Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
24129140 Is reduction or discontinuation of therapy an acceptable possibility in psoriatic arthriti 2013 Jul Remission in psoriatic arthritis (PsA), albeit variably defined, is a desirable and achievable state, especially in the era of biologic therapy. Historically, studies have used remission criteria derived from rheumatoid arthritis (RA), which indicate that remission is seen in a greater percentage of patients than in RA, including the possibility of drug-free remission in some patients. The Minimal Disease Activity (MDA) measure developed by the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) is a currently acceptable goal of therapy, taking into account PsA-specific elements such as skin disease and enthesitis. Newer PsA composite measures which include thresholds for remission are under development and are now included in prospective clinical trials. Once remission is achieved and sustained on therapy, a natural question is whether treatment can be reduced or discontinued to avoid treatment toxicities and costs. Exploratory data are being analysed from observational cohorts regarding the capacity to reduce treatment dose, dose frequency, or discontinue use of a medication whilst maintaining remission. A controlled dose-reduction and discontinuation study design is outlined, which may provide controlled evidence for such a paradigm of treatment.
21229360 Schistosoma mansoni infection: an immune complex disease presenting with polyarthritis. 2013 May Schistosomiasis or bilharzia is a parasitic disease found in tropical countries. Most infections are subclinical but may progress to chronic form characterized most frequently by the presence of liver involvement and portal hypertension. We report a patient that presented chronic polyarthritis with positive rheumatoid factor. During investigation, increased liver enzymes, negative hepatitis serologies and signs of portal hypertension on an ultrasound examination raised suspicion of S. mansoni infection. We will discuss pathophysiology and clinical manifestations of S. mansoni infection with special attention to articular involvement.
25173950 Pachydermodactyly: a review. 2014 Synovitis is the characteristic feature of inflammatory joint disease. If synovitis is localized to interphalangeal joints, rheumatoid arthritis, psoriatic arthritis, and juvenile idiopathic arthritis are among the most common differential diagnoses. The absence of pain, tenderness, and limitation of function despite progressive swelling of proximal interphalangeal joints suggests an alternative diagnosis, for example pachydermodactyly (PDD). This is a benign disease, associated with asymptomatic, progressive swelling of periarticular soft tissue, which usually occurs in young males. PDD is probably the result of repetitive mechanical stimulation. One hundred and twenty-one cases have been reported in the literature. Some of these were initially misdiagnosed and treated for inflammatory arthritis. We provide a comprehensive review of the literature on pachydermodactyly to promote awareness of this rare but important differential diagnosis of arthritis.
23476694 Mediators of inflammation-induced bone damage in arthritis and their control by herbal pro 2013 Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation of the synovial joints leading to bone and cartilage damage. Untreated inflammatory arthritis can result in severe deformities and disability. The use of anti-inflammatory agents and biologics has been the mainstay of treatment of RA. However, the prolonged use of such agents may lead to severe adverse reactions. In addition, many of these drugs are quite expensive. These limitations have necessitated the search for newer therapeutic agents for RA. Natural plant products offer a promising resource for potential antiarthritic agents. We describe here the cellular and soluble mediators of inflammation-induced bone damage (osteoimmunology) in arthritis. We also elaborate upon various herbal products that possess antiarthritic activity, particularly mentioning the specific target molecules. As the use of natural product supplements by RA patients is increasing, this paper presents timely and useful information about the mechanism of action of promising herbal products that can inhibit the progression of inflammation and bone damage in the course of arthritis.
