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ID PMID Title PublicationDate abstract
26203828 Efficacy and Safety of Rituximab in Systemic Lupus Erythematosus and Sjögren Syndrome Pat 2015 Aug OBJECTIVE: Recent studies suggested a potential of rituximab (RTX) in treating autoimmune thrombocytopenia (AITP) secondary to autoimmune diseases. In this study, we retrospectively evaluated the efficacy and safety of RTX therapy in patients with refractory AITP secondary to systemic lupus erythematosus (SLE) and Sjögren syndrome (SS). METHODS: Twenty-one SLE and/or SS patients with treatment-resistant AITP were treated once or repeatedly with RTX at the Rheumatology Clinic Renji Hospital, during the period March 2012 to June 2014. Clinical and laboratory variables recorded at every follow-up visit were analyzed. RESULTS: The median age of all patients was 37.05 ± 3.15 years (range, 13-67 years; 20 female and 1 male). The median AITP duration before RTX treatment was 5.46 years. Previous treatments of 21 patients included immunosuppressive agents such as corticosteroids (n = 19), cyclosporine (n = 9), mycophenolate mofetil (n = 2), methotrexate (n = 3), cyclophosphamide (n = 2), vincristine (n = 3), and hydroxychloroquine (n = 15), and 7 patients received concomitantly intravenous immunoglobulin therapy. Two patients had undergone splenectomy without improvement. Seventeen patients (80.95%) were treated repeatedly with RTX during the follow-up period. The overall response rate to RTX treatment (including complete response, 52.38%; partial response, 28.57%) was 80.95%. A significant increase (P < 0.05) of platelet counts was seen after 1 month (median, 32.24 × 10/mL vs 66.53 × 10/mL). Relapses occurred mostly during the first 9 months, and maintaining duration of response was 10.27 months (range, 2-17 months) on average after the first RTX infusion. Antiplatelet antibodies, especially IgG isotype, decreased significantly (P < 0.05) after RTX treatment. No adverse effects were observed among 15 patients (71.4%); however, 2 cases died of severe pneumonia, and another developed lymphoma. CONCLUSIONS: Rituximab is an additional potent therapeutic treatment option for SLE and SS patients with AITP refractory to conventional immunosuppressive treatments. For most patients, RTX was safe and well tolerated.
27191226 Pregnancy and primary Sjögren's syndrome: management and outcomes in a multicentre retros 2017 Jan OBJECTIVES: Primary Sjögren's syndrome (pSS) is one of the most common autoimmune diseases, mainly affecting women during the fourth decade of life. During pregnancy, the presence of anti-Ro/SSa and anti-La/SSb antibodies increases the risk of congenital heart block (CHB). Foetal and pregnancy outcomes in pregnant women with pSS compared with the general population are difficult to evaluate because of confounding factors including age and body mass index (BMI). METHOD: The aim of this case-control study was to analyse the impact of pSS in pregnant women on foetal and pregnancy outcomes. RESULTS: We enrolled 19 women with pSS (54 pregnancies) matched by age and BMI to 216 controls. Patients with pSS delivered significantly earlier (38 weeks + 3 days vs. 39 weeks + 2 days) and experienced more spontaneous abortions [< 22 weeks of gestation (WG)] than the controls [n = 16/54 (30.0%) vs. n = 1/216 (0.4%); p < 0.00001]. Preterm delivery (≤ 37(+6) WG) was significantly higher in the pSS group than in the control group (29% vs. 12%, p = 0.04). pSS activity significantly affected the birthweight percentile, which was lower in pregnancies occurring after the diagnosis of pSS than in those occurring before (32.43 ± 21.57 vs. 60.46 ± 27.37; p = 0.008). No case of CHB was observed. CONCLUSIONS: pSS is responsible for an increased risk of spontaneous abortion. The duration of pregnancy is lower in patients with than without pSS, with more premature deliveries. Pregnancies that occur after the onset of the disease result in lower birthweight percentile children than when pSS is not clinically overt.
