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ID PMID Title PublicationDate abstract
25881761 The association of Tyro3/Axl/Mer signaling with inflammatory response, disease activity in 2015 Jul OBJECTIVES: Defects in Tyro3/Axl/Mer signaling may lead to impaired phagocytosis of apoptotic cells, eventually contributing to the development of autoimmune disease. The association of TAM signaling with several autoimmune disease has been investigated, but it remains unclear in primary Sjögren's syndrome. Therefore, the aim of this study was to evaluate the level of TAM signaling in primary Sjögren's syndrome with its clinical significance. METHODS: Real-Time Polymerase Chain Reaction was used to determine the mRNA expression of Mer, Tyro-3, Axl, Gas6, and Protein S in Peripheral Blood Mononuclear Cell from 43 pSS and 46 control. The Enzyme-Linked Immunosorbent Assay method was used to test plasma levels of soluble TAM signaling from those individuals, and the relationship of their levels with clinical characteristic was evaluated. RESULTS: The mRNA expression levels of Tyro-3, Axl were decreased in pSS patients. When considering the plasma level, increased levels of soluble Mer was observed with statistically significant difference. Soluble Mer levels were positively correlated with IgG levels (r=0.53, P<0.01), Erythrocyte Sedimentation Rate levels (r=0.44, P<0.01) and Sjögren's Syndrome Disease Activity Index (r=0.48, P<0.01). And the levels of soluble Mer in patients with the presence of SSA/SSB were higher than those without SSA/SSB. CONCLUSIONS: The plasma levels of sMer were increased in pSS patients, which was associated with inflammatory response and disease activity.
25635992 Effects of total glucosides of peony on AQP-5 and its mRNA expression in submandibular gla 2015 Jan OBJECTIVE: The aim of this study was to observe the effects of total glucosides of peony (TGP) on pathological change, Aquaporin-5 (AQP-5) and its mRNA expression in submandibular glands of non-obese diabetic (NOD) mice with Sjogren's Syndrome, to investigate its regulation on secretion of salivary glands. MATERIALS AND METHODS: 40 NOD mice were randomly divided into model group, TGP group, hydroxychloroquine group, combination group (n = 10). For TGP group, the mice were intragastrically administrated with 0.4 ml TGP dilution per day in accordance with 300 g/kg dose; for hydroxychloroquine group, the mice were intragastrically administrated with 0.4 ml hydroxychloroquine per day in accordance with 60 mg/kg dose; for the combination group, the mice were intragastrically administrated with 0.4 ml TGP dilution and 0.4 ml hydroxychloroquine. 8 weeks later, the mice were sacrificed, and submandibular glands were collected by anatomy. Pathological changes of submandibular gland were observed under a light microscope; AQP-5 protein in submandibular glands was detected by immunohistochemical staining; and AQP-5 mRNA expression in submandibular glands was detected by RT-PCR. RESULTS: The lymphocytic infiltration score of model mice was significantly higher than that of other groups. The pathological morphology and score of NOD mice were significantly improved after administration, and the combination group was superior to the hydroxychloroquine group and TGP group (p < 0.05). AQP-5 mRNA expression level of the model group was lower than other groups (p < 0.05); the expression levels in the TGP group and the combination group were higher than the hydroxychloroquine group (p < 0.05). CONCLUSIONS: TGP may improve pathological damage of submandibular glands of NOD mouse with Sjogren's syndrome by upregulating AQP-5 and its mRNA expression in submandibular glands.
