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ID PMID Title PublicationDate abstract
27421127 [Pulmonary involvement in connective tissue disease]. 2016 The connective tissue diseases are a variable group of autoimmune mediated disorders characterized by multiorgan damage. Pulmonary complications are common, usually occur after the onset of joint symptoms, but can also be initially presenting complaint. The respiratory system may be involved in all its component: airways, vessels, parenchyma, pleura and respiratory muscles. Lung involvement is an increasing cause of morbidity and mortality in the connective tissue diseases. Clinical course is highly variable - can range from mild to rapidly progressive, some processes are reversible, while others are irreversible. Thus, the identification of reversible disease , and separately progressive disease, are important clinical issues. The frequency, clinical presentation, prognosis and responce to therapy are different, depending on the pattern of involvement as well as on specyfic diagnostic method used to identify it. High- resolution computed tompography plays an important role in identifying patients with respiratory involvement. Pulmonary function tests are a sensitive tool detecting interstitial lung disease. In this article, pulmonary lung involvement accompanying most frequently apperaing connective tissue diseases - rheumatoid arthritis, systemic sclerosis, lupus erythematosus, polymyositis/dermatomyositis, Sjögrens syndrome and mixed connective tissue disaese are reviewed.
25946084 Vitamin D for the treatment of chronic painful conditions in adults. 2015 May 6 BACKGROUND: This review is an update of a previously published review in the Cochrane Database of Systematic Reviews (Issue 1, 2010) on 'Vitamin D for the treatment of chronic painful conditions in adults'.Vitamin D is produced in the skin after exposure to sunlight and can be obtained through food. Vitamin D deficiency has been linked with a range of conditions, including chronic pain. Observational and circumstantial evidence suggests that there may be a role for vitamin D deficiency in the aetiology of chronic painful conditions. OBJECTIVES: To assess the efficacy and safety of vitamin D supplementation in chronic painful conditions when tested against placebo or against active comparators. SEARCH METHODS: For this update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and EMBASE to February 2015. This was supplemented by searching the reference lists of retrieved articles, reviews in the field, and online trial registries. SELECTION CRITERIA: We included studies if they were randomised double-blind trials of vitamin D supplementation compared with placebo or with active comparators for the treatment of chronic painful conditions in adults. DATA COLLECTION AND ANALYSIS: Two review authors independently selected the studies for inclusion, assessed methodological quality, and extracted data. We did not undertake pooled analysis due to the heterogeneity of the data. Primary outcomes of interest were pain responder outcomes, and secondary outcomes were treatment group average pain outcomes and adverse events. MAIN RESULTS: We included six new studies (517 participants) in this review update, bringing the total of included studies to 10 (811 participants). The studies were heterogeneous with regard to study quality, the chronic painful conditions that were investigated, the dose of vitamin D given, co-interventions, and the outcome measures reported. Only two studies reported responder pain outcomes; the other studies reported treatment group average outcomes only. Overall, there was no consistent pattern that vitamin D treatment was associated with greater efficacy than placebo in any chronic painful condition (low quality evidence). Adverse events and withdrawals were comparatively infrequent, with no consistent difference between vitamin D and placebo (good quality evidence). AUTHORS' CONCLUSIONS: The evidence addressing the use of vitamin D for chronic pain now contains more than twice as many studies and participants than were included in the original version of this review. Based on this evidence, a large beneficial effect of vitamin D across different chronic painful conditions is unlikely. Whether vitamin D can have beneficial effects in specific chronic painful conditions needs further investigation.
