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ID PMID Title PublicationDate abstract
23320392 Targeting IL-1 in Sjögren's syndrome. 2013 Apr INTRODUCTION: IL-1 plays key roles in the biological functions of various cells. In particular, many roles of IL-1 in the immune system have been discovered by numerous studies. This review focuses on the association of IL-1 with the pathogenesis of autoimmunity. AREAS COVERED: An overview of the biological functions of the IL-1 family and the IL-1 receptors (IL-1Rs), including the maintenance of systemic or local homeostasis, and the signaling pathway through IL-1/IL-1R in various immune systems are described. Several functions of IL-1 in the pathogenesis of Sjögren's syndrome (SS) have been demonstrated with a focus on the immune responses and target tissues in SS. In addition to the role of IL-1 in the immune responses in SS, the function of IL-1 in ocular mucosa lesions in SS has been described. Lastly, there is an overview of possible therapeutic strategies for IL-1 inhibition in SS. EXPERT OPINION: IL-1 plays critical roles in the onset and development of SS by controlling systemic or local immune responses and maintaining the survival and mucosal defense of target epithelial cells. The inhibition of the pathogenic functions of IL-1 may be beneficial for treating SS.
23312448 Mesenchymal stromal cells isolated from children with systemic juvenile idiopathic arthrit 2013 Mar BACKGROUND AIMS: Infusion of mesenchymal stromal cells (MSCs) has been reported to be an effective treatment modality for acute graft-versus-host disease, and MSCs have been considered for use in the treatment of patients with autoimmune diseases. Before contemplating clinical studies with MSCs in patients with systemic juvenile idiopathic arthritis (sJIA), the immunomodulatory capacity of MSCs in this setting needs to be explored. A comparative analysis of bone marrow-derived MSCs from children with sJIA and healthy pediatric controls was performed. METHODS: MSCs were successfully expanded from 11 patients with sJIA and 10 controls. The phenotype, differentiation and immunomodulatory capacity of these MSCs were compared. The effect of immunosuppressive drugs on MSC function was also investigated. RESULTS: MSCs from patients with sJIA and controls showed no differences in their suppressive effect using control peripheral blood mononuclear cells. Furthermore, the suppression of the response of peripheral blood mononuclear cells from patients with sJIA by autologous sJIA MSCs and allogeneic control MSCs was comparable. The immunosuppressive effect of both groups of MSCs was diminished in the presence of indomethacin (P < 0.05). MSCs from patients with sJIA and controls suppressed interleukin-2-induced natural killer cell activation to a similar extent. In addition, MSCs of patients with sJIA and controls inhibited the differentiation of monocytes to dendritic cells. CONCLUSIONS: This is the first explorative study in a significant cohort of patients with sJIA to evaluate the effect of MSCs on adaptive and innate immune responses. The comparable immunosuppressive characteristics of MSCs derived from patients with sJIA to age-matched controls support the potential use of patient-derived MSCs in the treatment of sJIA.
23892265 A rapamycin-binding protein polymer nanoparticle shows potent therapeutic activity in supp 2013 Nov 10 Sjögren's syndrome (SjS) is a chronic autoimmune disease characterized initially by lymphocytic infiltration and destruction of exocrine glands, followed by systemic organ damage and B-cell lymphoma. Conventional treatment is based on management of symptoms and there is a shortage of therapies that address the underlying causes of inflammation at source exocrine tissue. The aim of this study was to test a novel protein polymer-based platform consisting of diblock copolymers composed from Elastin-like Polypeptides (ELPs) fused with FKBP12, to deliver a potent immunosuppressant with dose-limiting toxicity, rapamycin (Rapa) also known as Sirolimus, and evaluate its effects on the inflamed lacrimal gland (LG) of non-obese diabetic mouse (NOD), a classic mouse model of SjS. Both soluble and diblock copolymer ELPs were fused to FKBP12 and characterized with respect to purity, hydrodynamic radii, drug entrapment and release. Both formulations showed successful association with Rapa; however, the nanoparticle formulation, FSI, released drug with nearly a 5 fold longer terminal half-life of 62.5h. The strong interaction of FSI nanoparticles with Rapa was confirmed in vivo by a shift in the monoexponential pharmacokinetic profile for free drug to a biexponential profile for the nanoparticle formulation. When acutely administered by injection into NOD mice via the tail vein, this FSI formulation significantly suppressed lymphocytic infiltration in the LG relative to the control group while reducing toxicity. There was also a significant effect on inflammatory and mammalian target of Rapamycin (mTOR) pathway genes in the LG and surprisingly, our nanoparticle formulation was significantly better at decreasing a proposed tear biomarker of SjS, cathepsin S (CATS) compared to free drug. These findings suggest that FSI is a promising tool for delivering Rapa for treatment of SjS in a murine model and may be further explored to meet the unmet medical challenge of SjS.
