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ID PMID Title PublicationDate abstract
28572803 Insulin-Like Growth Factor Binding Protein 6 in Rheumatoid Arthritis: A Possible Novel Che 2017 OBJECTIVES: Immune cell migration from the bloodstream to target tissues is a hallmark of rheumatoid arthritis (RA) pathogenesis. The role of chemoattractants, mainly chemokines, and their possible targeting for therapeutic purposes have been under intense investigation over the last few years but the results were not as satisfactory as expected. The insulin-like growth factor binding protein 6 (IGFBP6), a direct inhibitor of insulin-like growth factor (IGF)-II, also exerts IGF-independent effects including tumor cell migration in vitro. We aimed to assess the expression of this protein in serum, synovial fluid, and synovial tissue (ST) of RA patients and to identify its possible chemotactic role in this disorder. METHODS: IGFBP6 was measured in RA patients and healthy donors (HD) sera by Luminex xMAP(®) technology and in ST of RA patients and osteoarthritis (OA) controls by immunofluorescence. The identification of circulating IGFBP6(+) cells was evaluated by flow cytometry and an in vitro migration assay was arranged. RESULTS: We demonstrated that IGFBP6 is able to induce greater in vitro migration of RA as compared to HD and OA T lymphocytes and is overexpressed in serum and ST of RA patients. This in vitro chemotactic activity can be partially inhibited by dexamethasone. CONCLUSION: Our findings suggest a pathogenic role of IGFBP6 in RA and support its possible targeting for therapeutic purposes.
28516086 Can Synovial Pathobiology Integrate with Current Clinical and Imaging Prediction Models to 2017 Although great progress has been made in the past decade toward understanding the pathogenesis of rheumatoid arthritis (RA), clinicians remain some distance from a goal of personalized health care. The capacity to diagnose RA early, predict prognosis, and moreover predict response to biologic therapies has been a research focus for many years. How currently available clinical prediction models can facilitate such goals is reviewed in this article. In addition, the role of current imaging techniques in this regard is also discussed. Finally, the authors review the current literature regarding synovial biomarkers and consider whether integration of synovial pathobiology into clinical prediction algorithms may enhance their predictive value.
29056774 Glucocorticoid management in rheumatoid arthritis: morning or night low dose? 2017 Morning symptoms of rheumatoid arthritis (RA) are linked to circadian increase of night inflammation, supported by inadequate cortisol secretion in active disease. Therefore, exogenous glucocorticoid administration in RA is recommended by EULAR and ACR from the beginning of the diagnosis, since may partially act like a "replacement therapy". In addition, the prevention/treatment of the night up-regulation of the immune/inflammatory reaction has been shown more effective when exogenous glucocorticoid administration is managed with a night-time-release formulation. Despite a considerably higher cost than conventional prednisone (immediate release), chronotherapy with night-time-release prednisone has been recognized a cost-effective option for RA patients not on glucocorticoids who are eligible for therapy with biologic disease-modifying antirheumatic drugs (DMARDs). Interestingly, since different cell populations involved in the inflammatory process are particularly activated during the night (i.e. monocytes, macrophages), other therapeutical approaches used in RA, such as conventional DMARDs and non-steroidal anti-inflammatory drugs (NSAIDs) should follow the same concepts of glucocorticoid chronotherapy. Therefore, bedtime methotrexate chronotherapy was found to better manage RA symptoms, and several available NSAIDs (i.e. indomethacin, aceclofenac, ketoprofen, flurbiprofen, lornoxicam) have been recently modified in their formulation, in order to obtain more focused night action.