24823363 Citrullination of collagen II affects integrin-mediated cell adhesion in a receptor-specif 2014 Aug Citrullinated collagen II (CII) is a well-known autoantigen in rheumatoid arthritis (RA). However, the direct effects of CII citrullination on cell behavior have not been described. To study whether citrullination of CII could affect cellular functions, we measured the adhesion of 3 different cell types (human Saos2 osteosarcoma cells, human synovial fibroblasts, and rat mesenchymal stem cells) with impedance-based technology. The binding of different collagen receptor integrins to citrullinated collagen was studied by CHO cell lines, each overexpressing 1 of the 4 human collagen receptors on the cell surface, and with solid-phase binding assays, using the recombinant human integrin α1I, α2I, α10I, and α11I domains. Collagen citrullination decreased the adhesion of synovial fibroblasts ∼50% (P<0.05) and mesenchymal stem cells ∼40% (P<0.05) by specifically decreasing the binding of integrins α10β1 and α11β1 to arginine-containing motifs, such as GFOGER. In contrast, citrullination had only a minor effect on the function of α1β1 and α2β1 integrins, which have been reported to play a critical role in regulating leukocyte function. Molecular modeling was used to explain the detected functional differences at the structural level. Given that the integrins regulate cell metabolism, proliferation, and migration, we suggest that collagen citrullination modifies the pathogenesis of RA. Here, CII citrullination was shown to decrease the survival of mesenchymal stem cells.
24803296 Berberine ameliorates collagen-induced arthritis in rats associated with anti-inflammatory 2014 Oct Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by inflammation and joint destruction. In this study, we explored the effect of berberine on rats with bovine type II collagen-induced arthritis (CIA), an animal model for RA. Following treatment, berberine attenuates arthritic scores and suppresses collagen-specific immune responses in CIA rats. Compared with the un-treated CIA group, berberine reversed pathological changes, which showed a significant improvement in synovial hyperplasia and inflammatory infiltration. The expression levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, IL-17 and vascular endothelial growth factor (VEGF) were obviously reduced in the sera of berberine-treated rats (all P<0.05). Moreover, berberine showed marked inhibition of the expression of VEGF and CD34 (all P<0.05). Interestingly, berberine significantly suppresses p-ERK, p-p38 and p-JNK activation (all P<0.05), which may partially explain the anti-RA activity of berberine. These results suggest that berberine ameliorates CIA in rats associated with anti-inflammatory and anti-angiogenic effects, which might be of great therapeutic value for RA.
24213625 Advances in the pathogenesis and treatment of systemic juvenile idiopathic arthritis. 2014 Jan Systemic juvenile idiopathic arthritis (s-JIA) is clinically distinct from other types of JIA. It is typified by extraarticular features such as quotidian fevers, rash, splenomegaly, lymphadenopathy, laboratory abnormalities (including leukocytosis, thrombocytosis, anemia, hyperferritinemia, and elevated inflammatory markers), and a close association with the macrophage activation syndrome. Recent investigations have highlighted dysregulation of the innate immune system as the critical pathogenic driver of s-JIA. Key innate immune mediators of s-JIA are the macrophage-derived cytokines interleukin-1 (IL-1) and IL-6. Increased understanding of the roles of IL-1 and IL-6 in the pathogenesis of s-JIA has led to major changes in therapeutic options. Until recently, the most commonly used medications included corticosteroids, methotrexate, and tumor necrosis factor (TNF) inhibitors, which are incompletely effective in most cases. Newer biologic agents targeting IL-1 and IL-6 have proven very effective in treating s-JIA and in minimizing corticosteroid exposure. Here we review recent advances in the understanding of the pathogenesis of s-JIA and the recent clinical trials that have revolutionized the care of children with s-JIA.
24347977 Abatacept in psoriatic arthritis: Case report and short review. 2013 Dec Psoriatic arthritis (PsA) is a chronic inflammatory disease affecting about 6-10% of patients with cutaneous psoriasis. According to current knowledge, activated T-cells seem to play a pivotal role in the pathogenesis of both psoriasis and PsA. Abatacept is a novel biologic agent selectively designed to interfere with T-cells co-stimulation. Structurally, it is a soluble, fully human fusion protein consisting of the extracellular domain of CTLA-4 (Cytotoxic T-Lymphocyte Antigen 4) linked to a modified Fc portion of human IgG1. Abatacept is now approved as a first-line treatment for rheumatoid arthritis (RA), but preliminary data disclose a potential role of abatacept in the treatment of other autoimmune diseases. In this article, we report a case of successful treatment with abatacept of a psoriatic arthritis patients who developed adverse drug reactions (ADRs) to medication commonly used in PsA, including three different anti-TNF-α agents. In addition, we review the scientific evidences supporting a possible role of abatacept in treatment of patients with psoriasis and PsA and the paradox of abatacept-induced psoriasis.
