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ID PMID Title PublicationDate abstract
25836642 Pulmonary manifestations of Sjögren syndrome, systemic lupus erythematosus, and mixed con 2015 May Interstitial lung disease is a common and often life-threatening manifestation of different connective tissue disorders, often affecting its overall prognosis. Systemic lupus erythematosus, Sjögren syndrome, and mixed connective tissue disease, although all unique diseases, can have lung manifestations as an important part of these conditions. This article reviews the different pulmonary manifestations seen in these 3 systemic rheumatologic conditions.
26237438 Challenges in the classification of fibrotic ILD: Patient case 2. 2015 Aug 3 PATIENT PRESENTATION AND DIAGNOSTIC WORK-UP: The patient is a 72-year-old man presenting with dyspnoea on exertion. He is a former heavy smoker (40 pack-years) and his father, now deceased, had rheumatoid arthritis (RA). On physical examination he had mild bi-basilar crackles but no finger clubbing. Autoimmune serology was positive for rheumatoid factor (RF: 25 IU/ml). Lung function tests showed normal FVC, a FEV1/FVC ratio of 72% and a TLCO of 49% predicted. Lung CT showed centrilobular and paraseptal emphysema, subpleural fine reticulation and traction bronchiolectasis, with no clear basal predominance (Figure 1). BAL cytology showed 83% alveolar macrophages, 12% lymphocytes, 3% neutrophils, and 2% eosinophils.
27562110 Primary Sjögren's Syndrome White Matter Changes and Cognitive Dysfunction. 2016 This case report describes a 52-year-old, female applicant for long term-care insurance with a history of an autoimmune connective tissue disease initially diagnosed as systemic lupus erythematosus (SLE). Over several years, the signs and symptoms evolved into a clear diagnosis of primary Sjögren's syndrome (PSS). The specific criteria for this diagnosis are reviewed including the symptoms, antinuclear antibodies (ANA), extractable nuclear antigen antibodies (ENA), abnormal salivary scintigraphy and positive Schirmer test. Symptoms of neuropathy and the possibility of a cognitive dysfunction are discussed as part of PSS. The association of white matter lesions (WML) with PSS is significant for underwriting consideration.
24899571 Identification of lymphoma predictors in patients with primary Sjögren's syndrome: a syst 2015 Jan To identify risk and predictors of lymphoma or lymphoproliferative disease in patients with primary Sjögren syndrome. Articles were identified through a comprehensive search strategy in Medline, Embase and Cochrane CENTRAL. Studies had to investigate primary Sjögren syndrome patients, 18 years of age or older, with the goal of examining potential clinical, immunological and hematological risk factors for lymphoma or lymphoproliferative disease. The quality of the studies was graded using the Oxford Levels of Evidence Scale. Whenever possible, the authors created evidence tables and performed meta-analysis. Of 900 studies identified, 18 were selected for inclusion. These studies provided data from over 15,000 patients (90 % female) for analysis. Lymphadenopathy, parotid enlargement, palpable purpura, low C4 serum levels and cryoglobulins were the most consistent non-Hodgkin´s lymphoma/lymphoproliferative disease predictors. Additionally, some of the studies identified splenomegaly, low C3 serum levels, lymphopenia and neutropenia as significant prognostic factors. The detection of germinal center-like lesions in primary Sjögren Syndrome diagnostic salivary biopsies was also proposed as highly predictive of non-Hodgkin´s lymphoma. In contrast, anemia, anti-Ro, anti-La, antinuclear antibodies, rheumatoid factor, male gender and hypergammaglobulinemia were not associated with lymphoma or lymphoproliferative disease. Patients with primary Sjögren syndrome have an increased risk of lymphoma or lymphoproliferative disease compared to the general population. Ascertaining relevant and reliable predictors in this patient population would greatly facilitate the identification of patients at elevated risk for closer monitoring in the context of limited resources.