28344422 Impaired Left Ventricular Diastolic Functions and Thickened Epicardial Adipose Tissue in R 2017 Mar BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory disease that is known to be associated with high cardiovascular (CV) morbidity and mortality. In this study, we aimed to demonstrate whether RA disease activity reflected with disease activity score-28 (DAS-28) had an impact on left ventricular diastolic functions and epicardial adipose tissue (EAT) thickness in RA patients with no traditional CV risk factors. METHODS: In this retrospective study, 41 patients newly diagnosed with RA were included. In addition to medical history, detailed physical examination findings and laboratory tests, left ventricular systolic and diastolic functions, chamber dimensions, and EAT thickness were evaluated with transthoracic echocardiography in the study population. RESULTS: This study included 41 subjects with a median age of 45 years (38.00-55.50), of which 29.27% were male. In the binomial logistic regression analysis, DAS-28 score was found to be an independent associate of diastolic dysfunction, Additionally, DAS-28 was found to be independently associated with EAT thickness. CONCLUSIONS: Patients with high DAS-28 score should be evaluated thoroughly for CV disease, and patients should undergo advanced diagnostic studies as required and receive appropriate treatment.
28565826 Transcriptional profiling of leukocytes from rheumatoid arthritis patients before and afte 2017 May Anti-nuclear antibodies (ANAs) may be induced in patients with rheumatoid arthritis (RA) receiving anti-tumor necrosis factor (TNF) therapy with TNF inhibitors (TNFi), etanercept, infliximab or adalimumab. In the present study, 11 patients who were TNFi drug naive were started on TNFi at a time of high disease activity. Of these, all cases were positive for rheumatoid factor and 9 cases tested were positive for anti-citrullinated peptide (anti-CCP) antibodies prior to TNFi treatment. Peripheral blood mononuclear cells (PBMCs) and serum were collected from all patients before and after TNFi therapy. Serum was assayed for ANAs over time. Total cellular RNA was extracted from PBMCs and assessed using Illumina arrays. Gene expression profiles were examined for alterations in key effector pathways. After 3 or more months on TNFi, 6 patients converted to ANA-positivity. Analysis of transcripts from patients with RA who converted to ANA-positivity after 3 months on TNFi identified complex gene expression profiles that reflected a reduction in cell adhesion, cell stress and lipid metabolism transcripts. In summary, unique transcriptional profiles in PBMCs from patients with RA were observed after TNFi therapy. This pilot study suggests that transcriptional profiling is a precise method of measuring the impact of TNFi therapies and reveals novel pathways that likely influence the immune response.
28698517 The Plasticity of Th17 Cells in the Pathogenesis of Rheumatoid Arthritis. 2017 Jul 10 Helper T (Th) cells play an important role in the pathogenesis of autoimmune diseases, including rheumatoid arthritis (RA). It has been revealed that Th17 cells can shift to Th1 cells (i.e., "nonclassic Th1 cells"), which are reported to be more pathogenic than Th17 cells per se. Thus, the association of Th cells in the pathogenesis of autoimmune disease has become more complicated. We recently reported using peripheral blood from untreated and early-onset RA patients that the ratio of CD161+Th1 cells (i.e., Th17-derived Th1 cells to CD161+Th17 cells) is elevated and that levels of interferon-γ (IFNγ)+Th17 cells are inversely correlated with levels of anti-CCP antibodies. Here, we review the plasticity of Th17 cells in the pathogenesis of RA, suggesting possible implications for novel therapies.
28357081 Lectin, galactoside-binding, soluble, 3 rs4652 A/C gene variation and the risk for rheumat 2017 Feb Rheumatoid arthritis (RA) is a complex genetic disease. The lectin, galactoside-binding, soluble, 3 (LGALS3) gene, encodes a member of the galectin family of carbohydrate binding proteins, and is one of the best examples of a non-human leukocyte antigen gene associated with a risk for RA in various populations. In the current study, the association between LGALS3 rs4652 gene polymorphism and RA was examined. This case-control study was performed on the 120 patients with RA and 120 healthy subjects. Genomic DNA was extracted from whole blood, and gene polymorphism was tested using a tetra-primer amplification refractory mutation system-polymerase chain reaction. The results demonstrated that LGALS3 rs4652 AC genotype increased the risk of RA (OR=11.622, 95% CI=4.473-28.656; P=0.001) when compared with the AA genotype. However, the CC genotype and the C allele were not associated with RA. These findings indicated an association between LGALS3 rs4652 variation and the risk of RA in a sample of Iranian individuals. Further studies with larger sample sizes and populations of different ethnicities are required to validate our findings.