25575725 Methotrexate-mediated activation of an AMPK-CREB-dependent pathway: a novel mechanism for 2016 Feb AIMS: Premature cardiovascular events complicate chronic inflammatory conditions. Low-dose weekly methotrexate (MTX), the most widely used disease-modifying drug for rheumatoid arthritis (RA), reduces disease-associated cardiovascular mortality. MTX increases intracellular accumulation of adenosine monophosphate (AMP) and 5-aminoimidazole-4-carboxamide ribonucleotide which activates AMP-activated protein kinase (AMPK). We hypothesised that MTX specifically protects the vascular endothelium against inflammatory injury via induction of AMPK-regulated protective genes. METHODS/RESULTS: In the (NZW×BXSB)F1 murine model of inflammatory vasculopathy, MTX 1 mg/kg/week significantly reduced intramyocardial vasculopathy and attenuated end-organ damage. Studies of human umbilical vein endothelial cells (HUVEC) and arterial endothelial cells (HAEC) showed that therapeutically relevant concentrations of MTX phosphorylate AMPKα(Thr172), and induce cytoprotective genes including manganese superoxide dismutase (MnSOD) and haem oxygenase-1 (HO-1). These responses were preserved when HUVECs were pretreated with tumour necrosis factor-α to mimic dysfunctional endothelium. Furthermore, MTX protected against glucose deprivation-induced endothelial apoptosis. Mechanistically, MTX treatment led to cyclic AMP response element-binding protein (CREB)(Ser133) phosphorylation, while AMPK depletion attenuated this response and the induction of MnSOD and HO-1. CREB siRNA inhibited upregulation of both cytoprotective genes by MTX, while chromatin immunoprecipitation demonstrated CREB binding to the MnSOD promoter in MTX-treated EC. Likewise, treatment of (NZW×BXSB)F1 mice with MTX enhanced AMPKα(Thr172) phosphorylation and MnSOD, and reduced aortic intercellular adhesion molecule-1 expression. CONCLUSIONS: These data suggest that MTX therapeutically conditions vascular endothelium via activation of AMPK-CREB. We propose that this mechanism contributes to the protection against cardiovascular events seen in patients with RA treated with MTX.
27481899 Usefulness of IgA Anti-α-fodrin Antibodies in Combination with Rheumatoid Factor and/or A 2016 Oct OBJECTIVE: We aimed to evaluate the usefulness of anti-α-fodrin antibodies (AFA) in combination with rheumatoid factor (RF) and/or antinuclear antibodies (ANA) as an alternative immunological criterion for Sjögren syndrome (SS) among patients with negative anti-Ro/La serology. METHODS: The study included 350 patients (100 with rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis, and 50 with primary SS) randomly selected and assessed for SS. All patients were tested for ANA, RF, anti-SSA/SSB, and AFA antibodies. SS diagnosis was made on a clinical basis by 2 rheumatologists based on the 6-item screening questionnaire, Schirmer-I test, nonstimulated whole salivary flow rate, fluorescein staining test, autoantibodies, lip biopsy, and medical chart review. Non-SS was defined as lack of clinical diagnosis and not fulfilling the American-European Consensus Group classification criteria and the American College of Rheumatology (ACR) criteria. The ACR criteria were applied substituting the immunological criteria as follows: (1) RF plus ANA > 1:320, (2) RF plus AFA, (3) ANA > 1:320 plus AFA, (4) RF alone, and (5) 2 positive tests out of RF, ANA > 1:320, or AFA. We estimated the sensitivity, specificity, positive predictive value, negative predictive value, and likelihood ratio positivity with 95% CI for each criterion. RESULTS: There were 236 patients (67%) who tested negative for anti-SSA/SSB antibodies, of whom 65 (27.5%) were clinically diagnosed as SS, and 149 (63%) with non-SS. RF + AFA and ANA + AFA performed similarly to RF + ANA > 1:320. The model 2 out of 3 of RF, ANA, or AFA improved the sensitivity from 56.9% to 70.7%, although the specificity decreased. CONCLUSION: The combination AFA + RF, AFA + ANA > 1:320, or at least 2 out of 3, performed well as a proxy immunological test for patients with SS and negative Ro/La serology.
27708969 Rheumatoid arthritis and tabetic arthropathy: physiopathological link or simple associatio 2016 Mar To the best of our knowledge, the association of rheumatoid arthritis and tabetic arthropathy has never been described before in the literature. We report here a first observation. We report the case of a 50-year-old man, treated for syphilitic arthritis evolving for 4 years, who presented with a table of rheumatoid arthritis. The diagnosis of rheumatoid arthritis was established according to the 2010 American College of Rheumatology/European League Against Rheumatism criteria (ACR/EULAR). The treatment was based on weekly injection of methotrexate and a symptomatic treatment by corticosteroid. The association of rheumatoid arthritis and tabetic arthropathy is rare, to our knowledge this is the first case reported. This case reminds us that a neuropathic arthropathy as tabetic arthropathy, although it is rare, can be associated in a sporadic or exceptional way with other rheumatic disease like rheumatoid arthritis. A physiopathological link between the both diseases remains to be proved.