25622919 Predominant Glandular Cholinergic Dysautonomia in Patients With Primary Sjögren's Syndrom 2015 May OBJECTIVE: The autonomic nervous system (ANS) modulates exocrine gland function. Available data show poor correlation between the degree of function and destruction of the exocrine glands in primary Sjögren's syndrome (SS), suggesting that other mechanisms, such as autonomic dysfunction, may be important in these patients. The aim of this study was to perform a comprehensive analysis of sympathoneural and sympathetic cholinergic function in well-characterized patients with primary SS. METHODS: Twenty-one patients with primary SS (mean ± SEM age 44.2 ± 2.8 years) and 13 healthy control subjects (mean ± SEM age 50.8 ± 1.9 years) were assessed during orthostasis and intravenous injection of edrophonium (10 mg). The postganglionic sympathetic cholinergic system was evaluated by assessing sweat production by means of the Quantitative Sudomotor Axon Reflex Test (QSART). Tests of gastric emptying were used to assess the gastrointestinal ANS in primary SS patients. RESULTS: The velocity index and the acceleration index were significantly higher (P < 0.05) in patients with primary SS as compared to controls, both before and during the orthostatic and edrophonium tests. Findings of other hemodynamic and neurochemical parameters did not differ between primary SS patients and controls during the orthostasis and edrophonium test; however, the edrophonium-induced saliva increment was lower in primary SS patients (P = 0.002). Abnormally low sweat production was found in 4 primary SS patients but in none of the controls, as determined by the QSART. Gastric empting was delayed in 53% of primary SS patients. CONCLUSION: We observed subtle differences in several ANS domains, including the gastrointestinal and sympathocholinergic systems, suggesting the presence of a complex ANS dysfunction in primary SS. The impact was greatest on the exocrine glands, with subtle differences in the cardiac parasympathetic function that were independent of glandular inflammation and atrophy, suggesting an alternative mechanism of disease pathogenesis in primary SS.
27580143 Diagnostic performance of MR imaging of three major salivary glands for Sjögren's syndrom 2017 Jan OBJECTIVE: We analyzed the diagnostic performance of the MR imaging findings of the parotid, submandibular, and sublingual glands to discriminate between patients with and without Sjögren's syndrome. METHODS: We retrospectively analyzed the correlation between the MR imaging and histopathological findings obtained from 69 patients with clinically suspected Sjögren's syndrome. We evaluated the heterogeneous signal intensity distribution on T1- and T2-weighted images, the multiple high-signal-intensity spots on MR sialograms, and the volume of the parotid, submandibular, and sublingual salivary glands. RESULTS: The multiple high-signal-intensity spots in the parotid gland showed the highest sensitivity and diagnostic accuracy (82% and 83%, respectively). In addition, the multiple high-signal-intensity spots and the heterogeneous signal intensity distribution in the submandibular gland showed high specificity (100% and 88%, respectively). The volume of the submandibular gland, but not that of the parotid or sublingual gland, was smaller in patients with Sjögren's syndrome. CONCLUSIONS: The presence of multiple high-signal-intensity spots on an MR sialogram in the parotid gland should be considered the best diagnostic indicator for Sjögren's syndrome. The presence of spots, heterogeneity, and the change to smaller volumes in the submandibular gland were also helpful because of their high specificity, particularly in advanced cases.
27214260 Endostatin is higher and associated with pulmonary involvement in primary Sjögren's syndr 2016 Jul OBJECTIVES: To investigate serum levels of endostatin in a well characterised cohort of patients with primary Sjögren's syndrome (pSS) and healthy controls (HC) and assess associations between these mediators and clinical parameters. METHODS: All patients (n=144) were recruited from the Norwegian systemic connective tissue disease and vasculitis registry (NOSVAR) and fulfilled American-European classification criteria for pSS. Pulmonary involvement was based on clinical symptoms and abnormal findings on high-resolution computed tomography of the lungs. The controls were 100 healthy blood donors. Serum levels of endostatin was determined by enzyme immunoassay. RESULTS: We found higher mean levels of serum endostatin in patients with pSS compared with the controls (p<0.001). The patients with interstitial lung disease (ILD) had higher levels compared with those without pulmonary involvement. CONCLUSIONS: Our results indicate that endostatin is increased in patients with pSS and particularly in those with ILD.