27181234 [Salivary epidermal growth factor (EGF) in Sjögren's syndrome: association between saliva 2016 Sjögren's syndrome (SS) is a chronic inflammatory autoimmune disease characterized by lymphocytic infiltration of the exocrine glands, especially the salivary and lacrimal glands. As a result of salivary gland dysfunction, most patients with SS have xerostomia, related to a reduced salivary flow rate. In addition to the discomfort due to xerostomia, dry mouth can cause various intraoral manifestations such as refractory stomatitis, ulcer and atrophic changes in the oral mucosa and tongue, and patients' quality of life (QOL) is impaired severely. These manifestations are believed to be caused mainly by a decrease in the clearance in the oral cavity owing to hyposalivation. However, since saliva has several beneficial physiological effects on the intraoral environment, qualitative changes in sialochemistry should also be considered a cause of the refractory intraoral manifestations in SS. Salivary epidermal growth factor (EGF) is considered an important cytoprotective factor against injuries, and it contributes to wound healing in the oral cavity. We evaluated changes in salivary EGF levels and assessed the association between salivary EGF levels and the severity of intraoral manifestations in SS patients. The results showed that the salivary EGF levels decreased with the progression of SS, and this deterioration in saliva quality as well as hyposalivation could play a role in the pathogenesis of refractory intraoral manifestations in SS patients. Our findings provide new target for therapeutic intervention in SS.
27041168 Thymic Extranodal Marginal Zone Lymphoma of Mucosa-associated Lymphoid Tissue with 8q24 Ab 2016 Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) of the thymus is reported to have characteristic features that distinguish it from MALT lymphoma of other organs; it is proposed to be a distinct clinicopathological subgroup of MALT lymphoma. We herein present a case of thymic MALT lymphoma accompanied by Sjögren's syndrome, involving the first report of a thymic MALT lymphoma patient carrying a chromosomal abnormality of 8q24. No c-myc gene translocation or c-Myc protein overexpression was observed, suggesting that c-myc was not involved in lymphomagenesis or progression. Although we did not examine the mechanisms by which the lymphoma developed, this chromosomal structural change in 8q24 may be associated with the pathogenesis in our case.
27634688 Lymphoepithelial infiltrate of palatal minor salivary glands: implications for diagnostic 2016 Dec Benign lymphoepithelial lesions (BLLs) usually affect the parotid glands, resulting in their asymmetrical enlargement. The condition can be associated with Sjögren's syndrome (SS), which in turn may predispose the affected patient to the development of malignant lymphoma. BLLs arising in the intraoral minor salivary glands are rare; such a lesion should prompt the work-up for SS. In some instances, a BLL of a minor salivary gland could represent the initial stage of a mucosa-associated lymphoid tissue (MALT) lymphoma. A case of BLL arising in the palatal minor salivary glands is reported here. The importance of an appropriate diagnostic work-up is emphasized and the relationship of BLL with SS is reinforced.
26959680 Arterial Spin Labeling Imaging for the Parotid Glands of Patients with Sjögren's Syndrome 2016 Sjögren's syndrome (SS) is characterized by hypofunction of the salivary and lacrimal glands. The salivary function is largely dependent upon the blood supply in the glands. However, the diseased states of the gland perfusion are not well understood. The arterial spin labeling (ASL) technique allows noninvasive quantitative assessment of tissue perfusion without the need for contrast agent. Here, we prospectively compared the perfusion properties of the parotid glands between patients with SS and those with healthy glands using ASL MR imaging. We analyzed salivary blood flow (SBF) kinetics of 22 healthy parotid glands from 11 volunteers and 28 parotid glands from 14 SS patients using 3T pseudo-continuous ASL imaging. SBF was determined in resting state (base SBF) and at 3 sequential segments after gustatory stimulation. SBF kinetic profiles were characterized by base SBF level, increment ratio at the SBF peak, and the differences in segments where the peak appeared (SBF types). Base SBFs of the SS glands were significantly higher than those of healthy glands (59.2 ± 22.8 vs. 46.3 ± 9.0 mL/min/100 g, p = 0.01). SBF kinetic profiles of the SS glands also exhibited significantly later SBF peaks (p < 0.001) and higher SBF increment ratios (74 ± 49% vs. 47 ± 39%, p = 0.04) than the healthy glands. The best SBF criterion (= 51.2 mL/min/100 mg) differentiated between control subjects and SS patients with 71% sensitivity and 82% specificity. Taken together, these results showed that the SS parotid glands were mostly hyperemic and the SS gland responses to gustatory stimulation were stronger and more prolonged than those of the healthy glands. The ASL may be a promising technique for assessing the diseased salivary gland vascularization of SS patients.