25711376 Central retinal vein occlusion caused by hyperviscosity syndrome in a young patient with S 2015 Jun We report in this article central retinal vein occlusion (CRVO) caused by hyperviscosity syndrome (HVS) in a young patient with mucosa-associated lymphoid tissue (MALT) lymphoma and Sjögren's syndrome (SjS). A 32-year-old female was referred to our hospital from a local ophthalmologist. Fundoscopic examination and fluorescein angiogram revealed she had a serous retinal detachment in the right eye, together with CRVO (nonischemic type) in both eyes. Systemic examinations revealed hyperglobulinemia, increased blood viscosity, increased antinuclear antibody, increased rheumatoid arthritis particle aggregation, and increased anti-SS-A antibody. Together with a decreased salivary gland secretory function, she was eventually diagnosed as suffering from SjS. Moreover, a large cystic mass was found in the anterior mediastinum on the chest X-ray. Fine needle biopsy soon revealed she had MALT lymphoma. After eight courses of the administration of rituximab, cyclophosphamide, vincristine, and prednisolone (R-CVP), most laboratory values were normalized, including blood viscosity. Cystic mass in the anterior mediastinum decreased, and the conditions of CRVO in both eyes had much improved. Decreased best-corrected visual acuity (BCVA) in the right eye was fully restored by sixth month. Not only MALT lymphoma, but also SjS can cause secondary hyperglobulinemia. Indeed, immunoelectrophoresis-serum test showed a polyclonal pattern of hyperglobulinemia. Therefore, SjS was thought to be the primary reason of hyperglobulinemia in this patient, which induced HVS, eventually causing CRVO. R-CVP therapy was effective for not only MALT lymphoma but also SjS accompanied with HVS. Consequently, R-CVP therapy led to the improvement of CRVO.
26225124 Is air pollution a risk factor for rheumatoid arthritis? 2015 Rheumatoid arthritis is a chronic inflammatory debilitating disease triggered by a complex interaction involving genetic and environmental factors. Active smoking and occupational exposures such as silica increase its risk, suggesting that initial inflammation and generation of rheumatoid arthritis-related autoantibodies in the lungs may precede the clinical disease. This hypothesis paved the way to epidemiological studies investigating air pollution as a potential determinant of rheumatoid arthritis. Studies designed for epidemiology of rheumatoid arthritis found a link between traffic, a surrogate of air pollution, and this disease. Furthermore, a small case-control study recently found an association between wood smoke exposure and anticyclic citrullinated protein/peptide antibody in sera of patients presenting wood-smoke-related chronic obstructive pulmonary disease. However, reports addressing impact of specific pollutants on rheumatoid arthritis incidence and severity across populations are somewhat conflicting. In addition to the link reported between other systemic autoimmune rheumatic diseases and particulate matters/gaseous pollutants, experimental observation of exacerbated rheumatoid arthritis incidence and severity in mice models of collagen-induced arthritis after diesel exhaust particles exposure as well as hypovitaminosis D-related autoimmunity can help understand the role of air pollution in rheumatoid arthritis. All these considerations highlight the necessity to extend high quality epidemiological researches investigating different sources of atmospheric pollution across populations and particularly in low-and-middle countries, in order to further explore the biological plausibility of air pollution's effect in the pathogenesis of rheumatoid arthritis. This should be attempted to better inform policies aiming to reduce the burden of rheumatoid arthritis.
26079682 Serum leucine-rich α2-glycoprotein is a useful biomarker for monitoring disease activity 2015 OBJECTIVE: To investigate whether serum leucine-rich α2-glycoprotein (LRG) levels are elevated in patients with adult-onset Still's disease (AOSD) and determine their correlation with disease activity parameters. METHOD: We enrolled 39 patients with AOSD, 47 patients with rheumatoid arthritis (RA), and 39 controls. Forty-five serum samples from the patients with AOSD were assayed for LRG using an enzyme-linked immunosorbent assay (ELISA). Comprehensive AOSD activity was determined by a modified Pouchot score. RESULTS: Serum LRG levels were significantly elevated in patients with AOSD (128.8±40.8 ng/mL) compared to those in patients with RA and in controls (33.9±15.2 ng/mL, p<0.001 and 22.4±6.1 ng/mL, p<0.001, respectively). Patients with active AOSD had significantly higher LRG levels than those with inactive disease (141.4±31.3 ng/mL vs. 79.8±37.1 ng/mL, p=0.002). Serum LRG levels were positively correlated with C-reactive protein (CRP; γ=0.387, p=0.015), lactate dehydrogenase (LDH; γ=0.370, p=0.026), ferritin (γ=0.687, p<0.001) levels, and the modified Pouchot score (γ=0.756, p<0.001). Serum LRG levels decreased significantly after treatment in all six patients with active AOSD who had follow-up evaluations (p=0.007). The best cut-off value for LRG to distinguish AOSD from RA was 67.9 ng/mL, with a sensitivity of 92.3% and a specificity of 97.9%. CONCLUSIONS: Serum LRG levels were increased in patients with AOSD and correlated well with disease activity measures. LRG may be a useful biomarker for distinguishing AOSD from RA and for monitoring the disease activity of AOSD.