28321833 Depression Risk in Patients with Rheumatoid Arthritis in the United Kingdom. 2017 Jun INTRODUCTION: Rheumatoid arthritis (RA) is one of the most common chronic inflammatory diseases. The goal of this study was to analyze the risk of depression in patients diagnosed with RA and treated by general practitioners in the UK. METHODS: The present study included patients first diagnosed with RA between 2000 and 2014 (index date). Individuals were excluded if they had also been diagnosed with depression or if they had received therapy for depression at or prior to the index date. The primary outcome measure was the rate of patients with depression (ICD 10: F32, 33) within 5 years of the RA diagnosis. Demographic data included gender and age. Furthermore, a revised version of the Charlson comorbidity index was used as a generic marker of comorbidity. RESULTS: A total of 4187 patients were included in the study. After 5 years of follow-up, 23.7% of men and 36.5% of women had developed depression (log rank p value <0.001). Women were more likely to develop depression than men (HR 1.61, 95% CI 1.42-1.84). Age and Charlson comorbidity score had no significant impact on the risk of being diagnosed with this psychiatric disorder. CONCLUSION: Around 30% of RA patients developed depression within 5 years of the RA diagnosis. The depression risk was higher in women than in men. The current findings also indicate that improved detection and treatment of patients with both RA and depression are important.
29200618 Effects of individual and group exercise programs on pain, balance, mobility and perceived 2017 Nov [Purpose] To verify the effects of individual and group exercise programs on pain, balance, mobility and perceived benefits of rheumatoid arthritis patients (RA) with pain and foot deformities. [Subjects and Methods] Thirty patients with RA pain and foot deformity were allocated into two groups: G1: individual exercise program and G2: group exercise program. The variables analyzed were Numerical Rating Scale (NRS) for pain, Berg Balance Scale (BBS) for balance, Timed Up & Go Test (TUG) and Functional Reach (FR) for mobility, and Foot Health Status Questionnaire (FHSQ-Br) for perceived benefits. Both exercise programs consisted of functional rehabilitation exercises and self-care guidance aimed at reducing pain and improving balance and mobility. Intragroup comparisons of variables between A1 (pre-intervention) and A2 (post-intervention) were performed. [Results] Patients in both groups were similar in A1 (pre-intervention) in all the variables analyzed. Comparison between A1 and A2 for each variable showed improvement for G1 in the NRS, BBS, FR, TUG and in four out of ten domains of FHSQ-Br. G2 showed improvement in the NRS, BBS and eight out of ten domains of FHSQ-Br. [Conclusion] Both individual and group programs revealed benefits for patients with RA, however, group exercise programs showed better perception of benefits.
28417081 An ELISA protocol to improve the accuracy and reliability of serological antibody assays. 2017 To assay serum antibodies by indirect ELISA, it is critical to eliminate a variety of false positive and negative reactions attributed to the principle. These include 1) the background (BG) noise reaction caused by hydrophobic binding of immunoglobulin components in sample specimens to solid surfaces, 2) false positive reaction caused by non-specific binding of immunoglobulins to target-antigens by protein-protein interactions, and 3) other false positive and negative reactions caused by buffer components. No current blocking agents can prevent these false positive and negative reactions, and antibody assay results vary significantly depending on the buffer system used. To address these fundamental problems, we investigated all types of non-specific reactions involved in indirect ELISAs, and the blocking efficacy of current buffer systems and a newly developed ELISA buffer, ChonBlockâ„¢. The accuracy and reliability of these assay results were examined in detail by inhibition tests in individual buffer systems. Based on these studies, we are providing a definitive ELISA protocol for all users to improve ELISA technique and obtain accurate, reliable, and reproducible assay data against a variety of antigens.
29515750 [Ankylosing spondylitis associated with Still's disease: should it be considered a pathoph 2017 Ankylosing spondylitis is a chronic inflammatory rheumatism; it is part of the group of spondyloarthrites. General signs such as fever and weight loss are of little importance. Adult Still's disease is a rare systemic condition, a diagnosis of exclusion commonly characterized by high hectic fever, rash, arthritis and various systemic manifestations. Few cases of ankylosing spondylitis associated with adult Still's disease have been described in the literature. We here report the case of a 31-year old patient followed up for ankylosing spondylitis presenting with fever which had lasted for a long time and clinico-biological signs compatible with adult Still's disease. A possible pathophysiologic link between the two diseases may be suggested, even if their simultaneous occurrence has been rarely reported in the literature.