25278501 Increased rheumatoid factor and deep venous thrombosis: 2 cohort studies of 54628 individu 2015 Feb BACKGROUND: The risk of deep venous thrombosis is increased in patients with rheumatoid arthritis. We tested the hypothesis that increased concentrations of rheumatoid factor are associated with increased risk of deep venous thrombosis in individuals without autoimmune rheumatic disease in the general population. METHODS: We included 54628 participants from the Copenhagen City Heart Study (1981-83) and the Copenhagen General Population Study (2004-12), all with a measured concentration of IgM rheumatoid factor and without autoimmune rheumatic disease or venous thromboembolism. The main outcome was incident deep venous thrombosis. There were no losses to follow-up. RESULTS: During 368381 person-years, 670 individuals developed deep venous thrombosis. A rheumatoid factor concentration ≥ vs <110 IU/mL showed the strongest association with deep venous thrombosis, with multivariable adjusted hazard ratios of 9.0 (95% CI 3.1-26) for 1-year follow-up, 4.3 (2.2-8.5) for 5-year follow-up, and 3.1 (1.7-5.6) for up to 32 years of follow-up. Compared with rheumatoid factor concentrations <15 IU/mL, the multivariable adjusted hazard ratios for deep venous thrombosis during maximum follow-up were 1.3 (1.0-1.5) for 15-29 IU/mL, 1.7 (1.0-2.8) for 30-59 IU/mL, 2.4 (1.3-4.3) for 60-119 IU/mL, and 3.0 (1.6-5.6) for ≥120 IU/mL (trend P = 6 × 10(-7)). Results were similar in the 2 studies separately. Obese men and women age >60 years with rheumatoid factor concentrations ≥120 IU/mL had 10% and 8% 5-year risk of deep venous thrombosis. CONCLUSIONS: Increased rheumatoid factor in the general population was associated with up to 3-fold increased long-term risk and up to 9-fold increased 1-year risk of deep venous thrombosis.
26831786 [Screening for Potential Drug Targets by Comprehensive Identification of Disease-specific 2016 Our immune system resembles an intelligent security system, which continually monitors for foreign invaders (infectious diseases); however, in some cases, this system recognizes healthy parts as something harmful or foreign and then attacks them (autoimmune diseases). The defining characteristics of an autoimmune disease are the existence of T- and B-cell autoreactivity against self proteins (autoantigens). In addition to autoimmune diseases, aberrant host proteins that occur during a certain state of diseases (e.g., cancer) can be recognized as an autoantigen. Immune complexes (ICs) are produced during an immune response and may reflect some aspects of an ongoing immune response. Therefore, the identity of antigens incorporated into ICs provides the information that in the future may aid in the development of diagnosis and treatment strategies for autoimmune diseases, infection, cancer, and transplantation therapy, and this information might be more relevant than information on free antigens. We developed a novel proteomic strategy (immune complexome analysis) in which ICs are separated from serum, followed by direct tryptic digestion and nano-liquid chromatography-tandem mass spectrometry for the identification and profiling of antigens in circulating ICs. We applied this strategy to the analysis of circulating ICs in autoimmune diseases (rheumatoid arthritis, anti-neutrophil cytoplasmic antibody-associated vasculitis, Takayasu's arteritis, mixed connective tissue disease, dermatomyositis, Sjögren's syndrome, systemic scleroderma, and systemic lupus erythematosus), infectious diseases and cancers. In this review, we mainly discuss the results for autoimmune diseases.