27079168 β2-adrenoceptor signaling reduction in dendritic cells is involved in the inflammatory re 2016 Apr 15 Rheumatoid arthritis (RA) is characterized by inflammation of the synovium, which leads to the progressive destruction of cartilage and bone. Adrenoreceptor (AR) signaling may play an important role in modulating dendritic cell (DC), which may be involved in the pathogenesis of RA. We examined the effect of the β-AR agonist isoprenaline (ISO) on DC function, the impact of the β2-AR agonist salbutamol on adjuvant-induced arthritic (AA) rats, and changes in β2-AR signaling in DCs during the course of AA. ISO inhibited the expression of the surface molecules CD86 and MHC-II, inhibited the stimulation of T lymphocyte proliferation by DC and TNF-α secretion, and promoted DC antigen uptake and IL-10 secretion. The effects of ISO on MHC-II expression, DC stimulation of T lymphocyte proliferation, and DC antigen uptake were mediated by β2-AR. Treatment with salbutamol ameliorated the severity of AA and histopathology of the joints and inhibited proliferation of thymus lymphocytes and FLS in vivo. β2-AR signaling was weaker in AA rats compared to the control. Elevated GRK2 and decreased β2-AR expression in DC cytomembranes were observed in AA and may have decreased the anti-inflammatory effect of β2-AR signaling. Decreased β2-AR signaling may be relevant to the exacerbation of arthritis inflammation.
25617125 The antibody atliximab attenuates collagen-induced arthritis by neutralizing AIMP1, an inf 2015 Mar ARS-interacting multifunctional protein 1 (AIMP1) induces production of inflammatory cytokines from immune cells. Since osteoclastogenesis is promoted by positive regulation of inflammatory cytokines, whether AIMP1 could promote osteoclastogenesis was investigated. AIMP1 induced osteoclastogenesis and acted synergistically with RANKL to promote osteoclastogenesis. Down-regulation of CD23, an AIMP1 receptor, abolished AIMP1-mediated osteoclastogenesis. Enzyme-linked immunosorbent assays showed that the AIMP1 level was significantly higher in the peripheral blood (PB) and synovial fluid of rheumatoid arthritis patients than in normal PB. A monoclonal antibody (clone 15B3AF) that blocked the cytokine activity of AIMP1 inhibited the AIMP1-mediated production of inflammatory cytokines. Clone 15B3AF inhibited the AIMP1-mediated osteoclastogenesis in vitro. We then cloned the complementary determining regions of clone 15B3AF and generated a chimeric antibody (atliximab). In a collagen-induced arthritis mouse model (CIA), atliximab administration significantly attenuated disease severity and improved various histopathological parameters. Three-dimensional micro-computed tomography scanning confirmed that atliximab enhanced the joint structures in CIA mice. Furthermore, atliximab decreased the expression of inflammatory cytokines in the serum and inflamed joints of CIA mice. Taken together, our findings suggest that AIMP1 exacerbates RA by promoting inflammation and osteoclastogenesis and that atliximab could be developed as a therapeutic antibody to target inflammatory diseases, including RA.
27695067 Insulin-Like Growth Factor I Does Not Drive New Bone Formation in Experimental Arthritis. 2016 INTRODUCTION: Insulin like growth factor (IGF)-I can act on a variety of cells involved in cartilage and bone repair, yet IGF-I has not been studied extensively in the context of inflammatory arthritis. The objective of this study was to investigate whether IGF-I overexpression in the osteoblast lineage could lead to increased reparative or pathological bone formation in rheumatoid arthritis and/or spondyloarthritis respectively. METHODS: Mice overexpressing IGF-I in the osteoblast lineage (Ob-IGF-I+/-) line 324-7 were studied during collagen induced arthritis and in the DBA/1 aging model for ankylosing enthesitis. Mice were scored clinically and peripheral joints were analysed histologically for the presence of hypertrophic chondrocytes and osteocalcin positive osteoblasts. RESULTS: 90-100% of the mice developed CIA with no differences between the Ob-IGF-I+/- and non-transgenic littermates. Histological analysis revealed similar levels of hypertrophic chondrocytes and osteocalcin positive osteoblasts in the ankle joints. In the DBA/1 aging model for ankylosing enthesitis 60% of the mice in both groups had a clinical score 1<. Severity was similar between both groups. Histological analysis revealed the presence of hypertrophic chondrocytes and osteocalcin positive osteoblasts in the toes in equal levels. CONCLUSION: Overexpression of IGF-I in the osteoblast lineage does not contribute to an increase in repair of erosions or syndesmophyte formation in mouse models for destructive and remodeling arthritis.