27196149 Sporadic occurrence of non-diagnosed IgG4-related disease in lymphoma patients with a prev 2016 Sep BACKGROUND: IgG4-related disease (IgG4-RD) is a recently recognized fibro-inflammatory disorder, which may affect many organs, and often comes to clinical attention due to tumor-like organ swelling or is identified incidentally by specific biopsy findings. Typical histopathology of IgG4-RD is lymphoplasmacytic infiltration rich in IgG4 + plasma cells (PCs), storiform fibrosis, and obliterative phlebitis. Patients with sicca symptoms can be misdiagnosed as primary Sjögren's syndrome (pSS) instead of IgG4-RD because of clinical and histopathological similarities. Moreover, an association with lymphoma development is described in both diseases. This study investigated signs of IgG4-RD in a population-based cohort of patients diagnosed with pSS complicated by lymphoma. METHODS: Patients with pSS and lymphoma diagnoses and available lymphoma specimens were identified by linkage with the Swedish Patient Register 1964-2007 and the Cancer Register 1990-2007 (n = 79). Clinical data and lymphomas were reviewed and the diagnoses evaluated. All lymphoma tissues and available minor salivary gland biopsies (n = 11) were immunostained for IgG4 + PCs and evaluated for other histopathological signs of IgG4-RD. In a case with specific findings of IgG4-RD, other available tissue specimens of the same patient were investigated for IgG4-RD. RESULTS: Only one patient of 79 (1.3%) had >10 IgG4 + PCs/high power field (HPF) in the lymphoma tissue, an unspecified low-grade B-cell lymphoma localized in the submandibular gland. This patient also had other histopathological features of IgG4-RD in the lymphoma and a surgical lung biopsy taken five years before lymphoma diagnosis and, therefore, fulfilled the criteria for IgG4-RD. Occasional IgG4 + PCs (<10/HPF) without signs of IgG4-RD were observed in another six lymphomas. No IgG4 + PCs were identified in the minor salivary gland biopsies. CONCLUSION: Histopathological findings of IgG4-RD may co-exist with low malignant B-cell lymphoma in patients with initially suspected pSS and may be associated with an underlying IgG4-RD.
26672682 Macrophage activation syndrome complicating adult onset Still's disease: A single center c 2016 Jun OBJECTIVES: Macrophage activation syndrome (MAS) is a life-threatening condition that can complicate adult onset Still's disease (AOSD). Due to its rarity, there is no clear consensus concerning treatment recommendations and outcomes. We studied the clinical manifestations and outcomes of a relatively large cohort of patients with MAS and AOSD, and compared the data with the literature reports. METHODS: We performed a retrospective review of 7 adult patients with MAS complicating AOSD at the Cleveland Clinic (CCF) over 7 years. All patients underwent bone marrow biopsies. Through MEDLINE and PubMed literature searches, we identified 48 cases of MAS/AOSD. We compared the data of the CCF and literature cohorts. RESULTS: We identified 7 patients with MAS complicating AOSD (6 females and 1 males) for our CCF cohort, with 4 cases simultaneously presenting with MAS and AOSD. The mean age at diagnosis of MAS was 41.9 ± 20.2 years and mean follow-up time was 18.6 ± 16.0 months. All patients had fever, arthralgias, and typical rash; 6 had leukocytosis, 4 had sore throat, and 3 had lymphadenopathy. These patients with AOSD also had MAS, with renal insufficiency and disseminated intravascular coagulation in 4, lung involvement in 3, and serositis and shock in 2. There was significant hepatic dysfunction in all patients and 6 had bi-cytopenias. At onset of MAS, all 7 patients had active AOSD. In addition to systemic glucocorticoids, 5 patients received anakinra, with 3 patients receiving combination therapy with cyclosporine. We also identified 48 cases (35 females and 13 males) for the literature cohort with the mean age at diagnosis of MAS of 40.2 ± 16.0 years and mean follow-up time of 17.5 ± 32.3 months. While the 2 cohorts were similar clinically, in the CCF cohort, more patients had renal insufficiency (p < 0.001), higher soluble IL-2 receptor level (p = 0.01), and lower ESR (p = 0.02) as compared with the literature cohort. All of our patients survived with a better outcome than the literature cohort. CONCLUSION: MAS can be a serious complication of active AOSD. Our study of a relatively large cohort in conjunction with literature suggests that prompt recognition and treatment with early addition of anakinra, systemic glucocorticoids, and cyclosporine as a triple regimen may improve clinical outcomes.
25976199 Tocilizumab for refractory organising pneumonia associated with Sjögren's disease. 2015 May 14 Lung involvement in primary Sjögren syndrome occurs in approximately 10-20% of patients. Tocilizumab, an anti-interleukin-6 receptor antibody, has demonstrated efficacy and safety in small series of systemic sclerosis, and systemic lupus erythematosus, but its effect on interstitial lung manifestations of connective tissue diseases is not well known. We report the use of tocilizumab in a refractory organising pneumonia associated with Sjögren's disease. Our observation suggests that tocilizumab could be an alternative therapeutic in refractory organising pneumonia.