24832356 Chemopreventive effects of a curcumin-like diarylpentanoid [2,6-bis(2,5-dimethoxybenzylide 2015 Jul AIM: Synovial fibroblast has emerged as a potential cellular target in progressive joint destruction in rheumatoid arthritis development. In this study, BDMC33 (2,6-bis[2,5-dimethoxybenzylidene]cyclohexanone), a curcumin analogue with enhanced anti-inflammatory activity has been synthesized and the potency of BDMC33 on molecular and cellular basis of synovial fibroblasts (SF) were evaluated in vitro. METHODS: Synovial fibroblast cells (HIG-82) were cultured in vitro and induced by phorbol-12-myristate acetate (PMA) to stimulate the expression of matrix metalloproteinase (MMPs) and pro-inflammatory cytokines. The protective effects of BDMC33 were evaluated toward MMP activities, pro-inflammatory cytokine expression and nuclear factor kappa-B (NF-κB) activation by using various bioassay methods, including zymography, Western blotting, reverse transcription polymerase chain reaction, immunofluorescense microscopy and electrophoretic mobility shift assay. RESULTS: The results showed that BDMC33 significantly inhibited the pro-gelatinase B (pro-MMP-9) and collagenase activities via suppression of MMP-1 in activated SF. In addition, BDMC33 strongly suppressed MMP-3 gene expression as well as inhibited COX-2 and IL-6 pro-inflammatory gene expression. We also demonstrated that BDMC33 abolished the p65 NF-κB nuclear translocation and NF-κB DNA binding activity in PMA-stimulated SF. CONCLUSIONS: BDMC33 represents an effective chemopreventive agent and could be used as a promising lead compound for further development of rheumatoid arthritis therapeutic intervention.
24998233 Serum levels of interleukin-1 beta, interleukin-6 and melatonin over summer and winter in 2014 Jun OBJECTIVE: To observe the seasonal changes in serum levels of interleukin-1 beta (IL-1β), interleukin-6 (IL-6) and melatonin (MT) in Bizheng rat model, and explore the relationship between MT and the pathogenesis of rheumatoid arthritis. METHODS: One hundred and sixty Sprague-Dawley rats were randomly divided into four groups in summer (n=80) and winter (n=80) respectively: normal group, collagen-induced arthritis (CIA) model group, operation group, and sham-operation group (n=20 in each group). The CIA model group was injected with collagen emulsion at the base of the tail to induce arthritis. The rats in the operation group received pineal gland resection, and 7 days after the first operation, underwent testectomy or oophorectomy. The rats in the sham-operation group were operated to ligature the sagittal sinus, without extracting the pineal gland. After the operations, the operation group and the sham-operation group both were immunized as the CIA group was. The serum levels of IL-1β, IL-6 and MT in different groups were measured by radioimmunoassay. RESULTS: Compared with the normal group, the serum levels of IL-1β and IL-6 increased in the CIA model, operation, and sham-operation groups both in summer and in winter (IL-1β in summer, P=0.008, P<0.01, P=0.012; IL-1β in winter, P=0.019, P<0.01, P=0.027; IL-6 in summer, P=0.028, P<0.01, P=0.024; IL-6 in winter, P=0.006, P<0.01, P=0.008). In the operation group, the serum levels of IL-1β and IL-6 in winter were higher than in summer, but with no statistically significant differences (P=0.844, 0.679). Compared with the normal group, the serum level of MT significantly increased in summer and winter in both the CIA model group (P=0.002, 0.008) and the sham-operation group (P=0.003, 0.007), while significantly decreased in the operation group (P=0.023, 0.003). There was no significant difference in MT level in the operation group between summer and winter (P=0.947). CONCLUSIONS: The increase of serum levels of IL-1β and IL-6 may exacerbate the inflammatory reaction and cause a more severe condition in the rheumatoid arthritis. The concentrations of IL-1β, IL-6, and MT correspond with the change of seasons, confirming that there are connections between nature and human body.