25726968 TNF-alpha gene polymorphisms can help to predict response to etanercept in psoriatic patie 2015 Sep BACKGROUND: Genetic factors might have a role for lack of therapeutic response to anti-TNF-alpha agents, as previously suggested in patients with rheumatoid arthritis and inflammatory bowel disease. OBJECTIVES: We evaluated the role of the main TNF-alpha polymorphisms (-238G>A, -308G>A, -857C>T) in predicting the response to etanercept, an anti-TNF-alpha fusion protein. MATERIAL AND METHODS: Genomic DNA was extracted from buccal epithelial cells in a series of 97 psoriatic patients who received etanercept for at least 3 months. Patients were classified as responders, if they achieved a PASI improvement ≥ 75% after 12 weeks of etanercept treatment, and non-responders, if PASI improvement was <75%. Single-nucleotide polymorphisms (SNPs) in TNF-alpha gene (-238G>A, -308G>A, -857C>T) were genotyped by PCR restriction fragment length polymorphism (RFLP) assays. RESULTS: We found that patients heterozygous (GA) for the -238G>A polymorphism were more likely not responsive to therapy compared to the GG genotype. In fact, the GA genotype was found in 5/59 (8.5%) responders and in 14/38 (36.8%) non-responders (P = 0.001). A significant relationship with therapy was also observed for the -308G>A polymorphisms. In fact, the GG, GA and AA genotypes were detected in 48 (81.4%), 9 (15.3%) and 2 (3.4%) of the 59 responders and in 22 (57.9%), 11 (28.9%) and 5 (13.2%) of the 38 non-responder patients (P = 0.03). No association with therapy was observed for the -857C>T polymorphisms. CONCLUSION: Our study supports the role of TNF-alpha polymorphisms in predicting the response to anti-TNF-alpha agents. In particular, we found that the presence of -238G>A and -308G>A polymorphisms is associated with poor response to a 3-month therapy with etanercept. However, our data have yet to be validated in larger cohorts.
25269878 The association between susceptibility to inflammatory arthritis and miR-146a, miR-499 and 2015 Sep OBJECTIVE: The aim of this study was to explore whether polymorphisms in miR-146a, miR-499 and IRAK1 are associated with susceptibility to inflammatory arthritis. METHODS: Manual searches performed in the MEDLINE and EMBASE databases were used to identify published articles in which the roles of microRNA (miRNA) and IRAK1 polymorphisms in inflammatory arthritis were determined. A meta-analysis was conducted to investigate associations of the miR-146a rs2910164, miR-499 rs3746444, IRAK1 rs3027898 and IRAK1 rs1059703 polymorphisms with susceptibility to inflammatory arthritis. RESULTS: Nine studies containing 1224 patients and 1841 controls were included in the meta-analysis. The meta-analysis revealed no association between inflammatory arthritis and the rs2910164 C allele of miR-146a (odds ratio, OR = 0.974; 95 % confidence interval, CI = 0.810-1.091; p = 0.650). Stratification by ethnicity or disease type revealed no association between the miR-146a C allele and inflammatory arthritis in European, Middle Eastern or Asian patients with rheumatoid arthritis (RA) or juvenile idiopathic arthritis (JIA). However, the meta-analysis revealed an overall association between RA and the miR-499 rs374644 C (OR = 1.123, 95 % CI = 1.019-2.586, p = 0.041); stratification by ethnicity revealed a particular association in Middle Eastern populations (OR = 1.943, 95 % CI = 1.508-2.504, p = 2.7 × 10(-8)). The meta-analysis of IRAK1 polymorphisms revealed an association between inflammatory arthritis and the rs3027898 CC genotype (OR = 2.602, 95 % CI = 1.387-4.879, p = 0.003). An analysis using the homozygote contrast showed the same pattern for the rs3027898 CC genotype (OR = 2.472, 95 % CI = 1.300-4.700, p = 0.006). No association between inflammatory arthritis and the rs1059703 polymorphism was found. CONCLUSION: This meta-analysis suggests that the miR-499 rs374644 and IRAKI rs3027898 polymorphisms are associated with susceptibility to inflammatory arthritis.