23301790 Sjögren's syndrome-like autoimmune sialadenitis in MRL-Faslpr mice is associated with exp 2013 Jun Although costimulatory molecules have been shown to play crucial roles in the immune response, their involvement in the pathogenesis of Sjögren's syndrome is incompletely understood. In this study, we evaluated the relationship between the severity of spontaneous Sjögren's syndrome-like autoimmune sialadenitis in MRL/MpJ-lpr/lpr (MRL-Fas(lpr)) mice and the expression of 6 costimulatory molecules that play important roles in the immune response: CD80, CD86, OX40 ligand (OX40L), 4-1BB ligand (4-1BBL), glucocorticoid-induced TNF receptor-related protein ligand (GITRL), and B cell-activating factor of the tumor necrosis factor family (BAFF). Expression of the costimulatory molecules in the submandibular salivary glands of age-matched autoimmune MRL-Fas(lpr) mice and non-autoimmune MRL/MpJ-+/+(MRL/+) and C3H/HeJ-lpr/lpr (C3H-Fas(lpr)) mice was examined immunohistochemically and scored on a scale of 0 to 3. The severity of sialadenitis was evaluated histologically and scored on a scale of 0 to 3. We found that all of the costimulatory molecules were expressed in duct epithelial cells of salivary glands from MRL-Fas(lpr) mice, whereas immunoreactivity was absent or weak in the MRL/+ mice. The staining intensity for all 6 costimulatory molecules was significantly higher in the MRL-Fas(lpr) than in the MRL/+ mice. Partial correlation analysis was performed to assess the degree of association between costimulatory molecule staining scores and disease scores, which clearly revealed a significant correlation for only GITRL and 4-1BBL. These molecules showed negligible immunoreactivity in the submandibular glands of C3H-Fas(lpr) mice, suggesting that their expression was independent of the Fas(lpr) mutation. In conclusion, the expression of GITRL and 4-1BBL in salivary gland duct epithelial cells is associated with background genes in the MRL strain, but not with the Fas(lpr) mutation itself, and contributes significantly to the pathogenesis of autoimmune sialadenitis in MRL-Fas(lpr) mice. These results suggest that GITRL and 4-1BBL may be effective targets for the development of therapies for Sjögren's syndrome.