25775148 Possible involvement of epithelial-mesenchymal transition in fibrosis associated with IgG4 2015 Sep OBJECTIVE: Immunoglobulin G4 (IgG4)-related Mikulicz's disease (MD) is a fibrosis-associated inflammatory disease, often accompanied by lacrimal gland swelling. Although much attention has been paid to the inflammatory aspects of this disease, the mechanisms of the fibrotic processes are still unclear. We focused on the fibrotic changes occurring in the lacrimal glands of IgG4-related MD patients, by examining molecules involved in the epithelial-mesenchymal transition (EMT). METHODS: Lacrimal gland tissue specimens were obtained from 3 IgG4-related MD patients and 3 control patients with Sjögren's syndrome (SS). The glands were examined by immunohistochemistry and transmission electron microscopy. RESULTS: Storiform fibrosis, a characteristic of IgG4-related MD, was observed in the lacrimal glands of IgG4-related MD, but rarely in those of SS. Reduced E-cadherin expression, increased phalloidin-stained filamentous actin, and increased α-smooth muscle actin, snail, and heat-shock protein 47 levels were observed in the lacrimal glands of IgG4-related MD compared with those of SS. Transmission electron microscopy revealed an abnormal periodicity of collagen bundles, and basal membrane thickening in the IgG4-related MD compared with that in the SS tissues. CONCLUSION: EMT-like changes were frequently observed in the lacrimal gland epithelia from patients with IgG4-related MD. Thus, EMT may be involved in the pathology of IgG4-related MD fibrosis.
25539431 Refractory primary Sjögren syndrome successfully treated with bortezomib. 2015 Jan Primary Sjögren syndrome (PSS) is a chronic autoimmune disease characterized by sicca complex and various systemic manifestations. Although it is well accepted to use corticosteroids for the treatment of systemic manifestations, there is scarce information available regarding the use of targeted therapy for refractory cases. We describe a case of a severe PSS patient refractory to conventional treatment with a response to bortezomib, a proteasome inhibitor commonly used for the treatment of multiple myeloma. Bortezomib administration resulted in a notable improvement of the general symptoms, particularly fatigue, and a decrease in serum globulin levels as well as in serum viscosity. Hyperglobulinemic purpura disappeared, and prednisone tapering succeeded. Because of chronicity, no clinical changes were observed in sicca symptoms. As far as we know, this is the first report on the use of bortezomib in a refractory case of PSS.
25222653 Incident cases of primary Sjögren's syndrome during a 5-year period in Stockholm County: 2015 OBJECTIVES: To define the incidence rate of primary Sjögren's syndrome (pSS) and the prevalence of extraglandular manifestations (EGMs) at the time of diagnosis of pSS in a prospective, population-based manner. METHOD: This study included all consecutive patients referred to the Department of Rheumatology at Karolinska University Hospital for the investigation of incident pSS from 1 January 2007 to 31 December 2011. Investigation was according to the current criteria for pSS, and examination with a focus on the presence of EGMs was performed. RESULTS: Of the referred individuals, 199 out of 781 were diagnosed with pSS. We found an annual incidence rate of pSS in the Karolinska University Hospital catchment area of 3.1 [95% confidence interval (CI) 2.3-4.3] cases per 100 000 adult inhabitants. The female/male ratio of incident cases was 14/1 [frequency (female) = 0.93, 95% CI 0.89-0.96]. In our cohort, we noted lower figures for severe EGMs such as lung and neurological involvement than previously reported for prevalent pSS. The frequency of autoantibodies including antinuclear antibodies (ANA), anti-Ro/SSA, and anti-La/SSB was also lower compared to other cohorts. In our study, autoantibody-positive patients had cytopaenia significantly more often, and in patients older than 60 years primary biliary cirrhosis (PBC) was more common. CONCLUSIONS: The incidence rate of pSS is 3.1 (95% CI 2.3-4.3) per 100 000 person-years. The prevalence of autoantibodies may be lower than previously reported, and at diagnosis, patients with pSS have few severe EGMs.