26523062 New Approaches in Tumor Necrosis Factor Antagonism for the Treatment of Psoriatic Arthriti 2015 Nov The pathogenesis of psoriatic arthritis (PsA) is still under discussion but great advances have been made in the last 2 decades that confirm the central role of tumor necrosis factor-α (TNF-α) in its inflammatory milieu. New therapeutic approaches have been proposed, and new molecules with anti-TNF-α activity have been chemically altered to improve their pharmacological properties. Certolizumab pegol (CZP) is a PEGylated Fc-free anti-TNF that has been shown clinically to be effective in the treatment of rheumatoid arthritis (RA), skin psoriasis, and PsA. This article summarizes available data on its clinical efficacy and safety profile in the treatment of patients with PsA.
27802332 Anti-Arthritic Activity of Schistosoma mansoni and Trichinella spiralis Derived-Antigens i 2016 A growing body of evidence supports the concept of helminths therapy in a variety of autoimmune diseases. Here, we aimed to investigate the protective effects of autoclaved Schistosoma mansoni antigen (ASMA) and Trichinella spiralis antigen (ATSA) on the clinical and immunopathological features of rheumatoid arthritis (RA). Adjuvant arthritis was induced by subcutaneous and intradermal injections of complete Freund's adjuvant into the plantar surface of the right hind paw and the root of the tail, respectively. Rats were randomly assigned to serve as normal control, untreated arthritis, ASMA or ATSA-treated arthritis groups. Antigens were given by intradermal injection in two doses, two weeks apart. The development, progression of arthritic features, and the impact on animals' gait and body weight were followed up for 4 weeks. The associated changes in serum cytokines (IL-17, IFN-γ and IL-10), joints' histopathology and immunohistochemistry of Foxp3+ T regulatory cells (Tregs) were evaluated at the end of the study. Treatment with either ASMA or ATSA attenuated the progression of clinical features of polyarthritis, improved gait and body weight gain, reduced the elevated serum IL-17 and further increased both IFN-γ and IL-10. Histopathologically, this was associated with a remarkable regression of paws' inflammation that was limited only to the subcutaneous tissue, and a significant increase in the number of Foxp 3+ cells versus the untreated arthritis group. In conclusion, both Schistosoma mansoni and Trichinella spiralis derived antigens exerted protective effect against adjuvant arthritis with better effect achieved by ASMA treatment. This anti-arthritic activity is attributed to upregulation of the Foxp3+ Tregs, with subsequent favorable modulation of both pro- and anti-inflammatory cytokines. The use of autoclaved parasitic antigens excludes the deleterious effects of imposing helminthic infection by using live parasites, which may pave the way to a new therapeutic modality in treating RA.
26189022 Effect of galantamine on adjuvant-induced arthritis in rats. 2015 Oct 5 Stimulation of the vagus nerve suppresses cytokine production and macrophage activation, via the interaction of its neurotransmitter acetylcholine (ACh) with the α7 subunit of the nicotinic acetylcholine receptor (α7nAChR), present on neurons and inflammatory cells. The present study aimed to verify the potential anti-inflammatory effect of galantamine against experimental arthritis induced in rats. Fourteen days post adjuvant injection, Sprague-Dawley rats were treated orally with three doses of galantamine (1.25, 2.5 and 5 mg/kg) or leflunomide (10 mg/kg) for 2 weeks and arthritis progression was assessed by hind paw swelling. Additionally, serum biomarkers, viz., anti-cyclic citrullinated peptide antibodies (Anti-CCP), tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10) and monocyte chemoattractant protein-1 (MCP-1) were measured. Radiological examination of the hind paws was also carried out to evaluate the degree of joint damage. Adjuvant arthritis led to a significant weight loss, marked swelling of the hind paw and alteration in the serum levels of anti-CCP, TNF-α, IL-10 and MCP-1. These alterations were associated with significant radiological changes of the joints. Galantamine, in a dose-dependent manner, reduced significantly all biomarkers of inflammation, with the highest dose showing the best beneficial anti-inflammatory effect that was superior in magnitude to the reference drug leflunomide in most of the studied parameters. In conclusion, these results suggest that galantamine may represent a novel, inexpensive and effective therapeutic strategy in the treatment of rheumatoid arthritis.