23628400 Meta-analysis reveals an association of STAT4 polymorphisms with systemic autoimmune disor 2013 Aug Signal transducer and activator of transcription 4 (STAT4) has been recently identified as a susceptibility gene for multiple autoimmune diseases. Here we performed a comprehensive analysis of the association between STAT4 and several different autoimmune disorders to identify potential common inflammatory principles behind this association. Our meta-analysis revealed that the STAT4 rs7574865 polymorphism is associated with four autoimmune diseases with systemic pathology, including systemic lupus erythematosus (OR = 1.52; 95% CI = 1.48 - 1.56, P<1.0 × 10(-16)), rheumatoid arthritis (OR = 1.27; 95% CI = 1.21 - 1.33, P < 1.00 × 10(-16)), systemic sclerosis (OR = 1.38; 95% CI = 1.27 - 1.50, P < 1.44 × 10(-14)), and primary Sjogren's syndrome (OR = 1.32; 95% CI = 1.01 - 1.73, P = 4.40 × 10(-2)), while no association was found with type I diabetes, juvenile idiopathic arthritis, ulcerative colitis and Crohn's disease. Furthermore, the stratified meta-analysis also demonstrate that the STAT4 rs7574865 polymorphism is associated with the presence of autoantibodies with systemic reactivity (anti-ds-DNA antibodies) in SLE patients (OR = 1.37; 95% CI = 1.21 - 1.56, P = 1.12 × 10(-6)). However, no such specific association was seen in RA with regard to the presence of non-systemically reacting antibodies, including rheumatoid factor and anti-cyclic citrullinated peptide antibodies. Taken together, these results suggest that STAT4 polymorphisms are associated with autoimmune diseases which are characterized by a systemic pathology and anti-dsDNA antibody.
23345026 Novel mechanisms of action of the biologicals in rheumatic diseases. 2014 Aug Biological drugs targeting pro-inflammatory or co-stimulatory molecules or depleting lymphocyte subsets made a revolution in rheumatoid arthritis (RA) treatment. Their comparable efficacy in clinical trials raised the point of the heterogeneity of RA pathogenesis, suggesting that we are dealing with a syndrome rather than with a single disease. Several tumor necrosis factor-alpha (TNF-α) blockers are available, and a burning question is whether they are biosimilar or not. The evidence of diverse biological effects in vitro is in line with the fact that a lack of efficacy to one TNF-α agent does not imply a non-response to another one. As proteins, biologicals are potentially immunogenic. It has been recently raised that anti-drug antibodies (ADA) may affect their bioavailability and eventually the clinical efficacy through local formation of immune complexes and directly by preventing the interaction between the drug and TNF-α. Regular monitoring of drug and ADA levels appears the best way to tailor anti-TNF-α therapies. Owing to the pleiotropic characteristics of the target, anti-TNF-α blockers may affect several mechanisms beyond rheumatoid synovitis. As TNF-α plays a pivotal role in the induction of early atherosclerosis, treatment with TNF-inhibitors may modulate cholesterol handling, in particular, cholesterol efflux from macrophages. Side effects are a major issue because of the systemic TNF-α blocking action. The efficacy of an anti-C5 monoclonal antibody fused to a peptide targeting inflamed synovia in experimental arthritis opened the way for new strategies: Homing to the synovium of molecules neutralizing TNF would allow to maximize the therapeutic action avoiding the side effects.
23464885 Achilles enthesis ultrasound: the importance of the bursa in spondyloarthritis. 2013 May OBJECTIVES: This paper aims to assess the prevalence and relevance of the bursa-synovial lesion in spondyloarthritis (SpA). METHODS: A transversal blind and controlled two-dimensional (2D) and three-dimensional (3D) ultrasound (US) study of Achilles enthesis bursa in early SpA was undertaken. Clinical outcome measures were collected. RESULTS: Bilateral Achilles enthesis of 66 early SpA patients (34 women) and 46 control patients (23 asymptomatic healthy subjects and 23 rheumatoid arthritis [RA] patients) were analysed. Mean BASDAI, BASFI and BASRI-spine were 4.55±2.08, 2.16±1.95 and 0.65±0.77, respectively. Mean erythrocyte sedimentation rate (ESR) was 10.93±12.35 mm/h and C-reactive protein (CRP) was 6.46±10.09 mg/l. The κ-values for intra-reader agreement for 2D and 3D images and bursa measurement were 0.82 and 0.98, respectively. Bursas were visualised in 89/132 SpA enthesis (67.4%) vs. 27/46 enthesis (58.7%) of healthy controls (p<0.01), and 10/46 enthesis (21.7%) of RA controls (p<0.01). When the thicknesses of the bursas were analysed, the SpA group had a mean of 1.52±1.47 mm versus 0.76±0.76 mm in the healthy control group (p<0.0001), and 0.38±0.62 mm in the RA control group (p<0.0001). A positive likelihood ratio of 4.6 with a cut-off point of bursa >2 was found. No Doppler signal was detected in controls, but 6.6% of SpA Achilles enthesis had Doppler bursitis. Heel pain was more frequent when bursa was present (p<0.05). When Doppler was present, male predominance, HLA B27 positive, heel pain, and higher number of swollen joints, CRP levels, disease activity by the patient and BASDAI questions 2 and 3 achieved statistical significance (p<0.01). CONCLUSIONS: The presence of bursa and Doppler signal at retrocalcaneal bursa level could have a relevant contribution to differentiate SpA patients, and were correlated with clinical outcomes of SpA disease activity.