30487857 Temperament traits, social support, and trauma symptoms among HIV/AIDS and chronic pain pa 2016 May The main goal of our study was to investigate and compare the relationship between temperament traits postulated by the Regulative Theory of Temperament (RTT) and social support dimensions with the level of trauma symptoms, as appear in posttraumatic stress disorder (PTSD), in an HIV/AIDS patient sample [HIV+ (n=182) and AIDS (n=128)] and in patients suffering from chronic pain (rheumatoid arthritis; n=150). The level of trauma symptoms was assessed with the PTSD Factorial Version Inventory (PTSD-F), temperament was measured with the Formal Characteristics of Behaviour-Temperament Inventory (FCB-TI), and social support was tested with the Berlin Social Support Scales (BSSS). Significant predictors of trauma symptoms among participants were temperament traits (emotional reactivity, perseveration, and sensory sensitivity), and social support dimensions (perceived support, need for support, support seeking, and actually received support). We also noticed significant differences between the levels of trauma symptoms, temperament, and social support between HIV/AIDS and chronic pain patients. The importance of trauma symptoms, as well as temperament traits and social support, should be taken into account in planning the forms of psychological support that should accompany pharmacotherapy for HIV/AIDS and chronic pain patients.
26016979 Intralymphatic histiocytosis overlying hip implantation treated with pentoxifilline. 2015 Jan Intralymphatic histiocytosis (IH) is a rare condition that presents with livedoid, erythematous to violaceous patches and plaques near affected joints most commonly in patients with rheumatoid arthritis and in at least 8 reports overlying metal implants. We report the case of a 58 year-old Caucasian woman who developed an indurated violaceous reticulated plaque overlying her right hip after placement of a metal hip implant 6 years prior for treatment of osteoarthritis. Histopathology revealed a proliferation of D2-40-positive dilated lymphatic spaces in the dermis and intralymphatic proliferation of CD68-positive histiocytes. Lab results included negative serology for rheumatoid factor and negative leukocyte function testing for metal allergies. The patient was treated with pentoxifylline, which resulted in decreased induration and erythema of the lesion with almost complete resolution of the plaque. This case highlights the diagnostic and therapeutic challenges of cutaneous reactive angiomatoses, which are rare skin conditions that can present with similar clinical and histologic findings and can be differentiated on the basis of immunostains that highlight vascular and lymphatic endothelium and histiocytes. Pentoxifylline may be considered as a therapeutic option because of its anti-inflammatory and antiplatelet activity.
27456855 Prevalence and predictors of hand involvement in Thai patients with systemic sclerosis. 2018 Jan AIM: Data regarding the clinical and radiographic hand involvement in Asian patients with systemic sclerosis (SSc) are limited. Thus, we determined the prevalence of clinical and radiographic hand involvement in Thai SSc patients, comparing diffuse cutaneous SSc (dcSSc) and limited cutaneous SSc (lcSSc). We also determined the factors associated with arthritis, contracture of fingers and digital ulcers. METHOD: SSc patients seen at the Rheumatology Clinic, Chiang Mai University, Thailand, from December 2012 to June 2013 were consecutively invited to enroll in the study. After study entry, demographic data, clinical features and hand radiographs were evaluated. RESULT: We studied 110 SSc patients (73 dcSSc) with mean ± SD age of 53.2 ± 9.2 years and disease duration from non-Raynaud's phenomenon of 4.9 ± 4.8 years. The prevalence of arthritis, finger contractures and digital ulcers were 10 (9.1%), 47 (42.7%), and 14 (12.7%), respectively. DcSSc patients had significantly more of the following hand complications than lcSSc patients: digital pitting scar (53.4% vs. 27.0%, P = 0.008), digital ulcer (17.8% vs. 2.7%, P = 0.032), traumatic ulcer (27.4% vs. 0%, P < 0.001), acrolysis (45.2% vs. 18.9%, P = 0.007) and flexion contracture (60.3% vs. 8.1%, P < 0.001). Radiographic finger contractures were more prevalent in the dcSSc subset. In multivariate logistic regression analysis, a positive rheumatoid factor was associated with arthritis; dcSSc, arthritis and modified Rodnan skin score (MRSS) > 18 were associated with contracture of fingers. Furthermore, hand MRSS > 4 was associated with digital ulcers. CONCLUSION: Our results confirm that dcSSc patients had more severe clinical hand complications than lcSSc. However, radiographic findings were similar among subgroups, except that more finger contractures were seen in dcSSc. Finally, the presence of rheumatoid factor is associated with arthritis, and high MRSS is associated with finger contractures and digital ulcers.