27180497 Controlling joint pain in older people. 2016 Jan Jont pain in oldder people The prevalence of chronic pain in older people in the community ranges from 25 to 76% and for those in residential care, it is even higher at 83 to 93%. The most common sites affected are the back, hip, or knee, and other joints. There is increased reporting of pain in women (79%) compared with men (53%). Common conditions include osteoarthritis and, to a lesser extent, the inflammatory arthropathies such as rheumatoid arthritis. The differential diagnosis includes non-articular pain such as vascular limb pain and nocturnal cramp, some neuropathic pain conditions (such as compressive neuropathies and postherpetic neuralgia), soft tissue disorders such as fibromyalgia and myofascial pain syndromes. In addition to an assessment of pain intensity, a biopsychosocial model should be adopted to ascertain the effect of the pain on the patient's degree of background pain at rest. The disease is often localised to the large load-bearing joints, predominantly the hips and knees. In contrast to osteoarthritis, the inflammatory arthritides typically present with symmetrical swollen, stiff, and painful small joints of the hands and feet, usually worse in the morning.
27556236 Asymptomatic Atherosclerosis in Primary Sjögren Syndrome: Correlation Between Low Ankle B 2016 Sep BACKGROUND: Primary Sjögren syndrome is a chronic inflammatory autoimmune disease. The delay in diagnosis allows the establishment of a chronic inflammatory state, which makes primary Sjögren syndrome an interesting model for the study of atherosclerosis. OBJECTIVES: The aim of this study was to evaluate subclinical atherosclerosis in 49 patients with Sjögren syndrome using noninvasive methods. METHODS: We assessed traditional risk factors such as hypertension, diabetes, dyslipidemia, smoking, and family history of atherosclerosis. Patients with prior cardiovascular events and a history of atherosclerosis were excluded. Clinical and laboratory features were recorded, as well as the European League Against Rheumatism Sjögren's Syndrome Activity Index calculation. The atherosclerosis evaluation was done by carotid intima-media thickness, measured by ultrasonography, and ankle-brachial index (ABI). RESULTS: Fifteen patients (31%) had at least 1 traditional risk factor, and 65.3% had a European League Against Rheumatism Sjögren's Syndrome Activity Index score from mild to moderate. Only 2 patients had increased carotid intima-media thickness. However, 59% presented ABI alterations. Multiple correspondence analysis showed a clear correlation between low ABI and the positivity of autoantibodies (antinuclear antibodies, anti-SSA, rheumatoid factor). CONCLUSIONS: The subgroup of patients with positive autoantibodies showed low ABI, which may represent a higher risk of early atherosclerosis and indicate the need for more careful monitoring in this group.
27523010 Limbic Encephalitis Associated with Sjögren's Syndrome: Report of Three Cases. 2016 Sjögren's syndrome (SS) may be complicated by neurological manifestations. We herein report three women (age range 26-60 years old) who all presented with limbic encephalitis (LE) as the predominant clinical feature 3 months to 15 years after the diagnosis of SS. The 26-year-old patient also developed acute motor axonal neuropathy one week after autoimmune encephalitis. All three patients showed contrast-enhanced MRI lesions and inflammatory cerebrospinal fluid findings, while not displaying any anti-neuronal antibodies and showing a remarkable response to immunotherapy. SS is often overlooked when the symptoms are mild. Therefore, in LE cases with no identifiable cause, serological screening for rheumatologic disorders is recommended.
