthy subjects when compared to pathological state. To elucidate the cell specificity of Dickkopf-1 (Dkk1) in healthy bones, samples from female Sprague-Dawley rats were tested against two different antibodies with the two most widely accepted visualization system (ABC and Envision). The findings show Dkk1 specificity predominantly for osteoblasts, chondrocytes and osteocytes depending upon the antibody used. In addition, Dkk1 expression was evaluated in different cells of human osteoarthritis (OA) and rheumatoid arthritis (OA) patients. Its overexpression in pathologic state also suggests the role of Dkk1 in bone formation. This is scientifically and clinically important in studying the effect of Dkk1 in bone healing and in designing treatments for patients with compromised bone status. Taking into consideration the paradigm that cartilage and subchondral bone behave as an interconnected functional unit, normalization of cell behaviour in one compartment may have benefits in both tissues. | |
| 27377297 | Anti-phospholipid Antibodies and Smoking: An Overview. | 2017 Aug | Antiphospholipid syndrome is characterized by the presence of antiphospholipid antibodies, specifically lupus anticoagulant, anticardiolipin antibodies, and anti-β2 glycoprotein-I antibodies. Antiphospholipid syndrome can occur on its own or in association with other autoimmune diseases, most commonly systemic lupus erythematosus (SLE). A connection between cigarette smoking and anti-phospholipid antibodies (aPL) was first reported in the late1980s. Systemic lupus erythematosus patients with aPL are more likely to be smokers than those without aPL. These patients have a particularly high frequency of vascular events. Recently, a potential link between periodontitis, tobacco, and aPL has been proposed. Research has also suggested that periodontitis and Porphyromonas gingivalis infection are associated with citrullination through the action of peptidylarginine deiminase. A strong correlation between smoking and the presence of citrillunated autoantibodies, which are characteristic of rheumatoid arthritis, has also been observed. While many studies have investigated possible links between infection and aPL in patients with autoimmune diseases, the association of smoking with aPL has not been systematically examined. The fact that both aPL and tobacco are risk factors for thrombosis has complicated efforts to evaluate these factors separately. Also, there has been great variability in measurement techniques, and laboratories lack routine methods for differentiating transient and persistent aPL; both of these factors can make interpretation of autoantibody results quite challenging. This review summarizes the clinical evidence supporting a posited link between aPL and smoking, both in patients with a systemic autoimmune disease and in patients with other medical conditions. | |
| 29243407 | Rheumatic diseases are associated with a higher risk of dementia: A nation-wide, populatio | 2018 Feb | AIM: Previous research demonstrated the possible relevance of dementia and rheumatic diseases. This population-based study aims to investigate the association of rheumatic diseases and dementia. METHODS: The data of this case-control study was extracted from the Taiwan National Health Insurance Research Database. Diagnosis of dementia and rheumatic diseases mentioned in this study were retrieved by the International Classification of Diseases-9 code. We recruited cases (n = 10 180) with dementia and controls (n = 61 080) during 2000-2010, by matching on age, gender and index date with a match ratio 1 : 6. The Chi-square test was used to calculate the baseline characteristics of the cases and controls for categorical variables such as age and gender. Simple conditional and multivariable conditional logistic regression models were used to estimate crude and adjusted odds ratios. RESULTS: Statistical significance was observed in Sjögren's syndrome (SS), systemic lupus erythematosus (SLE), and osteoarthritis (OA) among females (P < 0.05 for SS and SLE; P < 0.01 for OA), and in SS, psoriatic arthritis (PsA) and OA among males (P < 0.01 for SS; P < 0.05 for PsA and OA). Further, we also demonstrated a significant difference in SLE and OA among the younger group (age = 40-64) (P < 0.01 for SLE and OA), and in SS and OA among the older group (age ≧ 65) (P < 0.01 for SS and OA). CONCLUSION: In this population-based case-control study, we found that patients with rheumatoid arthritis, SS, SLE, PsA and OA are significantly associated with a higher risk of dementia than those without rheumatic diseases. We hypothesized that inflammation and medications are two possible mechanisms. | |