26107746 Preventive Effect of a Novel Recombinant sTNFRII on Collagen-Induced Arthritis. 2015 We developed a novel trimeric sTNFRII fusion protein, named sTNFRII-gAD, which exhibited a higher in vitro antagonistic efficacy for TNFα in comparison with sTNFRII-Fc. This study aimed to investigate the arthritic protection of sTNFRII-gAD in a rat collagen-induced arthritis (CIA). The rats were injected intradermally with collagen type II at days 0 and 7. Three days after the second injection (day 10), the rats were intraperitoneally given sTNFRII-gAD or sTNFRII-Fc, or PBS. Effects of treatments were examined with respect of CIA incidence, severity and pathological changes. Serum TNFα, IL-17A and regulatory T cell (Treg) in periphery were determined at days 10 and 16, respectively. Our results showed that sTNFRIIgAD significantly reduced CIA incidence and severity (p < 0.05); meanwhile it led to a dramatic improvement in cartilage and bone damage. Moreover, the increase in serum anti-CII and IL-17A, and the reduction in Treg population were inhibited (p < 0.05) by sTNFRII-gAD or sTNFRII-Fc. Serum TNFα was found to be accumulated in the groups treated with sTNFRII-gAD or sTNFRII-Fc compared with the group treated with PBS (p < 0.05). It is noteworthy that sTNFRII-gAD displayed a better efficacy than sTNFRII-Fc in CIA incidence, pathological changes in cartilage and the elevation of anti-CII antibody, indicating that sTNFRII-gAD is potentially a more efficacious anti-TNFα agent for rheumatoid arthritis.
27444150 Expression of tyrosine hydroxylase in CD4(+) T cells contributes to alleviation of Th17/Tr 2016 Dec Tyrosine hydroxylase (TH), a rate-limiting enzyme for the synthesis of catecholamines, is expressed in T lymphocytes. However, the role of T cell-expressed TH in rheumatoid arthritis (RA) is less clear. Herein, we aimed to show the contribution of TH expression by CD4(+) T cells to alleviation of helper T (Th)17/regulatory T (Treg) imbalance in collagen-induced arthritis (CIA), a mouse model of RA. CIA was prepared by intradermal injection of collagen type II (CII) at tail base of DBA1/J mice. Expression of TH in the spleen and the ankle joints was measured by real-time polymerase chain reaction and Western blot analysis. Percentages of TH-expressing Th17 and Treg cells in splenic CD4(+) T cells were determined by flow cytometry. Overexpression and knockdown of TH gene in CD4(+) T cells were taken to evaluate effects of TH on Th17 and Treg cells in CIA. TH expression was upregulated in both the inflamed tissues (spleen and ankle joints) and the CD4(+) T cells of CIA mice. In splenic CD4(+) T cells, the cells expressing TH were increased during CIA. These cells that expressed more TH in CIA were mainly Th17 cells rather than Treg cells. TH gene overexpression in CD4(+) T cells from CIA mice reduced Th17 cell percentage as well as Th17-related transcription factor and cytokine expression and secretion, whereas TH gene knockdown enhanced the Th17 cell activity. In contrast, TH gene overexpression increased Treg-related cytokine expression and secretion in CD4(+) T cells of CIA mice, while TH gene knockdown decreased the Treg cell changes. Collectively, these findings show that CIA induces TH expression in CD4(+) T cells, particularly in Th17 cells, and suggest that the increased TH expression during CIA represents an anti-inflammatory mechanism.