25476210 [Clinical analysis of 24 cases of bisphosphonate-related osteonecrosis of the jaw]. 2014 Sep OBJECTIVE: To retrospectively analyze the data of the patients with Bisphosphonate-related osteonecrosis of the jaw over the past five years in our hospital. METHODS: Twenty-four patients with bisphosphonate-related osteonecrosis of the jaw treated in our hospital from 2009 to 2013 were included. The medication, bisphosphonate types, clinical signs and symptom, treatment methods and results were also analyzed. RESULTS: Of the 24 cases, 20 cases suffered from malignant tumors and received intravenous infusion of bisphosphonates and 4 cases took oral bisphosphonates. Three of the 4 cases with osteoporosis had history of glucocorticoid (rheumatoid arthritis). All patients had oral clinical symptoms for an average of 11.6 months, and 19 patients had the history of tooth extraction. There were 11 cases with mandible involved, 10 cases with maxilla involved, and 3 cases with both mandible and maxilla involved. After conservative treatment (3 cases) or operation (21 cases), 10 cases had wound healing, 6 cases were stable with bone exposure, and 4 cases with died bone needed reoperation. During the follow-up period, there was one patient died of primary disease (renal carcinoma). CONCLUSIONS: Both intravenous and oral application routes of bisphosphonates can induce osteonecrosis of the jaw. Bisphosphonate-related osteonecrosis of the jaw can be caused by alveolar trauma. The treatment modality is to relieve the clinical symptoms of bisphosphonate-related osteonecrosis of the jaw.
25606590 Clinical value of whole-body PET/CT in patients with active rheumatic diseases. 2014 Advanced imaging techniques may enable early diagnosis and monitoring of therapy in various rheumatic diseases. To prevent irreversible tissue damage, inflammatory rheumatic disease must be diagnosed and treated in pre-clinical stages, requiring highly sensitive detection techniques. Positron emission tomography (PET) provides highly sensitive, quantitative imaging at a molecular level, revealing the important pathophysiological processes underlying inflammation. This review provides an overview of the current utility of 18 F-fluorodeoxyglucose (FDG)-PET/computed tomography (CT) in patients with active rheumatic diseases such as rheumatoid arthritis, spondyloarthritis, polymyalgia rheumatica, adult-onset Still's disease, relapsing polychondritis, immunoglobulin G4-related disease, large-vessel vasculitis, Wegener's granulomatosis, polymyositis, and dermatomyositis. We also discuss the role of FDG-PET/CT in the diagnosis and monitoring of these diseases.