| 29037536 | Open reduction and internal fixation for nonunion of extra-articular distal humeral fractu | 2018 Jan | HYPOTHESIS: The study purpose was to report the clinical and radiologic outcomes of osteosynthesis by open reduction and internal fixation for nonunion of extra-articular distal humeral fractures in patients aged 70 years or older. MATERIALS AND METHODS: This retrospective study included 28 patients who received osteosynthesis treatment between March 2010 and December 2015. Primary conservative treatment had failed in all patients. All surgical procedures were performed via the posterior approach without olecranon osteotomy and with the use of double-locking plates for each column. RESULTS: The mean patient age was 72 years, and surgical procedures were performed a mean of 7.6 months after injury. Preoperatively, extension-flexion was 32° to 101° and forearm pronation-supination was 74° to 47°. The mean visual analog scale score was 4; the mean Mayo Elbow Performance Score was 50; and the mean Disabilities of the Arm, Shoulder and Hand score was 58. All cases showed proper union after a mean of 5.2 months. At the final follow-up examination, the extension-flexion and rotation arcs had improved significantly (to 20° to 124° and to 80° to 66°, respectively; both P < .001), and all clinical scores were satisfactory (visual analog scale score, 1; Mayo Elbow Performance Score, 65; and Disabilities of the Arm, Shoulder and Hand score, 24; all P < .001). Ulnar nerve transposition was performed in 7 patients, and no distinct ulnar nerve symptom was observed in any patient at the final follow-up examination. CONCLUSIONS: We consider osteosynthesis by open reduction and internal fixation as a recommended option for extra-articular distal humeral fractures in elderly patients aged 70 years or older in whom conservative treatment has failed. | |
| 29045077 | Subjective Complaints as the Main Reason for Biosimilar Discontinuation After Open-Label T | 2018 Jan | OBJECTIVE: To evaluate drug survival, effectiveness, pharmacokinetics, immunogenicity, and safety in daily practice after transitioning treatment from original reference infliximab (Remicade [REM]) to a biosimilar infliximab (CT-P13 [Remsima; Inflectra]) in patients with rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis. METHODS: Of the initial 222 REM-treated patients, 192 agreed to transition to CT-P13 and were included in this multicenter prospective cohort study. Changes in the Disease Activity Score in 28 joints using the C-reactive protein level (DAS28-CRP) and the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and changes in the CRP levels, infliximab trough levels, and anti-infliximab antibody levels were assessed after 6 months, and adverse events (AEs) were documented. Drug survival and prognostic factors were analyzed using Kaplan-Meier and Cox regression analyses. RESULTS: During 6 months follow-up, 24% of the patients (n = 47) discontinued CT-P13. Thirty-seven patients restarted REM, 7 switched to another biologic drug, and 3 continued without a biologic drug. The DAS28-CRP remained stable from baseline to month 6, with a mean ± SD score of 2.2 ± 0.9 at baseline to 2.2 ± 0.8 at 6 months (difference of 0.0 [95% confidence interval (95% CI) -0.1, 0.2]). The BASDAI increased from a mean ± SD of 3.8 ± 2.0 at baseline to 4.3 ± 2.1 at 6 months (difference of +0.5 [95% CI 0.1, 0.9]). The CRP levels, infliximab trough levels, and anti-infliximab antibody levels did not change. Just prior to CT-P13 discontinuation, the DAS28-CRP components tender joint count and patient's global assessment of disease activity, as well as the BASDAI were increased compared to baseline. The most frequently reported AEs were arthralgia, fatigue, pruritus, and myalgia. A shorter REM infusion interval (hazard ratio: 0.77 [95% CI 0.62, 0.95]) at baseline was predictive of discontinuing CT-P13. CONCLUSION: In our cohort, one-fourth of patients discontinued CT-P13 during 6 months of follow-up, mainly due to an increase in the subjective features of the tender joint count and the patient's global assessment of disease activity and/or subjective AEs, possibly explained by nocebo effects and/or incorrect causal attribution effects. | |