26557378 Rheumatoid arthritis treatment: the earlier the better to prevent joint damage. 2015 The management of rheumatoid arthritis has undergone major advances in recent years, both in terms of the drugs armamentarium and therapeutic strategy. Treating disease to target, aiming at remission, through a tight control protocol is regarded as the standard of care. Reaching clinical and radiographic disease remission has therefore become an achievable goal. Increasing evidence has demonstrated that early diagnosis, prompt treatment initiation and early achievement of remission are the major predictors of long-term clinical, functional and radiographic outcomes. Concentrating efforts in controlling disease activity in a very early window of opportunity offers unique sustained benefits. In this short review, we analysed the available evidence supporting the value of treating rheumatoid arthritis early and the impact on disease outcomes, with particular focus on radiographic progression.
27749234 Sjögren's syndrome: managed care data from a large United States population highlight rea 2017 Jan OBJECTIVES: To better understand the real-world characteristics and costs of Sjögren's syndrome (SS). METHODS: Analysing the MarketScan Commercial Claims database from Jan. 1, 2006 to Dec. 31, 2011, we identified 10,414 patients ≥18 years old newly diagnosed with SS. Patient characteristics, drugs (commonly used for SS), resource utilisation, and medical costs were evaluated for 12 months pre- and post-diagnosis. RESULTS: Mean age was 55 years; 90% were female. At diagnosis, SS patients were most often seen by rheumatologists (39%) or internists (14.2%); the most common concurrent autoimmune conditions were rheumatoid arthritis (17.9%) and systemic lupus erythematosus (14.6%). Other common comorbidities were hypertension (37.6%), osteoarthritis (31.4%), and hyperlipidaemia/dyslipidaemia (30.3%). Post diagnosis of SS, claims for myocardial infarction and coronary artery bypass graft doubled. Medications of interest prescribed post-diagnosis were eye/mouth drugs (32.2%) and synthetic immunosuppressants (32.1%). Biologic drugs were prescribed to a minority (TNF inhibitors, ~5.0%; non-TNF inhibitors, 1%). Of note, prescriptions for all systemic immunotherapies (synthetic and biologic) were significantly lower in the subgroup without concurrent autoimmune disease, and 15.1% of the overall population had no SS-related prescriptions. Post diagnosis, total medical resource utilisation and total medical costs increased (1.2 and 1.4-fold, respectively). CONCLUSIONS: In this retrospective, real-world analysis, medical claims in the first year after SS diagnosis revealed that cardiovascular (CV) events increased and all-cause healthcare costs grew by 40%. Pharmacologic management consisted primarily of low potency immunomodulation and symptomatic treatments. Systemic disease-modifying therapies were used mostly in patients who had another concurrent autoimmune disease, suggesting a lack of treatment options for SS.
26385705 Association of CXCL10 and CXCL13 levels with disease activity and cutaneous manifestation 2015 Sep 19 INTRODUCTION: C-X-C motif chemokine 10 (CXCL10) is produced in response to interferon-γ, and tumor necrosis factor-α (TNF-α) triggers the accumulation of activated lymphocytes. CXCL13 is constitutively expressed in secondary lymphoid tissues, and the expression is upregulated by TNF-α, via T cell stimulation. It appears that CXCL10 and CXCL13 could play a potential role in the pathogenesis of adult-onset Still's disease (AOSD), therefore, we investigated the associations between CXCL10 and CXCL13 levels and clinical manifestations in patients with active AOSD. METHODS: Blood samples were collected from 39 active AOSD patients, 32 rheumatoid arthritis (RA) patients and 40 healthy controls (HC). Of the AOSD patients, follow-up samples were collected from 15 9.6 ± 9.2 months later. Serum levels of CXCL10 and CXCL13 were determined using enzyme-linked immunosorbent assay. CXCL10, CXCL13, and C-X-C chemokine receptor type 3 (CXCR3) expression levels in biopsy specimens obtained from 26 AOSD patients with skin rashes were investigated via immunohistochemistry. RESULTS: The CXCL10 levels in AOSD patients (1,031.3 ± 2,019.6 pg/mL) were higher than in RA (146.3 ± 91.4 pg/mL, p = 0.008) and HC (104.4 ± 47.9 pg/mL, p = 0.006). Also, the CXCL13 levels of AOSD patients (158.8 ± 151.2 pg/mL) were higher than those of RA (54.4 ± 61.1 pg/mL, p < 0.001) and HC (23.5 ± 18.1 pg/mL, p < 0.001). Serum CXCL10 levels correlated with ferritin and systemic scores. Serum CXCL13 levels correlated with those of hemoglobin, C-reactive protein, ferritin, and albumin, and systemic scores. In follow-up AOSD patients, the levels of CXCL10 and CXCL13 fell significantly (153.7 ± 130.1 pg/mL, p = 0.002, and 89.1 ± 117.4 pg/mL, p = 0.001, respectively). On immunohistochemistry, the percentages of inflammatory cells expressing CXCL10 ranged from 1 to 85%, CXCL13 from 1 to 72%, and CXCR3 from 2 to 65%. The percentage of CXCL10-positive inflammatory cells was higher in skin biopsy samples exhibiting mucin deposition than in those that did not (p = 0.01). CXCL13 levels were correlated with those of CD4 and CD68. CONCLUSIONS: Serum CXCL10 and CXCL13 levels may serve as clinical markers for assessment of disease activity in AOSD. CXCL10/CXCR3 and CXCL13 may contribute to the inflammatory response, especially skin manifestations thereof, in AOSD.