25789374 Use of next-generation DNA sequencing to analyze genetic variants in rheumatic disease. 2014 Next-generation DNA sequencing has revolutionized the field of genetics and genomics, providing researchers with the tools to efficiently identify novel rare and low frequency risk variants, which was not practical with previously available methodologies. These methods allow for the sequence capture of a specific locus or small genetic region all the way up to the entire six billion base pairs of the diploid human genome. Rheumatic diseases are a huge burden on the US population, affecting more than 46 million Americans. Those afflicted suffer from one or more of the more than 100 diseases characterized by inflammation and loss of function, mainly of the joints, tendons, ligaments, bones, and muscles. While genetics studies of many of these diseases (for example, systemic lupus erythematosus, rheumatoid arthritis, and inflammatory bowel disease) have had major successes in defining their genetic architecture, causal alleles and rare variants have still been elusive. This review describes the current high-throughput DNA sequencing methodologies commercially available and their application to rheumatic diseases in both case–control as well as family-based studies.
25519036 [Osteosynthesis of talonavicular fusion with a claw plate and compression screw]. 2015 Jun OBJECTIVE: A new method of osteosynthetic stabilization of talonavicular fusion is presented. INDICATIONS: Idiopathic and posttraumatic talonavicular arthritis, talonavicular destruction in rheumatoid arthritis, adult acquired flatfoot deformity, cavovarus deformity, talonavicular degenerative disease in tarsal coalition. CONTRAINDICATION: Major hindfoot deformity or instability, severe osteopenic conditions of tarsal bones. SURGICAL TECHNIQUE: Talonavicular fusion is stabilized with a medioplantar 6.5-mm lag screw in combination with a dorsolateral 3.5-mm claw plate (Charlotte Claw compression plate; Fa. Wright Medical Technology, Memphis, USA) by a dorsal surgical access. POSTOPERATIVE MANAGEMENT: Nonweight-bearing in a cast or walker for 6 weeks; after radiologic control increasing weight-bearing is allowed. RESULTS: The technique was used in 44 patients, among them 31 cases of isolated talonavicular fusion. Complete bony healing was observed in 42 cases after medium follow-up time of 13.3 months. All 19 cases of isolated talonavicular fusion without posterior tibial tendon dysfunction healed uneventfully; two cases of non-union were observed in 12 patients with posterior tibial tendon dysfunction.
24461235 Primary shoulder reverse arthroplasty: surgical technique. 2014 Feb Total reverse shoulder replacement is now a very common surgical procedure that has been shown to be effective in the treatment of rotator cuff tear arthropathies or massive rotator cuff tears with pseudo paralysis, even without arthritis. However, the survival curves of the oldest series decrease between 8 and 10 years after arthroplasty (events: implant survival, or worsening of clinical outcome) which explains why the indication for this type of arthroplasty is usually limited to patients over seventy. Moreover, details and technical modifications have been suggested to improve the surgical technique, the quality of fixation and the mechanical conditions of this non-anatomical prosthesis to improve clinical outcome and implant survival. Within the framework of primary surgery, excluding traumatic or revision surgery, the primary indications for this option are massive rotator cuff tears with (or without) osteoarthritis and primary osteoarthritis with rotator cuff tears and/or with severe glenoid wear and finally, rheumatoid arthritis. The purpose of this conference was to assess and describe the most important preoperative criteria and surgical conditions necessary for this procedure as well as specific technical details about the surgical procedure itself based on available options and options under evaluation such as the positioning of the glenoid component (lateralization, bone graft, orientation) and the association of muscle transfers.
24445386 Early-onset sarcoidosis caused by a rare CARD15/NOD2 de novo mutation and responsive to in 2015 Feb Granulomatous autoinflammatory diseases are monogenic syndromes caused by mutations in the region encoding for the nucleotide-binding domain region of the NOD2/CARD15 gene with subsequent dysregulation of the inflammatory response and formation of noncaseous granulomas. They include Blau syndrome (BS) and early-onset sarcoidosis (EOS); both are clinically and genetically indistinguishable between them and they are the familial (autosomal dominantly inherited) and sporadic forms of the same disease, respectively. We describe a case of EOS, misdiagnosed for 30 years such as "juvenile rheumatoid arthritis" before and "classic sarcoidosis" later. In our patient, we found a new de novo mutation (E383G) in NOD2 that has been reported only in a family of Japanese patients with BS. After long-term follow-up (42 months), infliximab maintained good efficacy and safety without any sign of disease relapse and side effects.