| 28360983 | Association Between Serum 25-Hydroxyvitamin D Levels and Dry Eye in Korean Adults: A Study | 2017 Mar | BACKGROUND: Dry eye is a common disease. Many patients continue to experience residual symptoms despite optimal treatment. Thus, new treatment options are required. The purpose of this study was to evaluate the association between serum 25-hydroxyvitamin D [25(OH)D] levels and dry eye. METHODS: This study was performed using data from the fifth Korean National Health and Nutrition Examination Survey, which is a cross-sectional study of the Korean population that was conducted from 2010 to 2011. We included adults aged >19 years who underwent ophthalmologic interviews and examinations. We excluded subjects who had comorbid conditions (rheumatoid arthritis, thyroid disease, chronic kidney disease, or depression) that are associated with dry eye. The subjects were divided into normal and dry eye groups. The dry eye group consisted of those who had clinically diagnosed dry eye syndrome or symptoms. Multiple logistic regression analysis was conducted to determine the association between serum 25(OH)D levels and dry eye. RESULTS: In the univariate model, the 25(OH)D levels were lower in the dry eye group than in the normal group (P=0.01). A significant association was found between severe vitamin D deficiency (<10 ng/mL) and dry eye (P=0.04). However, after multivariate adjustment, the statistical significance of the association disappeared (P-values= 0.49, vitamin D insufficiency; P=0.33, vitamin D deficiency; P=0.18, severe vitamin D deficiency). CONCLUSION: Severe vitamin D deficiency was associated with dry eye in an unadjusted model, but the association was not statistically significant after adjustment. | |
| 28916716 | Deregulation of microRNA expression in purified T and B lymphocytes from patients with pri | 2018 Jan | OBJECTIVE: MicroRNAs (miRNAs) play an important role in the pathogenesis of autoimmune diseases such as primary Sjögren's syndrome (pSS). This study is the first to investigate miRNA expression patterns in purified T and B lymphocytes from patients with pSS using a high-throughput quantitative PCR (qPCR) approach. METHODS: Two independent cohorts of both patients with pSS and controls, one for discovery and one for replication, were included in this study. CD4+ T cells and CD19+ B cells were isolated from peripheral blood mononuclear cells by magnetic microbeads and expression of miRNAs was profiled using the Exiqon Human miRNome panel I analysing 372 miRNAs. A selection of differentially expressed miRNAs was replicated in the second cohort using specific qPCR assays. RESULTS: A major difference in miRNA expression patterns was observed between the lymphocyte populations from patients with pSS and controls. In CD4 T lymphocytes, hsa-let-7d-3p, hsa-miR-155-5 p, hsa-miR-222-3 p, hsa-miR-30c-5p, hsa-miR-146a-5p, hsa-miR-378a-3p and hsa-miR-28-5 p were significantly differentially expressed in both the discovery and the replication cohort. In B lymphocytes, hsa-miR-378a-3p, hsa-miR-222-3 p, hsa-miR-26a-5p, hsa-miR-30b-5p and hsa-miR-19b-3p were significantly differentially expressed. Potential target mRNAs were enriched in disease relevant pathways. Expression of B-cell activating factor (BAFF) mRNA was inversely correlated with the expression of hsa-miR-30b-5p in B lymphocytes from patients with pSS and functional experiments showed increased expression of BAFF after inhibiting hsa-miR-30b-5p. CONCLUSIONS: This study demonstrates major miRNAs deregulation in T and B cells from patients with pSS in two independent cohorts, which might target genes known to be involved in the pathogenesis of pSS. | |