26547221 Serum calprotectin--a promising diagnostic marker for adult-onset Still's disease. 2016 Jan Calprotectin is a calcium-binding cytosolic protein, mainly expressed in immune cells, such as neutrophils, monocytes, and macrophages. Our study aimed to evaluate the diagnostic value of calprotectin for adult-onset Still's disease (AOSD), by comparing serum calprotectin concentrations in patients with AOSD (n = 46), rheumatoid arthritis (RA, n = 34), primary Sjögren syndrome (pSS, n = 40), systemic lupus erythematosus (SLE, n = 39), osteoarthritis (OA, n = 20), and healthy controls (HCs, n = 49). Calprotectin concentrations were significantly higher in patients with AOSD (55.26 ± 18.00 ng/ml), compared to patients with RA (39.17 ± 18.90 ng/ml), pSS (35.31 ± 19.47 ng/ml), SLE (32.21 ± 25.01 ng/ml), OA (19.24 ± 10.67 ng/ml), and HCs (8.46 ± 5.17 ng/ml). All the differences were highly significant (p < 0.001). Using receiver-operating characteristic curve, the cut-off value of calprotectin was defined as 45.488 ng/ml, and its sensitivity and specificity for AOSD diagnosis were 63.0 and 80.1%, respectively. The positive rate of calprotectin was significantly higher in AOSD cases compared to patients with other diseases and healthy controls (p < 0.001). Serum calprotectin was positively correlated with ferritin (r = 0.294, p < 0.05), and concentration of hemoglobin was significantly lower in calprotectin-positive patients compared to negative patients in AOSD (103.49 ± 20.21 g/l vs 115.71 ± 15.59 g/l, t = -2.142, p = 0.038). These findings suggest that serum calprotectin may serve as a promising marker for the diagnosis of AOSD and monitor disease activity to a certain extent.
27603155 Epidemiology of Fracture Nonunion in 18 Human Bones. 2016 Nov 16 IMPORTANCE: Failure of bone fracture healing occurs in 5% to 10% of all patients. Nonunion risk is associated with the severity of injury and with the surgical treatment technique, yet progression to nonunion is not fully explained by these risk factors. OBJECTIVE: To test a hypothesis that fracture characteristics and patient-related risk factors assessable by the clinician at patient presentation can indicate the probability of fracture nonunion. DESIGN, SETTING, AND PARTICIPANTS: An inception cohort study in a large payer database of patients with fracture in the United States was conducted using patient-level health claims for medical and drug expenses compiled for approximately 90.1 million patients in calendar year 2011. The final database collated demographic descriptors, treatment procedures as per Current Procedural Terminology codes; comorbidities as per International Classification of Diseases, Ninth Revision codes; and drug prescriptions as per National Drug Code Directory codes. Logistic regression was used to calculate odds ratios (ORs) for variables associated with nonunion. Data analysis was performed from January 1, 2011, to December 31, 2012. EXPOSURES: Continuous enrollment in the database was required for 12 months after fracture to allow sufficient time to capture a nonunion diagnosis. RESULTS: The final analysis of 309 330 fractures in 18 bones included 178 952 women (57.9%); mean (SD) age was 44.48 (13.68) years. The nonunion rate was 4.9%. Elevated nonunion risk was associated with severe fracture (eg, open fracture, multiple fractures), high body mass index, smoking, and alcoholism. Women experienced more fractures, but men were more prone to nonunion. The nonunion rate also varied with fracture location: scaphoid, tibia plus fibula, and