28684087 Anti-arthritic potential of marine macroalgae Turbinaria ornata in Complete Freund's Adjuv 2017 Oct 2 T. ornata a macroalgae rich in bioactive molecules possess various biological activities. Herein, the aim of the study is to evaluate the aqueous extract and the sulphated polysaccharide isolated from T. ornata for its anti-arthritic potential in Complete Freund's Adjuvant (CFA) induced arthritis in rats. Anti-arthritic potential of aqueous T. ornata (ATO) and T. ornata sulphated polysaccharide (TSP) was evidenced by the significant reduction in paw volume and arthritic score. Inflammatory and antioxidant markers were found to be restored in the drug treated groups which was found to be in line with dexamethasone a standard anti-inflammatory drug. The histopathological and radiological examination adds on the support to the above findings confirming the anti-arthritic potential of ATO and TSP. It is interesting to note that the sulphated polysaccharide inhibits inflammation and bone damage at very low dose itself. Hence, TSP could be considered as a better candidate in the management of chronic inflammatory diseases like rheumatoid arthritis.
31723711 A mode of error: Immunoglobulin binding protein (a subset of anti-citrullinated proteins) 2017 Dec Citrullinated Immunoglobulin Binding Protein (BiP) is a newly described autoimmune target in rheumatoid arthritis (RA), one of many cyclic citrullinated peptides(CCP or ACPA). BiP is over-expressed in RA patients causing T cell expansion and increased interferon levels during incubation for the QuantiFERON-Gold tuberculosis test (QFT-G TB). The QFT-G TB has never been validated where interferon is increased by underlying disease, as for example RA. Of ACPA-positive RA patients (n = 126), we found a 13% false-positive TB test rate by QFT-G TB. Despite subsequent biologic therapy for 3 years of all 126 RA patients, none showed evidence of TB without INH. Most of the false-positive RA patients after treatment with biologic therapy reverted to a negative QFT-G test. False TB tests correlated with ACPA level (p < 0.02). Three healthy women without arthritis or TB exposure had negative QFT-G TB. In vitro, all three tested positive every time for TB correlating to the dose of BiP or anti-BiP added, at 2 ug/ml, 5 ug/ml, 10 ug/ml, and 20 ug/ml. BiP naturally found in the majority of ACPA-positive RA patients can result in a false positive QFT-G TB. Subsequent undertreatment of RA, if biologic therapy is withheld, and overtreatment of presumed latent TB may harm patients.
28565837 Artesunate influences Th17/Treg lymphocyte balance by modulating Treg apoptosis and Th17 p 2017 May CD4(+) regulatory T (Treg) cells and T-helper 17 (Th17) cells have been shown to have important roles in rheumatoid arthritis (RA). In our previous study, it was demonstrated that artesunate was able to alter the Treg/Th17 ratio in patients with RA; however, the underlying mechanisms remain unclear. The present study established a male Sprague Dawley (SD) rat model of type II collagen-induced arthritis (CIA). SD rats were divided into normal control, CIA model and artesunate-treated (5, 10 or 20 mg/kg/day) groups. Treg and Th17 cells were detected in the synovium by immunohistochemical analysis of forkhead/winged helix transcription factor (Foxp3) and interleukin (IL)-17 expression. Subsequently, lymphocytes were extracted from the rat spleens, and the proportions of Treg/Th17 cells were detected by flow cytometry. The results demonstrated that the expression levels of Foxp3 were significantly decreased, and those of IL-17 were significantly increased, in the CIA model group, as compared with the normal control group. The results demonstrated that artesunate decreased the frequency of Th17 cells and increased the frequency of Treg cells in CIA rats in a dose-dependent manner. In conclusion, the present study suggested that artesunate may regulate the Th17/Treg balance by inducing Th17-mediated apoptosis. Therefore, artesunate may be considered a novel therapeutic agent for the treatment of patients with RA.