25793994 Lithothamnion muelleri treatment ameliorates inflammatory and hypernociceptive responses i 2015 Rheumatoid Arthritis (RA) is a chronic disease characterized by persistent inflammation and pain. Alternative therapies to reduce these symptoms are needed. Marine algae are valuable sources of diverse bioactive compounds. Lithothamnion muelleri (Hapalidiaceae) is a marine algae with anti-inflammatory, antitumor, and immunomodulatory properties. Here, we investigated the potential anti-inflammatory and analgesic activities of L. muelleri in a murine model of antigen-induced arthritis (AIA) in mice. Our results demonstrate that treatment with L. muelleri prevented inflammation and hypernociception in arthritic mice. Mechanistically, the crude extract and the polysaccharide-rich fractions of L. muelleri may act impairing the production of the chemokines CXCL1 and CXCL2, and consequently inhibit neutrophil influx to the knee joint by dampening the adhesion step of leukocyte recruitment in the knee microvessels. Altogether our results suggest that treatment with L.muelleri has a potential therapeutic application in arthritis treatment.
26209517 Trabecular bone loss in collagen antibody-induced arthritis. 2015 Jul 25 INTRODUCTION: Postmenopausal women with rheumatoid arthritis (RA) have increased risk of developing osteoporosis due to chronic inflammation and estrogen deprivation. Collagen antibody-induced arthritis (CAIA), an experimental polyarthritis model representing the effector phase of arthritis, is mainly mediated by the innate immune system. Compared to the widely used collagen-induced arthritis model, CAIA is conveniently short and can be used in C57BL/6 mice, enabling studies with knock-out mice. However, the impact on bone of the CAIA model in C57BL/6 mice has not previously been studied. Therefore, the aim of this study was to determine if CAIA can be used to study postmenopausal arthritis-induced osteoporosis. METHODS: CAIA was induced by administration of collagen-type II antibodies and lipopolysaccharide to ovariectomized female C57BL/6J mice. Control mice received lipopolysaccharide, but no antibodies. Nine days later, femurs were collected for high-resolution micro-CT and histomorphometry. Serum was used to assess cartilage breakdown and levels of complement. Frequencies of immune cell subsets from bone marrow and lymph nodes were analyzed by flow cytometery. RESULTS: Trabecular bone mass was decreased and associated with increased number of osteoclasts per bone surface in the CAIA model. Also, the frequency of interleukin-17(+) cells in lymph nodes was increased in CAIA. CONCLUSION: The present study show that CAIA, a short reproducible arthritis model that is compatible with C57BL/6 mice, is associated with increased number of osteoclasts and trabecular bone loss.