femur were most likely to be nonunion. The ORs for nonunion fractures were significantly increased for risk factors, including number of fractures (OR, 2.65; 95% CI, 2.34-2.99), use of nonsteroidal anti-inflammatory drugs plus opioids (OR, 1.84; 95% CI, 1.73-1.95), operative treatment (OR, 1.78; 95% CI, 1.69-1.86), open fracture (OR, 1.66; 95% CI, 1.55-1.77), anticoagulant use (OR, 1.58; 95% CI, 1.51-1.66), osteoarthritis with rheumatoid arthritis (OR, 1.58; 95% CI, 1.38-1.82), anticonvulsant use with benzodiazepines (OR, 1.49; 95% CI, 1.36-1.62), opioid use (OR, 1.43; 95% CI, 1.34-1.52), diabetes (OR, 1.40; 95% CI, 1.21-1.61), high-energy injury (OR, 1.38; 95% CI, 1.27-1.49), anticonvulsant use (OR, 1.37; 95% CI, 1.31-1.43), osteoporosis (OR, 1.24; 95% CI, 1.14-1.34), male gender (OR, 1.21; 95% CI, 1.16-1.25), insulin use (OR, 1.21; 95% CI, 1.10-1.31), smoking (OR, 1.20; 95% CI, 1.14-1.26), benzodiazepine use (OR, 1.20; 95% CI, 1.10-1.31), obesity (OR, 1.19; 95% CI, 1.12-1.25), antibiotic use (OR, 1.17; 95% CI, 1.13-1.21), osteoporosis medication use (OR, 1.17; 95% CI, 1.08-1.26), vitamin D deficiency (OR, 1.14; 95% CI, 1.05-1.22), diuretic use (OR, 1.13; 95% CI, 1.07-1.18), and renal insufficiency (OR, 1.11; 95% CI, 1.04-1.17) (multivariate P < .001 for all). CONCLUSIONS AND RELEVANCE: The probability of fracture nonunion can be based on patient-specific risk factors at presentation. Risk of nonunion is a function of fracture severity, fracture location, disease comorbidity, and medication use.
27655499 Effects of 10-hydroxycamptothecin on differentiation of RAW264.7 cells into osteoclasts. 2016 Jul This study was designed to investigate the effect of 10-hydroxycamptothecin (10-HCPT) on osteoclast formation. RAW264.7 cells were cultured in vitro with 100 ng/ml receptor activator for nuclear factor-κ B ligand (RANKL) and 30 ng/ml recombinant macrophage colony stimulating factor (M-CSF), and 10-HCPT with different solubilities were added. After five-day cultivation, tartrate-resistant acid phosphatase (TRAP) staining was used to observe the number of osteoclasts. mRNA expression of osteoclast-specific genes, such as TRAP, cathepsin K (CTSK) and matrix metalloproteinase protease 9 (MMP-9), was detected by real-time Polymerase Chain Reaction (PCR). The effect of 10-HCPT on the proliferation activity of RAW264.7 cells was detected using Cell Counting Kit-8 (CCK-8). CCK-8 detection showed that 10-HCPT with a certain concentration (1 ng/ml to 5 ng/ml) had no effect on cell proliferation (P>0.05); 10-HCPT could inhibit the generation of osteoclasts. With the increase of the concentration of 10-HCPT, the number of osteoclasts generated from cells cultured with 10-HCPT [1 ng/ml (86±11.14), 2 ng/ml (66.67±7.51), 5ng/ml (27.67±6.51)] was much lower than that of the control group (145±8.19), and the difference was statistically significant (all P=0, P less than 0.05); mRNA expression of osteoclast-specific gene TRAP [1 ng/ml (24.38±0.68), 2 ng/ml (20.09±1.86), 5 ng/ml (6.23±0.53)], CTSK [1 ng/ml (10.08±0.81), 2 ng/ml (7.30±0.30), 5 ng/ml (3.20±0.56)] and MMP-9 [1 ng/ml (43.54±6.96), 2 ng/ml (28.28±5.83), 5 ng/ml (11.07±2.53)] was much lower than that of the groups added with RANKL and M-CSF only (all P=0, P less than 0.05), and with the increase of concentration of 10-HCPT, the expression of osteoclast-specific genes showed a decreasing tendency. All the findings suggest that 10-HCPT can inhibit the formation of osteoclasts by reducing the expression of osteoclast-specific genes such as TRAP, CTSK and MMP-9.