24184141 From the Medical Board of the National Psoriasis Foundation: The risk of cardiovascular di 2014 Jan BACKGROUND: Many studies have identified cardiovascular risk factors in patients with psoriasis. Some psoriasis therapies may increase cardiovascular disease (CVD) and others may decrease CVD. OBJECTIVE: We reviewed the literature to define the impact of common psoriasis therapies on cardiovascular measures and outcomes. RESULTS: Phototherapy has no major cardiovascular impact and may reduce levels of proinflammatory cytokines. Acitretin increases serum lipids and triglycerides, but has not been shown to increase cardiovascular risk. Cyclosporine A increases blood pressure, serum triglycerides, and total cholesterol. Methotrexate is associated with a decreased risk of CVD morbidity and mortality. Among the biologics, data for tumor necrosis factor inhibitors suggest an overall reduction in cardiovascular events. Most data on short-term ustekinumab use suggest no effect on major adverse cardiovascular events, however some authorities remain concerned. Nevertheless, ustekinumab use over a 4-year period shows a decrease in major adverse cardiovascular events when compared both with the general US population and with psoriatics in Great Britain. LIMITATIONS: Most studies lack the power and randomization of large clinical trials and long-term follow-up periods. In addition, the increased risk of CVD associated with psoriasis itself is a confounding factor. CONCLUSION: Some therapies for moderate to severe psoriasis, including methotrexate and tumor necrosis factor inhibitors, may reduce cardiovascular events in psoriatic patients. Ustekinumab appears to be neutral but there may be a long-term benefit. Appropriate patient counseling and selection and clinical follow-up are necessary to maximize safety with these agents. Further long-term study is necessary to quantify the benefits and risks associated with biologic therapies.
24364201 [Hip arthroscopy]. 2013 Sep In the last ten years, hip arthroscopy has been developing intensively and it is rapidly gaining primacy in the treatment of various injuries and damages to the hip itself and its immediate vicinity. The basic advantage of hip arthroscopy surgery versus classic open surgery is avoiding an open dislocation of the hip and, thus, reducing patient's morbidity and accelerating his/her rehabilitation, which leads to a quicker return to everyday activities. The success of arthroscopic surgery depends on the correct indication for the surgery and on the experience and the skill of the operator. It also depends on the properly conducted rehabilitation and the patient's compliance, as well as on the patient's realistic expectations. Indications for hip arthroscopy today are the following: injury and damage to acetabular labrum and/or articular cartilage, femoroacetabular impingement syndrome, injuries and damages to the ligament of the femoral head, loose and foreign joint bodies as well as different conditions of synovial membrane (synovial chondromatosis, pigmented villonodular synovitis and other inflammatory arthropathy such as rheumatoid arthritis). In this article we describe the indications, technique, complications and the prospect of hip arthroscopy, with a detailed overview of contemporary literature data.
24231066 Epigenetics and methylation in the rheumatic diseases. 2014 Apr OBJECTIVES: Rheumatic diseases encompass a wide range of conditions of poorly characterized etiopathology, many having both genetic and environmental susceptibility factors. Epigenetic studies are providing new insights into disease pathogenesis. Recent rheumatology literature related to DNA methylation studies-both epigenome-wide and candidate gene-are discussed, as well as methodological issues. METHOD: A PubMed search for articles published until April 2013 was conducted using the following keywords: ("methylation" OR "epigenetics") AND ("rheumatoid arthritis" OR "lupus" OR "autoimmune disease" OR "osteoporosis" OR "osteoarthritis" OR "musculoskeletal disorder") and EWAS. The reference lists of identified articles were searched for further articles. RESULTS: Several genome-wide methylation studies have been reported recently, mostly in autoimmune rheumatic diseases. Overall, these studies have identified methylation signatures in disease, clustering of subgroups as well as new and known epigenetic associations. Methodological issues, small sample sizes and reduced coverage of methylation assays render many results preliminary. CONCLUSIONS: There have been a number of epigenetic advances in rheumatic diseases recently. The new technologies and emerging field of epigenome-wide association will provide novel perspectives in disease etiology, diagnosis, classification, and therapy.