25889670 Kinetics of gene expression and bone remodelling in the clinical phase of collagen-induced 2015 Mar 5 INTRODUCTION: Pathological bone changes differ considerably between inflammatory arthritic diseases and most studies have focused on bone erosion. Collagen-induced arthritis (CIA) is a model for rheumatoid arthritis, which, in addition to bone erosion, demonstrates bone formation at the time of clinical manifestations. The objective of this study was to use this model to characterise the histological and molecular changes in bone remodelling, and relate these to the clinical disease development. METHODS: A histological and gene expression profiling time-course study on bone remodelling in CIA was linked to onset of clinical symptoms. Global gene expression was studied with a gene chip array system. RESULTS: The main histopathological changes in bone structure and inflammation occurred during the first two weeks following the onset of clinical symptoms in the joint. Hereafter, the inflammation declined and remodelling of formed bone dominated. Global gene expression profiling showed simultaneous upregulation of genes related to bone changes and inflammation in week 0 to 2 after onset of clinical disease. Furthermore, we observed time-dependent expression of genes involved in early and late osteoblast differentiation and function, which mirrored the histopathological bone changes. The differentially expressed genes belong to the bone morphogenetic pathway (BMP) and, in addition, include the osteoblast markers integrin-binding sialoprotein (Ibsp), bone gamma-carboxyglutamate protein (Bglap1), and secreted phosphoprotein 1 (Spp1). Pregnancy-associated protein A (Pappa) and periostin (Postn), differentially expressed in the early disease phase, are proposed to participate in bone formation, and we suggest that they play a role in early bone formation in the CIA model. Comparison to human genome-wide association studies (GWAS) revealed differential expression of several genes associated with human arthritis. CONCLUSIONS: In the CIA model, bone formation in the joint starts shortly after onset of clinical symptoms, which results in bony fusion within one to two weeks. This makes it a candidate model for investigating the relationship between inflammation and bone formation in inflammatory arthritis.
27809921 Effects by periodontitis on pristane-induced arthritis in rats. 2016 Nov 3 BACKGROUND: An infection-immune association of periodontal disease with rheumatoid arthritis has been suggested. This study aimed to investigate the effect of pre-existing periodontitis on the development and the immune/inflammatory response of pristane-induced arthritis. METHODS: We investigated the effect of periodontitis induced by ligature placement and Porphyromonas gingivalis (P. gingivalis) infection, in combination with Fusobacterium nucleatum to promote its colonization, on the development of pristane-induced arthritis (PIA) in rats (Dark Agouti). Disease progression and severity of periodontitis and arthritis was monitored using clinical assessment, micro-computed tomography (micro-CT)/intraoral radiographs, antibody response, the inflammatory markers such as α-1-acid glycoprotein (α-1-AGP) and c-reactive protein (CRP) as well as cytokine multiplex profiling at different time intervals after induction. RESULTS: Experimentally induced periodontitis manifested clinically (P < 0.05) prior to pristane injection and progressed steadily until the end of experiments (15 weeks), as compared to the non-ligated arthritis group. Injection of pristane 8 weeks after periodontitis-induction led to severe arthritis in all rats demonstrating that the severity of arthritis was not affected by the pre-existence of periodontitis. Endpoint analysis showed that 89% of the periodontitis-affected animals were positive for antibodies against arginine gingipain B and furthermore, the plasma antibody levels to a citrullinated P. gingivalis peptidylarginine deiminase (PPAD) peptide (denoted CPP3) were significantly (P < 0.05) higher in periodontitis rats with PIA. Additionally, there was a trend towards increased pro-inflammatory and anti-inflammatory cytokine levels, and increased α-1-AGP levels in plasma from periodontitis-challenged PIA rats. CONCLUSIONS: Pre-existence of periodontitis induced antibodies against citrullinated peptide derived from PPAD in rats with PIA. However, there were no differences in the development or severity of PIA between periodontitis challenged and periodontitis free rats.