25108668 Ocular toxicity and functional vision recovery in a patient treated with hydroxychloroquin 2015 May We report the case of a 64-year-old woman with rheumatoid arthritis and Sjögren's syndrome, treated during 48 months with hydroxychloroquine that was removed after an ophthalmological evaluation showed bilateral vision loss associated with paracentral scotoma in the visual field, fundoscopic macular pigmentary changes, and severely impaired central multifocal electrorretinogram (mfERG). Twelve months after treatment withdrawal, visual acuity and central mfERG had surprisingly improved. This is an unusual case of functional recovery after treatment withdrawal. We consider that central mfERG is a more sensitive test than pattern electrorretinogram in the detection of retinal toxicity and functional vision recovery after hydroxychloroquine treatment cessation.
27188286 Long non-coding RNA expression profile in minor salivary gland of primary Sjögren's syndr 2016 May 17 BACKGROUND: To examine the roles of long noncoding RNAs (lncRNAs) in the regulation of primary Sjögren's syndrome (pSS) and reveal the expression profile of lncRNAs in labial salivary glands (LSGs) in pSS patients. METHOD: The expression of 63,431 lncRNAs and 39,887 mRNAs were determined in the LSG of four pSS patients and four healthy controls using microarray experiments. Validation was performed in 30 pSS patients and 16 controls using real-time PCR. LncRNA-mRNA co-expression and gene-pathway networks were constructed using bioinformatics software. RESULT: A total of 1243 lncRNAs (upregulated: 890, downregulated: 353) and 1457 mRNAs (upregulated: 1141, downregulated: 316) were differentially expressed in the LSGs of pSS patients (fold change >2, P <0.05). Eight of these lncRNAs were validated using real-time PCR. ENST00000420219.1 (3.13-fold), ENST00000455309.1 (2.51-fold), n336161 (2.45-fold), NR_002712 (2.41-fold), ENST00000546086.1 (1.94-fold), Lnc-UTS2D-1:1 (1.79-fold), n340599 (1.69-fold), and TCONS_l2_00014794 (1.28-fold) were significantly upregulated in pSS. There were strong correlations between these lncRNAs and β2 microglobulin, disease course, erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), IgA, IgM, visual analogue scale (VAS) of parotid swelling and VAS of dry eyes. Computational analyses revealed that 28 of the differentially expressed (DE) mRNAs were associated with eight DE lncRNAs involved in chemokine signaling pathways, the nuclear factor-kappa B (NF-κB) signaling pathway, and tumor necrosis factor (TNF) signaling pathway. CONCLUSIONS: Our study revealed the expression profile of lncRNAs in LSGs of pSS patients. Many novel lncRNA transcripts that play important roles in the pathogenesis of pSS were dysregulated in pSS. Therefore, this study will aid in the development of new diagnostic biomarkers and drug therapies.
26429306 Contribution of dendritic cell immunoreceptor (DCIR) polymorphisms in susceptibility of sy 2015 Nov Dendritic cell immunoreceptor (DCIR) has previously shown an association with rheumatoid arthritis (RA) in Caucasians and Han Chinese. This study was aimed to further investigate whether DCIR polymorphisms are novel susceptibility factors for other autoimmune diseases, i.e. systemic lupus erythematosus (SLE) and primary Sjogren's syndrome (SS). A total of 1502 patients with SLE, 476 patients with primary SS, and 1278 non-related healthy controls were enrolled in the study. The single-nucleotide polymorphisms (SNPs) rs2377422 and rs10840759 were genotyped using TaqMan assay. The differences in allelic and genotypic distribution between two groups were assessed using Pearson chi-square test, and logistic regression adjusting for age and sex, respectively. P-value < 0.025 was considered statistically significant by Bonferroni correction. The SNP rs2377422 confers an increased susceptibility risk to both SLE (allele model: P = 7.65 × 10(-4), OR 1.20; genotype recessive model: P = 0.012, OR 1.29), and primary SS (allele model: P = 3.74 × 10(-4), OR 1.31; genotype dominant model: P = 1.62 × 10(-4), OR 2.02). There is no association between rs10840759 and SLE or primary SS. In conclusion, DCIR SNP rs2377422 is a novel genetic susceptibility factor for both SLE and primary SS.