21801113 Leflunomide: dermatologic perspective. 2013 Apr Leflunomide, an isoxazole derivative, is a disease-modifying antirheumatic drug. It has successfully been used for the treatment of rheumatoid arthritis as a feasible alternative to methotrexate. Recently, leflunomide has been used in certain dermatologic conditions. Medline/PubMed search revealed only 201 articles of its application in dermatologic conditions, of which 21 were relevant for inclusion. Prime mode of action of leflunomide is through the inhibition of dihydroorotate dehydrogenase, a key enzyme in the de novo pyrimidine synthesis pathway used by lymphocytes for clonal expansion. The current level of evidence and strength of recommendation suggest its use in psoriasis and psoriatic arthritis. However, the use of leflunomide in severe atopic dermatitis, systemic lupus erythematosus, Wegener's granulomatosis, primary Sjögren's syndrome, bullous pemphigoid, dermatomyositis, sarcoidosis and systemic sclerosis still requires further evaluation.
24091748 In vivo action of IL-27: reciprocal regulation of Th17 and Treg cells in collagen-induced 2013 Oct 4 Interleukin (IL)-27 is a novel cytokine of the IL-6/IL-12 family that has been reported to be involved in the pathogenesis of autoimmune diseases and has a pivotal role as both a pro- and anti-inflammatory cytokine. We investigated the in vivo effects of IL-27 on arthritis severity in a murine collagen-induced arthritis (CIA) model and its mechanism of action regarding control of regulatory T (Tregs) and IL-17-producing T helper 17 (Th17) cells. IL-27-Fc-treated CIA mice showed a lower severity of arthritis. IL-17 expression in the spleens was significantly decreased in IL-27-Fc-treated CIA mice compared with that in the CIA model. The Th17 population was decreased in the spleens of IL-27-Fc-treated CIA mice, whereas the CD4(+)CD25(+)Foxp3(+) Treg population increased. In vitro studies revealed that IL-27 inhibited IL-17 production in murine CD4(+) T cells, and the effect was associated with retinoic acid-related orphan receptor γT and signal transducer and activator of transcription 3 inhibition. In contrast, fluorescein isothiocyanate-labeled forkhead box P3 (Foxp3) and IL-10 were profoundly augmented by IL-27 treatment. Regarding the suppressive capacity of Treg cells, the proportions of CTLA-4(+) (cytotoxic T-lymphocyte antigen 4), PD-1(+) (programmed cell death protein 1) and GITR(+) (glucocorticoid-induced tumor necrosis factor receptor) Tregs increased in the spleens of IL-27-Fc-treated CIA mice. Furthermore, in vitro differentiated Treg cells with IL-27 exerted a more suppressive capacity on T-cell proliferation. We found that IL-27 acts as a reciprocal regulator of the Th17 and Treg populations in CD4(+) cells isolated from healthy human peripheral blood mononuclear cells (PBMCs), as well as from humans with rheumatoid arthritis (RA) PBMCs. Our study suggests that IL-27 has the potential to ameliorate overwhelming inflammation in patients with RA through a reciprocal regulation of Th17 and Treg cells.