29138606 Mortality in Italian patients with rheumatoid arthritis: evidence for a low mortality rate 2017 OBJECTIVES: Mortality in patients with rheumatoid arthritis (RA) has never been investigated in Italy. This study is devoted to investigating all the distinct causes of mortality in Italian RA patients. METHODS: Clinical charts of patients consecutively admitted to an Italian tertiary center, from January 1, 2008 to December 31, 2014, were reviewed. Mortality rates (incidence mortality rate [IMR] and standardized mortality rate [SMR]) and causes of death as assessed at December 31, 2015, were registered. Mortality rates detected in our series were compared to those reported in other European cohorts and in the general Italian population. RESULTS: Six hundred and eight patients were observed for a median of 3.51 years. Overall IMR was 0.79 deaths/100 person-years. No significant difference between our IMR and that reported in Italian population by the National Institute of Statistics was observed. All-cause and neoplasm IMRs in our series were found to be significantly lower than that reported in the Norfolk Arthritis Registry, while no difference was detected in cardiovascular (CV) mortality. On the other hand, all causes and CV SMRs in our series were found to be higher than that reported in the general Italian population, while cancer and infectious SMRs were found to be lower. CONCLUSION: In our series, RA patients had an increased all-cause mortality, and in particular an increased death rate due to CV. However, a lower death rate due to cancer and infections was observed. This figure might be due to the careful follow-up of RA patients in tertiary centers, and the results underlines the need to improve the management of CV risk.
29900970 The Association of Anti-Aminoacyl-Transfer Ribonucleic Acid Synthetase Antibodies in Patie 2018 Mar OBJECTIVES: This study aims to analyze the distribution and clinicopathological characteristics of anti-aminoacyl-transfer ribonucleic acid (tRNA) synthetase (ARS) antibodies in rheumatoid arthritis patients. PATIENTS AND METHODS: We retrospectively studied the anti-ARS antibody levels in 228 RA patients' (44 males, 184 females; mean age 62.9±14.0 years; range 23 to 88 years) sera from their medical charts. We determined the association with anti-cyclic citrullinated peptide antibody levels, interstitial lung disease (ILD), rheumatoid factor, and methotrexate or biological disease modifying antirheumatic drug treatments. RESULTS: Anti-ARS antibodies were detected in 14 RA patients (6.1%). ILD complications were significantly higher among anti-ARS antibody-positive patients (57.1% vs 22.4%, p<0.05). Levels of anti-threonyl-tRNA-synthetase (anti-PL-7) and anti-alanyl-tRNA-synthetase (anti-PL-12), two anti-ARS antibodies, were higher in RA patients with concurrent ILD (both p<0.05). Myositis and ILD worsening were not observed in three anti-ARS antibody- positive patients despite biological disease modifying antirheumatic drug administration. There was no difference in anti-cyclic citrullinated peptide and rheumatoid factor specificities between patients with or without ARS antibodies. CONCLUSION: Anti-ARS antibodies were detected in RA patients, with higher prevalence in patients with concurrent ILD. RA patients, specifically those with ILD complications, should be tested for anti-ARS antibodies.
28494625 S100-alarmins: potential therapeutic targets for arthritis. 2017 Jul In arthritis, inflammatory processes are triggered by numerous factors that are released from joint tissues, promoting joint destruction and pathological progression. During inflammation, a novel family of pro-inflammatory molecules called alarmins is released, amplifying inflammation and joint damage. Areas covered: With regard to the role of the alarmins S100A8 and S100A9 in the pathogenesis of arthritis, recent advances and the future prospects in terms of therapeutic implications are considered. Expert opinion: There is still an urgent need for novel treatment strategies addressing the local mechanisms of joint inflammation and tissue destruction, offering promising therapeutic alternatives. S100A8 and S100A9, which are the most up-regulated alarmins during arthritis, are endogenous triggers of inflammation, defining these proteins as promising targets for local suppression of arthritis. In murine models, the blockade of S100A8/S100A9 ameliorates inflammatory processes, including arthritis, and there are several lines of evidence that S100-alarmins may already be targeted in therapeutic approaches in man.