26867144 Association of Anticentromere Antibodies With More Severe Exocrine Glandular Dysfunction i 2016 Oct OBJECTIVE: Anticentromere antibodies (ACAs) define a subset of primary Sjögren's syndrome (SS) with a unique phenotype, including features of limited cutaneous systemic sclerosis and a lower frequency of anti-SSA/SSB antibodies. We sought to determine whether ACAs are associated with more severe exocrine glandular dysfunction in a large cohort of primary SS subjects. METHODS: We performed a cross-sectional analysis of 1,361 subjects with primary SS from the Sjögren's International Collaborative Clinical Alliance Registry, stratified by the presence or absence of ACAs. ACAs were assayed by immunofluorescence staining on HEp-2 cells. RESULTS: ACAs were present in 82 of the 1,361 SS subjects (6%) and were associated with older age, female sex, and lower frequencies of anti-SSA/SSB, rheumatoid factor, and hyperglobulinemia. Among ACA-positive versus ACA-negative subjects, there was a higher frequency of a focus score ≥2 (71% versus 53%; P = 0.002), a higher median focus score (2.8 versus 2.5; P = 0.0440), and greater exocrine gland dysfunction: Schirmer's test value: median 4 versus 5 mm/5 minutes; P = 0.0003, and unstimulated whole saliva (UWS) flow rate: median 0.08 versus 0.37 ml/5 minutes; P < 0.0001. ACA-positive subjects had an increased risk of UWS <0.1 ml/minute (odds ratio [OR] 12.24 [95% confidence interval (95% CI) 4.91-41.02]) and Schirmer's test value <5 mm/5 minutes (OR 2.52 [95% CI 1.50-4.36]) after correcting for age, sex, anti-SSA/SSB, and focus score. Labial gland fibrosis was not different between the 2 groups. CONCLUSION: In a large international registry of SS, ACA had an independent association with more severe exocrine glandular dysfunction. This dysfunction was associated with more pronounced labial salivary glandular inflammation but not fibrosis.
25861884 Diagnostic utility of Acoustic Radiation Force Impulse (ARFI) imaging in primary Sjoegren` 2015 Oct OBJECTIVES: The purpose of the study was to assess the diagnostic utility of acoustic radiation force impulse (ARFI) imaging in primary Sjögren's syndrome (pSS). METHODS: One hundred fifty-seven patients with sicca symptoms and/or salivary gland swelling were included. Sicca symptoms, Schirmer test, unstimulated whole saliva (UWS), SS-A/B antibodies, and histology were assessed according to American-European Consensus group (AECG) criteria. All patients underwent high-resolution ultrasound and ARFI imaging of the parotid (PG) and submandibular glands (SMG). RESULTS: Seventy patients were classified as having pSS. The remaining 87 patients suffered from idiopathic sicca (n = 24), rheumatoid arthritis (n = 12), sarcoidosis (n = 9), cutaneous/systemic lupus erythematosus (n = 7), scleroderma (n = 2), dermatomyositis (n = 1), HBV/HCV (n = 2), and panarteritis nodosa (n = 1), and disorders in 29 patients were classified as not otherwise specified. ARFI values of the PG were significantly higher in the pSS versus non-pSS groups (2.86 ± 0.07 m/s vs. 2.15 ± 0.11 m/s, p < 0.0001). ARFI imaging demonstrated diagnostic sensitivity and specificity of 81 % and 67 %, respectively. CONCLUSIONS: In addition to histology, ARFI imaging was the most important diagnostic tool for identifying early pSS. KEY POINTS: • Early stages in Sjögren's syndrome become apparent with major salivary gland enlargements. • Schirmer and unstimulated whole saliva tests demonstrated insufficient sensitivity/specificity for early-stage diagnosis. • Acoustic radiation force impulse imaging is a reliable tool for diagnosing early disease stages.
28031844 Refractory rheumatoid vasculitis. 2016 Nov Systemic rheumatoid vasculitis (SRV) can develop in rheumatoid arthritis of long duration and high disease activity. It most commonly manifests as cutaneous vasculitis and mononeuritis multiplex. This can involve any organ of the body and carries very high mortality. We report a case of a young male who had rheumatoid arthritis for the past 15 years and became refractory to standard drugs and anti-TNF agents. He subsequently developed SRV, which started as mononeuritis multiplex. Disease progressed to result in gangrene of hands and feet despite receiving intravenous cyclophosphamide. Intravenous immunoglobulin and rituximab also could not provide any response. Prolonged ICU stay resulted in critical care neuromyopathy. Central nervous system vasculitis developed even after repeated infusions of intravenous immunoglobulins and at last he died of complications. In this case report, we have presented rare and chronic protracted presentation of rheumatoid vasculitis involving skin, nerves, brain and testis, which was refractory to the recommended therapies.