26622511 Phenotypic characterization of type II collagen-induced arthritis in Wistar rats. 2015 Oct The aim of the present study was to determine a more specific, efficient and simple method for the induction of collagen-induced arthritis (CIA) in rats. Different strains of rats were injected at the base of the tail with bovine type II collagen (CII) emulsified in incomplete Freund's adjuvant (IFA). The onset and severity of arthritis were evaluated by clinical assessment. The established CIA model was analyzed using a comprehensive examination of clinical, hematological, histological and radiological parameters. The results demonstrated that Wistar rats were the most susceptible strain to CIA followed by Wistar Furth rats, with Sprague Dawley rats being the least susceptible. Following primary and booster immunization, female Wistar rats developed severe arthritis, with an incidence of >83% and low variability in clinical signs. The development of arthritis was accompanied by a significantly elevated erythrocyte sedimentation rate compared with that in the control rats. The radiographic examination revealed bone matrix resorption, considerable soft tissue swelling, periosteal new bone formation and bone erosion in the arthritic joints of the CIA rats. Histopathologically, the synovial joints of CIA rats were characterized by synovial hyperplasia, pannus formation, marked cellular infiltration, bone and cartilage erosion and narrowing of the joint space. The administration of an intradermal injection of only 200 µg bovine CII emulsified in IFA at the base of the tail therefore leads to the successful development of a CIA rat model. This well-characterized CIA rat model could be specifically used to study the pathophysiology of human rheumatoid arthritis as well as to test and develop anti-arthritic agents for humans.
28007558 Aryl hydrocarbon receptor suppresses the osteogenesis of mesenchymal stem cells in collage 2017 Jan 15 The contributions of aryl hydrocarbon receptor (Ahr) to the pathogenesis of rheumatoid arthritis (RA), particularly bone loss, have not been clearly explored. The imbalance between osteoblasts and osteoclasts is a major reason for bone loss. The dysfunction of osteoblasts, which are derived from mesenchymal stem cells (MSCs), induced bone erosion occurs earlier and is characterized as more insidious. Here, we showed that the nuclear expression and translocation of Ahr were both significantly increased in MSCs from collagen-induced arthritis (CIA) mice. The enhanced Ahr suppressed the mRNA levels of osteoblastic markers including Alkaline phosphatase (Alp) and Runt-related transcription factor 2 (Runx2) in the differentiation of MSCs to osteoblasts in CIA. The 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD)-mediated activation of Ahr dose-dependently suppressed the expression of osteoblastic markers. In addition, the expression of β-catenin was reduced in CIA MSCs compared with control, and the TCDD-mediated activation of the Ahr significantly inhibited β-catenin expression. The Wnt3a-induced the activation of Wnt/β-catenin pathway partly rescued the osteogenesis decline induced by TCDD. Taken together, these results indicate that activated Ahr plays a negative role in CIA MSCs osteogenesis, possibly by suppressing the expression of β-catenin.
27059799 The Efficacy and Safety of Clazakizumab, an Anti-Interleukin-6 Monoclonal Antibody, in a P 2016 Sep OBJECTIVE: To evaluate the efficacy of clazakizumab, a monoclonal antibody with high affinity and specificity for the interleukin-6 (IL-6) cytokine, in psoriatic arthritis (PsA). METHODS: In this randomized, double-blind, placebo-controlled, dose-ranging study (ClinicalTrials. gov identifier: NCT01490450), patients with active PsA and an inadequate response to nonsteroidal antiinflammatory drugs were randomized (1:1:1:1) to receive subcutaneous placebo or clazakizumab 25 mg, 100 mg, or 200 mg every 4 weeks, with or without methotrexate. The primary end point was the response rate according to the American College of Rheumatology 20% criteria for improvement (ACR20) at week 16, with secondary efficacy end points at weeks 16 and 24. RESULTS: A total of 165 patients were randomized. At week 16, the ACR20 response rate was significantly higher with clazakizumab 100 mg versus placebo (52.4% versus 29.3%; P = 0.039). ACR20 response rates at week 16 were 46.3% with clazakizumab 25 mg (P = 0.101 versus placebo) and 39.0% with clazakizumab 200 mg (P = 0.178 versus placebo). ACR50/ACR70 response rates were numerically higher with clazakizumab versus placebo at weeks 16 and 24. Compared with placebo, clazakizumab treatment significantly improved musculoskeletal manifestations (joint signs and symptoms, enthesitis, and dactylitis), with minimal improvements in skin disease, without clear evidence of a dose response. Clazakizumab was well tolerated. CONCLUSION: This is the first clinical trial of an IL-6-targeted therapy in PsA. Clazakizumab may be an effective treatment option for musculoskeletal aspects of PsA, but because of the lack of a dose response in this study, further studies are required to confirm the appropriate dose. The safety profile is consistent with the pharmacology of IL-6 blockade and prior clinical experience with this antibody in rheumatoid arthritis.