25460084 Paradoxical effects of human adipose tissue-derived mesenchymal stem cells on progression 2014 Nov We evaluated the therapeutic effect of human adipose tissue-derived mesenchymal stem cells (hAd-MSCs) in a SKG arthritis model, a relevant animal model for human rheumatoid arthritis. hAd-MSCs were administered intraperitoneally into the mice for five consecutive days from on day 12 or 34 after arthritis induction, when the average clinical score was 0.5 or 5, respectively. They remarkably suppressed arthritis when administered on day 12. Disease suppression was correlated with reduction of pro-inflammatory cytokines and with increased levels of TGF-β and IL-10 from splenocytes. However, when hAd-MSCs were administered on day 34, the clinical scores were not improved, the histopathological scores were aggravated, and cytokine profiles were differed. Thus, hAd-MSCs showed paradoxical effects, according to the disease phase when they were administered. These suggest that the same cells acted differently depending on the disease progress, and cautions should be paid for safe and effective use of MSCs.
23527805 Arthroscopic debridement and synovium resection for inflammatory hip arthritis. 2013 Mar OBJECTIVE: To evaluate the efficacy of arthroscopic surgery in inflammatory hip arthritis. METHODS: A retrospective clinical study was conducted inspecting 40 hips in 36 patients of inflammatory arthritis. There were 17 cases of ankylosing spondylitis, 11 cases of rheumatoid arthritis, and 8 cases of psoriatic arthritis. The joints were irrigated and the inflamed tissues were debrided with anthroscopy. The patients were followed up with Harris hip score, Oxford hip score, Visual Analog Scale (VAS), and magnetic resonance imaging (MRI). Statistical analysis was performed using Student t test. RESULTS: All of the 36 cases were followed up for 46-103 months, averaging 67.2±8.4 months. Harris and Oxford scores increased from 66.9±12.1 and 69.4±16.4 before operation to 78.4±19.3 and 80.2±18.8 after operation, respectively (P<0.05). VAS score decreased from pre-operative 8.5±2.5 to post-operative 7.2±2.5 (P<0.05). All the patients showed improved joint range of motion. MRI revealed alleviation of hip synovitis. The results were classified as excellent in 8 patients, good in 17 patients, fair in 8 patient, and poor in 3 according to Harris hip score. Twenty-seven patients were satisfied with the operative outcomes as they regained normal daily activities. CONCLUSIONS: Arthroscopy-assisted joint debridement and synovium resection is an effective procedure for hip lesion in inflammatory arthritis. The inflammatory lesion might be thereby controlled and the symptoms be relieved.
22362575 Role of IL-17 in psoriasis and psoriatic arthritis. 2013 Apr The role of T cell subpopulations in human disease is in a transition phase due to continuous discovery of new subsets of T cell, one of which is Th17, characterized by the production of signature cytokine IL-17. In the last couple of years, many articles are coming out on the role of Th17 and its signature cytokine IL-17 in different autoimmune diseases like rheumatoid arthritis, psoriasis, psoriatic arthritis (PsA), SLE and multiple sclerosis. Psoriasis and PsA are immune-mediated diseases, affecting the skin and joints, respectively. Initially, it was thought that psoriasis and PsA were Th1-mediated diseases; however, studies in knockout animal models (IL-17 knockout mice) as well as human experimental data indicate that Th17 and its signature cytokine IL-17 have a critical role in the pathogenesis of psoriatic disease. Th17 cells have been identified from the dermal extracts of psoriatic lesions. Subsequently, our research group has substantiated this observation that Th17 cells are enriched in the papillary dermis of psoriatic plaques and in freshly isolated effector T lymphocytes from the synovial fluid of PsA patients, and we have reported that the majority of these CD4 + IL-17+ T cells are of memory phenotype (CD4RO(+)CD45RA(-)CD11a(+)). Recent reports also suggest that the synovial tissue in psoriatic arthritis is enriched with IL-17R, and its most well recognized receptor IL-17RA is functionally active in psoriatic arthritis. In this review article, we have discussed the role of IL-17 in psoriatic disease and have narrated about the novel IL17/IL-17R antibodies currently in preparation for its therapeutic uses in autoimmune diseases.