26572759 Interleukin-35 upregulates OPG and inhibits RANKL in mice with collagen-induced arthritis 2016 Apr IL-35 is a novel anti-inflammatory cytokine, but the exact role of IL-35 in the progression of RA remains unclear, especially associated with osteoporosis and bone erosion. The present research has not been reported. Our purpose is to study how IL-35 affects RA bone destruction. INTRODUCTION: This study investigated the effect of interleukin-35 (IL-35) on OPG and RANKL expression in collagen-induced arthritis (CIA) in rats and in cultured fibroblast-like synoviocytes (FLS). METHODS: Thirty DBA/1J mice were randomly assigned to three groups (n = 10 per group): the control group, the CIA group, and the CIA + IL-35 group. Collagen-induced arthritis was induced by immunization with collagen. IL-35 was intraperitoneally injected daily for 10 days, starting from the 24(th) day after immunization. FLS cells were isolated and cultured from CIA. The expression of IL-17, RANKL, and OPG was determined by RT-PCR and Western blot. Each experiment was repeated three times. RESULTS: CIA mice exhibited arthritis symptoms on day 24, followed by a rapid progression of arthritis. The expression of IL-17 and RANKL was increased and the expression of OPG was decreased in CIA mice compared with control mice. IL-35 treatment inhibited the development of arthritis in CIA mice, accompanied by a decrease in the expression of IL-17 and RANKL and an increase in the expression of OPG. Furthermore, IL-35 dose-dependently inhibited the expression of RANKL and increased the expression of OPG in cultured FLS cells. CONCLUSION: IL-35 inhibits RANKL expression and increases OPG expression in CIA mice. IL-35 may be used for treating rheumatoid arthritis.
27680539 Inflammatory biomarkers, disease activity index, and self-reported disability may be predi 2017 Mar The chikungunya virus (ChikV) is a reemerging mosquito-borne pathogen that causes disabling chronic arthritis. The relationship between clinical evolution and inflammatory biomarkers in patients with ChikV-induced arthritis has not been fully described. We performed a prospective case series to evaluate the association among joint involvement, self-reported disability, and inflammatory biomarkers. Patients with ChikV infection were followed for 1 year. Joint involvement and self-reported disability were evaluated with disease activity index 28 (DAS-28) and World Health Organization Disablement Assessment Schedule II (WHODAS-II). Interleukin-6 (IL-6), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and rheumatoid factor (RF) were used as biomarkers. Ten patients with mean age 48 ±15.04 years were included. Symptoms at diagnosis were fever, arthralgias, myalgias, rash, arthritis, nausea, vomiting, and back pain. Polyarticular involvement was present in seven cases. At diagnosis, measures were as follows: DAS-28, 5.08±1.11; WHODAS-II score, 72.3±10.3 %; CRP, 5.09±7.23 mg/dL; ESR, 33.5±17.5 mm/h; RF, 64±21.7 IU/mL; and IL-6, 17.6±10.3 pg/mL. Six patients developed subacute and chronic symptoms. During follow-up, DAS-28 index, WHODAS-II score, ESR, and IL-6 were statistically different in patients with subacute and chronic symptoms compared to those who resolved in the acute phase (p < 0.05). DAS-28 index, WHODAS-II score, and IL-6 were related to chronicity of articular symptoms and could be used as predictors of ChikV-induced arthritis.
27438468 Chronic Calcium Channel Inhibitor Verapamil Antagonizes TNF-α-Mediated Inflammatory React 2016 Oct It is well established that the tumor necrosis factor-α (TNF-α) plays a dominant role in rheumatoid arthritis (RA). Calcium channel is recently reported to be closely associated with various inflammatory diseases. However, whether chronic calcium channel blocker verapamil plays a role in RA still remains unknown. To investigate the role of verapamil in antagonizing TNF-α-mediated inflammation reaction and the underlying mechanisms, bone marrow-derived macrophages (BMDM) cells were cultured with stimulation of TNF-α, in the presence or absence of verapamil. Inflammation-associated cytokines, including IL-1, IL-6, inducible nitric oxide synthase 2 (NOS-2), and cyclooxygenase-2 (COX-2), were assessed, and verapamil suppressed TNF-α-induced expression of inflammatory cytokines. Furthermore, collagen-induced arthritis (CIA) mice models were established, and arthritis progression was evaluated by clinical and histological signs of arthritis. Treatment of verapamil attenuated inflammation as well as joint destruction in arthritis models. In addition, activity of NF-kB signaling pathway was determined both in vitro and in mice arthritis models, and verapamil inhibited TNF-α-induced activation of NF-kB signaling both in vitro and in mice models. Collectively, chronic calcium channel blocker verapamil may shed light on treatment of inflammatory arthritis and provide a potential therapeutic instrument for RA in the future.