26166501 Chikungunya Fever in Japan Imported from the Caribbean Islands. 2016 A 53-year-old Japanese woman who was working as a volunteer in the Commonwealth of Dominica in the Caribbean islands presented with a high-grade fever and severe incapacitating generalized arthralgia. The Asian genotype of the chikungunya virus was confirmed using reverse transcription-PCR and serology, based on the presence of a specific neutralization titer and immunoglobulin M antibodies. She was diagnosed with post-chikungunya chronic arthritis based on persistence of her polyarthritis for 3 months and the presence of rheumatoid factor, immunoglobulin G-rheumatoid factor, and matrix metalloproteinase-3. Chikungunya virus should be considered as a causative pathogen in travelers returning from Caribbean islands. Clinicians should consider chikungunya fever in the differential diagnosis of patients who complain of chronic arthritis and have a history of travel to an endemic area.
26900394 Health status of male steel workers at an electric arc furnace (EAF) in Trentino, Italy. 2016 BACKGROUND: The aim of this retrospective cohort study was to determine if the workers of an Electric Arc Furnace (EAF), which recycles scrap, had higher mortality and morbidity due to possible exposure to pollutants at work. EAFs do not run on coke ovens. In EAFs 40 % of the particulate matter (PM) is made up of PM 2.5. The foundry dust contained iron, aluminum, zinc, manganese, lead, chromium, nickel, cadmium, mercury, arsenic, polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls and dioxins. METHODS: Mortality study: a cohort of 331 exposed workers (6731 person-years) was studied from 19/03/1979 to 31/12/2009 (mean follow up 20.7 years). The group of exposed workers was compared to the general population and to a small control group of 32 workers from the same company. Morbidity study: rates of exemption from health fee for the seven major diseases of 235 exposed workers were compared to the rates of exemption in the Province of Trento. RESULTS: Mortality study: an excess mortality was found in the exposed workers as compared to the general population (SMR 1.13; 95 % CI: 0.76-1.62; 29 deaths) and to the internal group (RR 2.34; 95 % CI: 0.39-95.7). The mortality rate was increased for all tumours (SMR 1.36; 95 % CI: 0.75-2.29; 14 cases), for lung cancer (SMR 3.35; 95 % CI 1.45-6.60; 8 cases), for ischemic heart disease (SMR 1.27; 95 % CI: 0.35-3.26; 4 cases), for chronic liver disease (SMR 1.16; 95 % CI: 0.14-4.20; 2 cases) and for injury and poisoning (SMR 1.32; 95 % CI: 0.48-2.88; 6 cases). Morbidity study: there was a statistically significant increase of diabetes, rheumatoid arthritis, hypertension and cardiovascular diseases in exposed workers. CONCLUSIONS: With the limitations of this relatively small cohort, we found a statistically significant increase of diabetes, cardiovascular diseases and deaths due to lung cancer in exposed workers. These findings cannot be explained by PAH exposure alone; metal particulates are the most important pollutants in the working area of EAFs. A reliable method for measuring metal PM in tissues is urgently needed for exposure assessment. This study underlines the necessity to maximize the standards of security toward foundry dusts/diffuse emission. Further studies on EAF's are needed to confirm our findings and to increase statistical power.