24135236 (E)-3-(3,4-Dimethoxyphenyl)-1-(5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)prop-2-en-1-one amel 2013 Dec Our previous report has shown a natural pyranochalcones-derived compound, (E)-3-(3,4-Dimethoxyphenyl)-1-(5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)prop-2-en-1-one (5b), that exerted protection against carrageenan-induced hind paw edema and adjuvant-induced arthritis. In this study, collagen-induced arthritis (CIA) model was used to further examine the anti-arthritic effects of 5b in vivo; the underlying molecular mechanisms of action were also investigated using a murine monocytic cell line, RAW264.7 cells. Here we showed that oral administration of 5b (20mg/kg) significantly suppressed the progression of arthritis. Improvement in disease severity was accompanied by inhibition of CD68-positive cells in knee joint and reduced pro-inflammatory cytokines TNF-α, IL-1β and IL-6 in serum. In vitro, 5b suppressed expressions of iNOS, cyclooxygenase-2 (COX-2), TNF-α, IL-6 and IL-1β as well as productions of nitric oxide (NO) and prostaglandin E2 (PGE2) in lipopolysaccharide (LPS)-treated macrophages. This compound also significantly suppressed LPS-induced NF-κB activation, including phosphorylation of I-κB, degradation of I-κB, and nuclear translocation of p65 and p50. Treatment with 5b also blocked LPS-induced expression of TLR4 remarkably, suppressed degradation of IRAKs and phosphorylations of JNK and ERK, but had little effect to p38 kinase activation. These findings indicated that 5b might be a therapeutic agent for rheumatoid arthritis, and exerted an anti-inflammatory effect mainly through mediating TLR4, NF-κB and ERK/JNK signaling pathways in monocytes.
25780785 The role of phosphodiesterase inhibitors in the management of pulmonary vascular diseases. 2014 Phosphodiesterase inhibitors (PDE) can be used as therapeutic agents for various diseases such as dementia, depression, schizophrenia and erectile dysfunction in men, as well as congestive heart failure, chronic obstructive pulmonary disease, rheumatoid arthritis, other inflammatory diseases, diabetes and various other conditions. In this review we will concentrate on one type of PDE, mainly PDE5 and its role in pulmonary vascular diseases.
24782192 Whole blood gene expression profiling predicts therapeutic response at six months in patie 2014 May OBJECTIVE: To determine whether gene expression profiles identified in peripheral whole blood samples could be used to determine therapeutic outcome in a cohort of children with newly diagnosed polyarticular juvenile idiopathic arthritis (JIA). METHODS: Whole blood samples from the Trial of Early Aggressive Therapy (TREAT) in JIA patients were analyzed on Illumina microarrays, and differential gene expression was compared to expression in healthy controls. Microarray results were validated by real-time quantitative polymerase chain reaction in an independent cohort of samples. Pathway analysis software was used to characterize gene expression profiles. Support vector machines were used to develop predictive models for different patient classes. RESULTS: Differential gene expression profiles for rheumatoid factor (RF)-positive and RF-negative patients were remarkably similar. Pathway analysis revealed a broad range of affected pathways, consistent with current mechanistic theories. Modeling showed that the prognosis at 6 months was strongly linked to gene expression at presentation, irrespective of treatment. CONCLUSION: Gene expression is linked to therapeutic outcome, and gene expression in the peripheral blood may be a suitable target for a prognostic test.
25535773 Diagnostic utility of major salivary gland ultrasonography in primary Sjögren's syndrome. 2015 Jan OBJECTIVES: To investigate major salivary gland ultrasonography (US) in relation to symptoms and findings of oral and ocular dryness, and autoimmune disease, for potential use in diagnosis and follow-up of patients with primary Sjögren's syndrome (pSS). METHODS: Patients with pSS were recruited from the Department of Rheumatology, Haukeland University Hospital. The parotid and submandibular salivary glands were examined by US using a simplified scoring system for glandular homogeneity and hypoechogenic areas. Scans were graded on a scale 0-3, grades 0-1 considered corresponding to normal/non-specific changes and grades 2-3 to pathological changes. Sicca symptoms of the mouth and eyes, salivary gland capacity, tear secretion, minor salivary gland inflammation, serum autoantibodies, and fatigue were also investigated. RESULTS: US was performed in 97 patients. Oral and ocular sicca symptoms correlated with US score and decreased saliva levels. Fatigue VAS correlated with oral sicca symptoms but was inversely correlated with age. Patients with normal/non-specific US findings tended to be older than patients with pathological US findings. US score correlated with unstimulated and stimulated salivary secretion and tear secretion. Minor salivary gland inflammation correlated with major salivary gland US findings, and lymphoid organisation, germinal centre (GC)-like structures, in the minor salivary gland tissue biopsies was seemingly related to US pathology. Serum autoantibodies against Ro/SSA and/or La/SSB were associated with US pathology. CONCLUSIONS: US findings in major salivary glands correlate with subjective and objective oral and ocular items as well as systemic autoimmune features of pSS. US represents a useful imaging tool for diagnostics and follow-up of pSS.