26183428 Association between arthritis score at the onset of the disease and long-term locomotor ou 2015 Jul 17 INTRODUCTION: To investigate the connection between the intensity of initial symptoms of inflammation and locomotor outcome in rheumatoid arthritis, we examined the relationship between long-term locomotor abnormalities and signs of inflammation at the onset of the disease in adjuvant-induced arthritis (AIA) in rats. METHODS: The arthritis score and hind-paw diameter were followed from immunization to day 195 (~7 months). At this time, locomotion was recorded during forced treadmill walking using 3D motion technology before radiographic scoring of hind limb joint damage. Many locomotor parameters were analyzed including time and length parameters, limbs kinematics, lateral paw position at toe off, maximal hind-paw elevation and posture. Ankle mobility was assessed from range of motion (ROM) of the joint during locomotion. Experiments were run in AIA (n = 18) and age-matched non-AIA rats (n = 8). RESULTS: All AIA rats exhibited signs of inflammation at day 14 with a peak of inflammatory symptoms at day 22 post-immunization. After the first episode of inflammation, 83 % of AIA rats demonstrated recurrent disease (from week 6 to week 23). The frequency of inflammatory episodes (1 to 5) was not linked to the arthritis score at day 22. At day 195 post-immunization, AIA rats showed significantly impaired locomotion and radiographic lesions as compared to control rats. Significant relationships were observed between most locomotion-related parameters and concurrent ROM of ankle, which correlated negatively with the radiographic score. ROM of ankle at day 195 correlated negatively with both the arthritis score and hind-paw diameter measured at day 14, 22 and 30 post-immunization. CONCLUSION: Decreased ankle mobility can be considered a driver of locomotion impairment in AIA. In this model, the severity of the initial inflammatory symptoms had a good prognostic value for long-term locomotor outcome.
26478088 Fructose 1,6-bisphosphate, a high-energy intermediate of glycolysis, attenuates experiment 2015 Oct 19 Fructose 1,6-bisphosphate (FBP) is an endogenous intermediate of the glycolytic pathway. Exogenous administration of FBP has been shown to exert protective effects in a variety of ischemic injury models, which are attributed to its ability to sustain glycolysis and increase ATP production. Here, we demonstrated that a single treatment with FBP markedly attenuated arthritis, assessed by reduction of articular hyperalgesia, joint swelling, neutrophil infiltration and production of inflammatory cytokines, TNF and IL-6, while enhancing IL-10 production in two mouse models of arthritis. Our mechanistic studies showed that FBP reduces joint inflammation through the systemic generation of extracellular adenosine and subsequent activation of adenosine receptor A2a (A2aR). Moreover, we showed that FBP-induced adenosine generation requires hydrolysis of extracellular ATP through the activity of the ectonucleosides triphosphate diphosphohydrolase-1 (ENTPD1, also known as CD39) and ecto-5'-nucleotidase (E5NT, also known as CD73). In accordance, inhibition of CD39 and CD73 abolished anti-arthritic effects of FBP. Taken together, our findings provide a new insight into the molecular mechanism underlying the anti-inflammatory effect of FBP, showing that it effectively attenuates experimental arthritis by activating the anti-inflammatory adenosinergic pathway. Therefore, FBP may represent a new therapeutic strategy for treatment of rheumatoid arthritis (RA).
27572325 Malignancy incidence in patients with psoriatic arthritis: a comparison cohort-based incid 2016 Oct Malignancy is a major cause of death in patients with inflammatory disease. The risk of individual malignancies is altered in some inflammatory diseases, such as rheumatoid arthritis and psoriasis. This study aimed to examine malignancy incidence in patients with psoriatic arthritis (PsA), a related inflammatory disease. Institutional cancer registry and medical record linkage systems were retrospectively reviewed in a population-based incidence cohort of 217 patients with PsA and 434 age- and sex-matched comparators. Malignancy rates were compared using adjusted Cox models. Incidence of overall malignancy (excluding NMSC; hazard ratio (HR) 1.64; 95 % confidence interval (CI) 1.03-2.61) and breast cancer (HR 3.59; 95 % CI 1.22-10.61), but not NMSC (HR 1.23; 95 % CI 0.72-2.09), were significantly elevated in the PsA cohort. Age and female sex were similar predisposing risk factors in both cohorts. The overall incidence of malignancy, as well as the risk of breast cancer, was higher in patients with PsA than in the general population.