| 28665757 | Functional Epitopes for Anti-Aquaporin 5 Antibodies in Sjögren Syndrome. | 2017 Nov | We recently reported the presence of anti-aquaporin 5 (AQP5) immunoglobulin G (IgG) in patients with primary Sjögren syndrome (SS) with a sensitivity of 0.73 and a specificity of 0.68. The aim of this study was to identify functional epitopes for the anti-AQP5 autoantibodies detected in control subjects and patients with SS. Recognition of epitopes by anti-AQP5 autoantibodies in sera ( n = 13 for control and n = 24 for SS) or purified IgG ( n = 1 for control and n = 3 for SS) was evaluated by indirect immunofluorescence (IIF) assay performed in the presence or absence of peptides corresponding to the second transmembrane helix and extracellular loops A, C, and E of AQP5. Functional epitopes were determined by measuring the effects of purified IgG and neutralizing peptides on transepithelial osmotic permeability (P(f)(T)) of MDCK cells expressing AQP5. In the IIF assay, 89% of SS samples were inhibited by at least 1 peptide, while only half of control samples were inhibited by any peptide. Overall, SS samples were inhibited by peptides corresponding to extracellular loops A, C, and E by 40% to 50%, whereas control samples were inhibited only by peptides corresponding to loop E by <20%. A cyclized peptide (E1) mimicking loop E was most frequently recognized and best differentiated between the SS and control samples. Incubation of MDCK-AQP5 cells with SS but not with control IgG, significantly decreased P(f)(T), which was reversed by neutralization of IgG binding to any of the extracellular loops. In conclusion, the anti-AQP5 autoantibodies detected in control and SS groups showed differences in fine specificity to the functional epitopes of AQP5. The prevalent recognition of functional epitopes by anti-AQP5 autoantibodies from SS patients suggests that anti-AQP5 autoantibodies act as mediators of glandular hypofunction and are a potential therapeutic target in SS. | |
| 29033144 | Impaired anti-inflammatory activity of PPARγ in the salivary epithelia of Sjögren's synd | 2018 Jan | Sjögren's syndrome (SS) patients manifest inflammation in the salivary glands (SG) and evidence of persistent intrinsic activation of ductal SG epithelial cells (SGEC), demonstrable in non-neoplastic SGEC lines derived from patients (SS-SGEC). The peroxisome-proliferator-activated receptor-γ (PPARγ) mediates important anti-inflammatory activities in epithelial cells. Herein, the comparative analysis of SG biopsies and SGEC lines obtained from SS patients and controls had revealed constitutively reduced PPARγ expression, transcriptional activity and anti-inflammatory function in the ductal epithelia of SS patients that were associated with cell-autonomously activated NF-κB and IL-1β pathways. Transcriptome profiling analysis revealed several differentially expressed proinflammatory and metabolism-related gene sets in SS-SGEC lines. These aberrations largely correlated with the severity of histopathologic lesions, the disease activity and the occurrence of adverse manifestations in SS patients studied, a fact which corroborates the key role of the persistently-activated epithelia in the pathogenesis of both local and systemic features of this disease. The treatment of control SGEC lines with PPARγ agonists was found to diminish the NF-κB activation and apoptosis induced by proinflammatory agents. In addition, the in-vitro application of PPARγ agonists and pharmacologic inhibitors of IL-1β and NF-κB had significant beneficial effects on SS-SGEC lines, such as the restoration of PPARγ functions and the reduction of their intrinsic activation, a fact which may advocate the future clinical study of the above agents as therapeutic modalities for SS. | |
| 28093418 | Cell-specific epigenome-wide DNA methylation profile in long-term cultured minor salivary | 2017 Mar | OBJECTIVES: The aetiology of primary Sjögren's syndrome (pSS), also referred to as autoimmune epithelitis, is incompletely understood but includes an epigenetic contribution. Accordingly, the aim of this study was to investigate DNA methylation in salivary gland epithelial cells (SGEC), and to compare results with those publicly available from pSS B and T cells. METHODS: Long-term cultured SGEC were selected to conduct an epigenome-wide association study (EWAS) in patients with pSS with comparison to controls using the HumanMethylation 450 K array from Illumina. RESULTS: The analysis