24287189 Sjögren's syndrome: an update on epidemiology and current insights on pathophysiology. 2014 Feb Primary Sjögren's syndrome (pSS) is an autoimmune chronic inflammatory disorder affecting 0.2% to 3.0% of the population, with a 9:1 female to male ratio. Features are oral and ocular dryness, local and systemic autoantibody production, and progressive focal mononuclear cell infiltration in the affected salivary and lacrimal glands. Lymphoma is the most severe complication of pSS, occurring in 4% to 5% of patients. Genetic studies identified an association with HLA and susceptibility genes in cytokine genes and genes involved in B-cell differentiation. Genetic variations may help explain why disease manifestations differ among patients and supports the hypothesis of certain distinct disease phenotypes.
23674107 Comparing nebulized water versus saline after laryngeal desiccation challenge in Sjögren' 2013 Nov OBJECTIVES/HYPOTHESIS: This study examined the effects of a laryngeal desiccation challenge and two nebulized hydration treatments on phonation threshold pressure (PTP), vocal effort, and throat dryness in patients with chronic airway dryness. STUDY DESIGN: Double-blind, within-subjects crossover design. METHODS: Eleven individuals with Primary Sjögren's Syndrome received a 15-minute laryngeal desiccation challenge (breathing dry air-<1% relative humidity-transorally), followed by nebulized isotonic saline or nebulized water treatments (3 mL) on 2 consecutive weeks. PTP, as well as self-perceived vocal effort, mouth, and throat dryness were assessed before and after the desiccation challenge, and at 5, 35, and 65 minutes after the nebulized treatment. RESULTS: The laryngeal desiccation challenge produced statistically significant increases in PTP, vocal effort, and mouth and throat dryness (P < 0.05). Nebulized saline produced greater-but not statistically significant-treatment effects than water. PTP was more correlated with throat dryness than vocal effort. CONCLUSION: Patients with chronic airway dryness experienced phonatory changes following dry air exposure. Nebulized isotonic saline may offset this effect. Future research should explore dose-response relationships among dry air exposure, nebulized treatments, voice change, and self-perceived throat dryness.
25316606 Sjögren Syndrome-associated lymphomas: an update on pathogenesis and management. 2015 Feb Primary Sjögren Syndrome (pSS) is an autoimmune disease associated with an increased risk of lymphoma. Lymphomas complicating pSS are mostly low-grade B cell non-Hodgkin lymphomas, predominantly of marginal zone histological type. Mucosal localization is predominant, notably mucosa-associated lymphoid tissue lymphomas. Lymphomas often develop in organs where pSS is active, such as salivary glands. Germinal centre (GC)-like structures, high TNFSF13B (BAFF) and Flt3-ligand (FLT3LG) levels and genetic impairment of TNFAIP3 are new predictors of lymphoma development. These new findings allow a better understanding of the pathogenic mechanisms leading to lymphoma. We propose the following scenario: auto-immune B cells with rheumatoid factor (RF) activity are continuously stimulated by immune complexes containing antibodies against more specific auto-antigens, such as SSA/Ro, SSB/La or others. Germline abnormality of TNFAIP3 leads to a decreased control of the NF-kB pathway and thus promotes survival of B cells and oncogenic mutations especially in GC structure. Moreover, B cells are stimulated by a positive loop of activation induced by BAFF secretion. Thus, lymphomagenesis associated with pSS exemplifies the development of antigen-driven B-cell lymphoma. The control of disease activity by a well-targeted immunosuppressor is the primary objective of the management of the patient in order to repress chronic B cell stimulation.