24064287 Autoimmune diseases-related arthritis in HIV-infected patients in the era of highly active 2015 Apr BACKGROUND: Autoimmune diseases-related arthritis has been rarely reported in HIV-1-infected patients. We aimed to investigate the incidence and clinical manifestations of autoimmune diseases-related arthritis in HIV-infected patients in the era of highly active antiretroviral therapy (HAART) in Taiwan. METHODS: We retrospectively reviewed medical records of all HIV-infected patients who had a diagnosis of autoimmune arthritis between 1993 and 2013. Demographic characteristics, clinical manifestations, serial CD4 and CD8 lymphocyte counts and plasma HIV viral loads, HLA-B27 status, and treatment response to HIV and rheumatic diseases were recorded. RESULTS: During the 20-year study period, totally 26 HIV-infected patients with autoimmune arthritis (0.7%) were diagnosed among 3623 HIV-infected patients. There were 18 patients with ankylosing spondylitis (AS), six with rheumatoid arthritis (RA), one with psoriatic arthritis, and one with Sjögren's syndrome. HLA-B27 antigens were all detected positive of AS patients. Fifteen patients (57.7%) developed autoimmune arthritis after HAART was initiated. The median age and CD4(+) T lymphocyte counts at the diagnosis of autoimmune arthritis were 35 (20-62 years) and 406 (3-695 cells/μL), respectively. Three patients had typical presentations of Reiter's syndrome. Both AS and RA patients achieved a good virological response with undetectable plasma HIV RNA load 12 months after receiving HAART(85.71% vs. 80%, respectively, p = 0.999). The treatment response to antirheumatic medications were similar between AS patients and RA patients (77.8% vs. 50%, p = 0.3068), but seems to be better than that reported for the general population (30-40%). CONCLUSION: A low prevalence of autoimmune arthritis among HIV-infected patients in the era of HAART was similar to that of the general Taiwanese population. Clinical manifestations of HIV-infected patients were similar to those described in HIV-uninfected patients. However, the treatment response to antirheumatic agents was better in HIV-infected patients in our study.
24928921 Fenofibrate vs pioglitazone: Comparative study of the anti-arthritic potencies of PPAR-alp 2014 BACKGROUND: Rheumatoid arthritis is characterized by synovial hyperplasia, inflammatory infiltration, cartilage destruction and juxta-articular as well as generalized bone demineralization. Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily which behave as ligand-activated transcription factors in response to endogenous fatty acids and eicosanoids or isotype selective synthetic compounds as fibrates and thiazolidinediones. Beyond their key role in lipid metabolism, increased evidence has shown a role of the three isotypes in inflammatory modulation. We and others demonstrated previously that PPAR-gamma agonists reduced the severity of experimental polyarthritis and the overall inflammatory-induced bone loss. OBJECTIVE: To compare the anti-arthritic potencies of a PPAR-alpha agonist (fenofibrate, a lipid lowering drug) and a PPAR-gamma agonist (pioglitazone, formerly used as an antidiabetic drug) in rat adjuvant-induced arthritis. METHODS: Male Lewis rats were sensitized by an intra-dermal injection of 1 mg complete Freund's adjuvant at the basis of the tail and were treated orally for 21 days with fenofibrate 100 mg/kg/day (FENO) or pioglitazone 30 mg/kg/day (PIO), or with vehicle only. Arthritis severity was evaluated by clinical observations (oedema, clinical score, body weight). Global and femoral bone mineral density (BMD), femoral bone mineral content (BMC) were measured by dual-energy X-ray absorptiometry (DEXA) before sensitization and at day 20. Synovial mRNA levels of IL-1beta and IL-6 were determined by real-time RT-PCR. RESULTS: Administration of fenofibrate (100mg/kg/d) and pioglitazone (30 mg/kg/d) significantly reduced hindpaw oedema and arthritis score. Treatment with fenofibrate exerted a better effect on clinical scoring. DEXA analysis revealed that pioglitazone and fenofibrate treatment to a greater extent, reduced inflammatory-bone loss and increased BMD versus vehicle-treated rats. Finally, we demonstrated that both agonists decreased synovial expression of IL-1beta and IL-6. CONCLUSION: Pioglitazone and fenofibrate decreased arthritis severity in adjuvant-induced arthritis. Both agonists partially protected animals from inflammatory induced-bone loss.