of differentially methylated CpG (DMC) uncovered 4662 positions corresponding to 2560 genes, and 575 genes with two or more DMC sites (DMCs), in SGEC as compared with controls. Further analysis highlighted an important proportion of interferon-regulated genes (61%), the calcium pathway (hypomethylated) and the Wnt pathway (hypermethylated). When comparing SGEC with pSS T and/or B cell results, an important overlap was observed with respect to differentially methylated genes (38.8%) and pSS risk factors (71.4%), although such assertion was not true when comparing DMCs. CONCLUSIONS: This study conducted in SGEC emphasises the role of DNA methylation in pSS pathogenesis and supports the necessity to conduct pure cell analysis for future EWAS studies when analysing salivary glands from patients with pSS. | |
| 29089045 | A young female presenting with unilateral sacroiliitis following dengue virus infection: a | 2017 Nov 1 | BACKGROUND: Dengue is a common arthropod-borne viral infection in Sri Lanka which is spread by the mosquitos of the genus Aedes. The clinical features of dengue include high-grade fever associated with arthralgia and myalgia. However, dengue virus is not considered an arthritogenic virus. We report a case of a previously healthy young female who presented with imaging-confirmed right-sided sacroiliitis 10 days after developing dengue fever. This is the first reported case that shows a possible link between dengue infection and development of arthritis. CASE PRESENTATION: A 14-year-old Sri Lankan female presented to our medical unit with right buttock and hip pain of 3 weeks' duration. She had serologically confirmed dengue infection 10 days prior to the onset of buttock pain. A clinical examination revealed features of right sacroiliitis. An X-ray of her sacroiliac joint showed joint space widening and reactive bone changes. Magnetic resonance imaging of her pelvis and sacroiliac joint confirmed the diagnosis of acute sacroiliitis. She had an erythrocyte sedimentation rate of 110 mm first hour with a normal C-reactive protein. Her human leukocyte antigen-B27, rheumatoid factor, antinuclear antibody, chikungunya antibody, hepatitis serology, Brucella serology, and tuberculin skin test were negative. She was treated with nonsteroidal anti-inflammatory drugs and showed gradual improvement. CONCLUSIONS: After excluding possible causes for sacroiliitis, we postulated that sacroiliitis in the index case could have been caused or triggered by dengue virus infection. However there is a possibility that the sacroiliitis merely coincided with the dengue virus infection. This case illustrates the possibility that dengue virus could have a link with the development of arthritis in the same manner as other arthritogenic viruses; possible mechanisms for this include direct invasion of the synovium and the joint tissue by the virus, immune complex formation and deposition in the joint tissue, and immune dysregulation. Further studies are needed in this field to gain more knowledge, as dengue infection is highly prevalent in Sri Lanka. | |
| 28367662 | Adverse drug reactions after intravenous rituximab infusion are more common in hematologic | 2017 Nov | Rituximab is an effective treatment for CD20 + B-cell malignancies and autoimmune disorders. However, adverse drug reactions (ADRs) may occur after rituximab infusion, causing, in rare cases, its discontinuation. In this multicenter, retrospective study, among 374 patients treated with rituximab i.v., 23.5% experienced ADRs. Mean follow-up was 20.6 months (range 8-135). Overall, ADRs were significantly more frequent in non-Hodgkin lymphomas (NHL) and chronic lymphocytic leukemias (25-35.9%), than in autoimmune diseases (9.4-17.5%) (p < .0001). Grade 3-4 toxicity was observed in eight patients (2.1%), and in four of them (1% of all patients) definitive drug discontinuation was necessary. Interestingly, three groups of patients with different risk of developing ADR were identified, according to a predictive heat-map developed combining four parameters (splenomegaly, history of allergy, hemoglobin levels and gender) selected by multivariate analysis. This model may be useful in identifying patients at higher risk of ADRs, needing appropriate preventing therapies. |