25887888 Clinical characteristics and biopsy accuracy in suspected cases of Sjögren's syndrome ref 2015 Feb 15 BACKGROUND: Labial salivary gland biopsy (LSGB) is the most important diagnostic tool for the diagnosis of Sjögren's syndrome (SS), but its diagnostic value is rarely studied. This study assessed the sensibility and specificity of LSGB, and the clinical profiles of patients who were referred for biopsy. METHODS: Retrospective analysis of the histopathological reports from LSGB and medical report data from patients who underwent LSGB between 2008 and 2011 was conducted. RESULTS: About 290 biopsies were performed and 74 were excluded due to insufficient clinical data. Of the 216 patients, 0.46% was carrier of hepatitis C virus, 30.1% had primary SS (pSS), and 8.8% had secondary SS (sSS). Of the samples, 94.3% presented dryness symptoms, 51.6% experienced dryness only, 42.7% had systemic manifestations, and 66.9% presented low unstimulated salivary flow and/or Schirmer's test. LSGB was necessary in 67.6% to confirm the presence of SS based on the American-European Consensus Group 2002 criteria (AECG). Based on specialist's opinion, sensibility level was 86.57%, and specificity was 97.43%. Positive predictive value (PPV) was 95%, and negative predictive value (NPV) was 92.6%. Determined accuracy was 93.3%. Concordance (kappa coefficient) of LSGB and specialist's opinion was 0.851, and LSGB with AECG criteria was 0.806. Of the 98 patients referred with fibromyalgia and dryness, 36.7% had SS and LSBG focus score of ≥ 1. Patients with SS were older, and showed more severe lachrymal and salivary dysfunctions, greater frequency of fibromyalgia, anti-nuclear antibodies (ANA), anti-SSA-Ro, and anti-SSB-La. CONCLUSIONS: Labial salivary gland biopsy has high sensibility, specificity, positive and negative predictive values for diagnosis of pSS. In the clinical practice, it is useful, especially for those patients with glandular dysfunctions and negative antibodies.
25557346 Potentially pathogenic immune cells and networks in apparently healthy lacrimal glands. 2015 Jan Lacrimal glands of people over 40 years old frequently contain lymphocytic infiltrates. Relationships between histopathological presentation and physiological dysfunction are not straightforward. Data from rabbit studies have suggested that at least two immune cell networks form in healthy lacrimal glands, one responding to environmental dryness, the other to high temperatures. New findings indicate that mRNAs for several chemokines and cytokines are expressed primarily in epithelial cells; certain others are expressed in both epithelial cells and immune cells. Transcript abundances vary substantially across glands from animals that have experienced the same conditions, allowing for correlation analyses, which detect clusters that map to various cell types and to networks of coordinately functioning cells. A core network--expressing mRNAs including IL-1α, IL-6, IL-17A, and IL-10--expands adaptively with exposure to dryness, suppressing IFN-γ, but potentially causing physiological dysfunction. High temperature elicits concurrent increases of mRNAs for prolactin (PRL), CCL21, and IL-18. PRL is associated with crosstalk to IFN-γ, BAFF, and IL-4. The core network reacts to the resulting PRL-BAFF-IL-4 network, creating a profile reminiscent of Sjögren's disease. In a warmer, moderately dry setting, PRL-associated increases of IFN-γ are associated with suppression of IL-10 and augmentations of IL-1α and IL-17, creating a profile reminiscent of severe chronic inflammation.
26644910 Treatment of bone marrow lesions (bone marrow edema). 2015 Bone marrow lesions (BMLs) or using older terminology 'Bone marrow edema' is characterised by excessive water signals in the marrow space on magnetic resonance imaging or ultrasound; BMLs constitute a central component of a wide variety of inflammatory and non-inflammatory rheumatologic conditions affecting the musculoskeletal system: BMLs are not only considered significant sources of pain but also linked to increased disease activity in many musculoskeletal conditions (for example, osteoarthritis, rheumatoid arthritis). The purpose of this review is to summarise current knowledge about the treatment of BMLs, with an emphasis on the clinical and histological features of this entity in inflammatory and non-inflammatory disease. We also try to pair this hypothesis with the apparent beneficial effects of various treatment regimens, mainly within the group of bone antiresorptive drugs (calcitonin, bisphosphonates) on symptoms associated with BMLs.