28216754 Transfibular ankle arthrodesis: A novel method for ankle fusion - A short term retrospecti 2017 Jan BACKGROUND: Ankle arthrodesis has long been the traditional operative treatment for posttraumatic arthritis, rheumatoid arthritis, infection, neuromuscular conditions, and salvage of failed ankle arthroplasty. It remains the treatment of choice for patients in whom heavy and prolonged activity is anticipated. We present our short term followup study of functional outcome of patients who underwent transfibular ankle arthrodesis for arthritis of ankle due to various indications. MATERIALS AND METHODS: 29 transfibular ankle arthrodesis in 29 patients performed between April 2009 and April 2014 were included in this study. The mean age was 50 years (range 22-75 years). The outcome analysis with a minimum of 1-year postoperative followup were included. All the patients were assessed with the American Orthopaedic Foot and Ankle Society (AOFAS) Hindfoot scale. RESULTS: All cases of ankle fusions (100%) progressed to solid union in a mean postoperative duration of 3.8 months (range 3-6 months). All patients had sound arthrodesis. The mean followup period was 32.52 months (standard deviation ± 10.34). The mean AOFAS score was 74 (pain score = 32, functional score = 42). We found that twenty patients (68.96%) out of 29, had excellent results, 7 (24.13%) had good, and 2 (6.89%) showed fair results. CONCLUSION: Transfibular ankle arthrodesis is a simple and effective procedure for ankle arthritis. It achieves a high rate of union and good functional outcome on midterm followup.
28962195 Evaluation of destruction in a collagen-induced arthritis rat model: Bony spur formation. 2017 Sep Over the past 40 years, the collagen-induced arthritis (CIA) animal model has been widely used as a model of rheumatoid arthritis (RA). However, no model is able to completely depict the characteristics of cartilage destruction to date. In the later stage of joint cartilage destruction, bony spurs form in RA. This bony spur formation is an important symptom in the pathological development of RA. In the present study, CIA was used to elucidate the pathological process of bony spur formation. Joint damage and spur formation in the animal model was detected by radiology and histology. Radiology identified bony spurs in the knee and foot joints, which worsened as the disease progressed. Furthermore, following observations of histological sections, fusion and damage of the articular cartilage, as well as a higher number of osteoclasts, were identified. Previous results have determined that bony spurs may be involved in another pathological process that occurs during the later stages of RA. Therefore, further studies investigating this symptom are required to improve the understanding of RA and facilitate the development of an appropriate treatment for RA.
29354576 Long-Term Efficacy of Rehabilitation Following Arthroscopic Synovectomy in Patients With R 2017 Dec OBJECTIVE: To investigate the long-term efficacy of rehabilitation following arthroscopic synovectomy in patients with rheumatoid arthritis treated with biologic agents. METHODS: Arthroscopic synovectomy was performed in 29 joints of 17 patients, which were divided into two groups. Group 1 included arthroscopic synovectomy plus rehabilitation for 19 joints in 10 patients, and group 2 included arthroscopic synovectomy without rehabilitation for 10 joints in 7 patients. The Disease Activity Score C-reactive protein (DAS28-CRP), Health Assessment Questionnaire-Disability Index (HAQ-DI), and Functional Independence Measure (FIM) values (motor subscale) at 9.7 years after arthroscopic synovectomy were evaluated to identify the clinical factors related to outcomes. RESULTS: The increase in FIM score was significant in group 1 (p=0.05). HAQ-DI at 9 years was significantly decreased in group 1 (p=0.02). Therefore, arthroscopic synovectomy with rehabilitation was significant in improving FIM and HAQ-DI scores over a long period. Multiple regression analysis of FIM scores at 9 years indicated that rehabilitation (p=0.03) and disease duration (p=0.02) were significantly related to outcomes. FIM score at 9 years was significantly negatively correlated with disease duration (p=0.01, r=-0.58, Y=88.89-0.21X). CONCLUSION: Rehabilitation following arthroscopic synovectomy was effective in achieving high FIM scores over time in patients with rheumatoid arthritis.