27622149 Femoro Patella Vialla patellofemoral arthroplasty: An independent assessment of outcomes a 2016 Aug 18 AIM: To determine outcomes using the Femoro-Patella Vialla (FPV) arthroplasty and if there is an ideal patient for this implant. METHODS: A total of 41 FPV patellofemoral joint replacements were performed in 31 patients (22 females, 9 males, mean age 65 years). Mean follow-up was 3.2 years (minimum 2 years). Radiographs were reviewed preoperatively and postoperatively. We assessed whether gender, age, previous surgery, patella atla or trochlear dysplasia influenced patient satisfaction or patient functional outcome. RESULTS: The median Oxford Knee Score was 40 and the median Melbourne Patellofemoral Score was 21 postoperatively. Seventy-six percent of patients were satisfied, 10% unsure and 14% dissatisfied postoperatively. There was no radiological progression of tibiofemoral joint arthritis, using the Ahlback grading, in any patient. One patient, who was diagnosed with rheumatoid arthritis postoperatively, underwent revision to total knee replacement. There were no intraoperative lateral releases and no implant failures. Gender, age, the presence of trochlear dysplasia, patella alta or bilateral surgery did not influence patient outcome. Previous surgery did not correlate with outcome. CONCLUSION: In contrast to the current literature, the FPV shows promising early results. However, we cannot identify a subgroup of patients with superior outcomes.
27775097 Involvement of P2X7 receptor signaling on regulating the differentiation of Th17 cells and 2016 Oct 24 Interleukin (IL)-17 producing T helper (Th17) cells are major effector cells in the pathogenesis of rheumatoid arthritis (RA). The P2X7 receptor (P2X7R) has emerged as a potential site in the regulation of inflammation in RA but little is known of its functional role on the differentiation of Th17 cells. This study investigates the in vitro and in vivo effects of P2X7R on Th17 cell differentiation during type II collagen (CII) induced experimental arthritis model. In CII-treated dendritic cells (DCs) and DC/CD4(+) T coculture system, pretreatment with pharmacological antagonists of P2X7R (Suramin and A-438079) caused strong inhibition of production of Th17-promoting cytokines (IL-1β, TGF-β1, IL-23p19 and IL-6). Exposure to CII induced the elevation of mRNAs encoding retinoic acid receptor-related orphan receptor α and γt, which were abolished by pretreatment with P2X7R antagonists. Furthermore, blocking P2X7R signaling abolished the CII-mediated increase in IL-17A. Blockade of P2X7R remarkably inhibited hind paw swelling and ameliorated pathological changes in ankle joint of the collagen-induced arthritis mice. Thus, we demonstrated a novel function for P2X7R signaling in regulating CII-induced differentiation of Th17 cells. P2X7R signaling facilitates the development of the sophisticated network of DC-derived cytokines that favors a Th17 phenotype.
27313839 Epithelium-specific Ets transcription factor-1 acts as a negative regulator of cyclooxygen 2016 BACKGROUND: Rheumatoid arthritis (RA) is characterized by excessive synovial inflammation. Cyclooxygenase-2 (COX-2) is an enzyme that catalyzes the conversion of arachidonic acid (AA) into prostaglandins. Epithelium-specific Ets transcription factor-1 (ESE-1) was previously demonstrated to upregulate COX-2 in co-operation with nuclear factor kappa B (NFκB) in macrophages and chondrocytes. However, the role of ESE-1 in RA pathology has remained unclear. In this study, we aimed to elucidate the relationship between ESE-1 and COX-2 in RA synovial fibroblasts (RASFs) using a HD-Ad-mediated knockdown approach. RESULTS: ESE-1 and COX-2 were induced by IL-1β in RASFs that corresponded with an increase in PGE2. Endogenous levels of ESE-1 and COX-2 in human RASFs were analyzed by RT-qPCR and Western blot, and PGE2 was quantified using competitive ELISA. Interestingly, knockdown of ESE-1 using helper-dependent adenovirus (HD-Ad) led to a significant upregulation of COX-2 at a later phase of IL-1β stimulation. Examination of ESE-1 intracellular localization by nuclear fractionation revealed that ESE-1 was localized in the nucleus, occupying disparate cellular compartments to NFκB when COX-2 was increased. To confirm the ESE-1-COX-2 relationship in other cellular systems, COX-2 was also measured in SW982 synovial sarcoma cell line and ESE-1 knockout (KO) murine macrophages. Similarly, knockdown of ESE-1 transcriptionally upregulated COX-2 in SW982 and ESE-1 KO murine macrophages, suggesting that ESE-1 may be involved in the resolution of inflammation. CONCLUSION: ESE-1 acts as a negative regulator of COX-2 in human RASFs and its effect on COX-2 is NFκB-independent.