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ID PMID Title PublicationDate abstract
24246048 Palmitoylethanolamide and luteolin ameliorate development of arthritis caused by injection 2013 INTRODUCTION: N-palmitoylethanolamine (PEA) is an endogenous fatty acid amide belonging to the family of the N-acylethanolamines (NAEs). Recently, several studies demonstrated that PEA is an important analgesic, antiinflammatory, and neuroprotective mediator. The aim of this study was to investigate the effect of co-ultramicronized PEA + luteolin formulation on the modulation of the inflammatory response in mice subjected to collagen-induced arthritis (CIA). METHODS: CIA was induced by an intradermally injection of 100 μl of the emulsion (containing 100 μg of bovine type II collagen (CII)) and complete Freund adjuvant (CFA) at the base of the tail. On day 21, a second injection of CII in CFA was administered. Mice subjected to CIA were administered PEA (10 mg/kg 10% ethanol, intraperitoneally (i.p.)) or co-ultramicronized PEA + luteolin (1 mg/kg, i.p.) every 24 hours, starting from day 25 to 35. RESULTS: Mice developed erosive hind-paw arthritis when immunized with CII in CFA. Macroscopic clinical evidence of CIA first appeared as periarticular erythema and edema in the hindpaws. The incidence of CIA was 100% by day 28 in the CII-challenged mice, and the severity of CIA progressed over a 35-day period with a resorption of bone. The histopathology of CIA included erosion of the cartilage at the joint. Treatment with PEA or PEA + luteolin ameliorated the clinical signs at days 26 to 35 and improved histologic status in the joint and paw. The degree of oxidative and nitrosative damage was significantly reduced in PEA + luteolin-treated mice, as indicated by nitrotyrosine and malondialdehyde (MDA) levels. Plasma levels of the proinflammatory cytokines and chemokines were significantly reduced by PEA + luteolin treatment. CONCLUSIONS: We demonstrated that PEA co-ultramicronized with luteolin exerts an antiinflammatory effect during chronic inflammation and ameliorates CIA.
23039206 Serum IFN-λ1 is abnormally elevated in rheumatoid arthritis patients. 2013 Feb Interferon (IFN)-λ1 is a newly described cytokine that is known for its proinflammatory activity in viral infection and in cancer. Because recent studies indicated that IFN-λ can influence significantly the innate and adaptive immune response, we studied IFN-λ in a prototypic systemic autoimmune disease, rheumatoid arthritis (RA). It was found that RA patients had higher mRNA levels in PBMC and higher serum levels of IFN-λ1 in comparison with healthy matched controls and ankylosing spondylitis (AS) patients. Although there was no correlation between serum IFN-λ1 and RA autoantibodies, RA patients that presented knee joint involvement displayed higher serum IFN-λ1 than patients without knee joint involvement, suggesting that abnormally elevated IFN-λ1 levels in RA can associate with knee joint disease.
24264528 [Phase IV non-interventional studies in the treatment of rheumatoid arthritis with biologi 2014 Feb BACKGROUND: In contrast to the restrictive nature of randomised controlled trials (RCT), non-interventional studies (NIS) investigate the features of a therapy in daily clinical practice. The observational plan of NIS does not dictate a treatment strategy, but is based on the product label. Unlike RCT, NIS therefore have no actual inclusion and exclusion criteria, allowing the study of broad heterogeneous patient populations. METHODS: NIS carried out in Germany with support from the pharmaceutical industry and investigating the use of biologics for the treatment of rheumatoid arthritis were identified and their findings were compared with those from the RCT of the respective biologic. RESULTS: Analysis of the identified NIS revealed the following: (1) populations in NIS were on average more than twice as large as in RCT, (2) patient characteristics in NIS and RCT were different, (3) the effectiveness of biologics in NIS was comparable to the efficacy observed in RCT, and (4) NIS collected supplementary data, e.g. on usage and dosing in clinical practice. CONCLUSION: NIS represent an important tool for the assessment of daily clinical practice. Despite methodological drawbacks, NIS provide valuable data that contribute to a more complete picture of the value of treatment with biologics. The English version of this article is available at SpringerLink (under "Supplemental").
24859782 Mycobacterium tuberculosis lipoarabinomannan antibodies are associated to rheumatoid arthr 2014 Dec Little is known regarding the environmental factors at play in igniting rheumatoid arthritis (RA) autoimmunity, although an association between Mycobacteria and RA has been documented. This pilot study focused on examining a possible involvement of Mycobacterium tuberculosis (MTB) and Mycobacterium avium ss. paratuberculosis (MAP) in RA. We measured out the serum levels of IgG antibody against different mycobacterial antigens in Sardinian patients and controls, by an enzyme-linked immunosorbent assay. The population study was composed of 61 RA patients under different therapies and 52 healthy controls, whereas the antigens tested were MTB lipoarabinomannan (ManLAM), MAP heath shock protein 70, and MAP protein tyrosine phosphatase. The frequencies of anti-ManLAM antibodies were higher in the RA group (23 %) compared to the healthy controls (5.7 %) (AUC = 0.7; p < 0.0001), whereas serum reactivity to MAP antigens was not observed. ManLAM antigen was also detected in the plasma of three RA patients (which were anti-ManLAM antibody positive) by Western blot analysis using anti-Man-LAM monoclonal antibodies. The data produced corroborate the hypothesis of a potential association between MTB ManLAM and RA disease, but so far, further studies are necessary to understand its role in RA pathogenesis.
23137648 The low binding affinity of ADAMTS4 for citrullinated fibronectin may contribute to the de 2013 Mar OBJECTIVES: Rapid cartilage degradation in the joints is observed in rheumatoid arthritis (RA). ADAMTS4 (a disintegrin and metalloproteinase with thrombospondin motifs-4) degrades aggrecan, the primary component of cartilage, therefore contributing to joint erosion in RA. The proteolytic activity of ADAMTS4 is inhibited by fibronectin (FN). FN is abundantly expressed in the synovia in RA and is modified by citrullination, the conversion of peptidylarginine to citrulline. This study aims to investigate the binding ability of citrullinated FN (cFN) to ADAMTS4 and the effect of cFN on aggrecanase activity. METHODS: The full-length recombinant ADAMTS4 was purified from HEK293 cells that were transiently transfected with a full-length cDNA coding for human ADAMTS4. A 40-kDa FN fragment exhibiting heparin binding was citrullinised with rabbit peptidylarginine deaminase. The binding activity of the full-length recombinant ADAMTS4 to cFN was investigated in an in vitro binding assay. The proteolytic activity of ADAMTS4 after incubation with cFN was determined using an aggrecanase activity kit, in which the ARGSVIL peptide is produced by digestion with aggrecanase. RESULTS: cFN displayed significantly decreased binding activity with ADAMTS4 compared with FN. The full-length ADAMTS4 produced large amounts of the ARGSVIL peptide, but the amount was markedly decreased in the presence of FN. The production of this peptide approached the normal level when the full-length ADAMTS4 was incubated with cFN. CONCLUSIONS: FN following citrullination is less effective in inhibiting the proteolytic activity of ADAMTS4. It is known that PADI4, an enzyme active in citrullination, is highly expressed in the synovial tissue in RA. Our results suggest that PADI4 in the RA synovium may contribute to cartilage destruction via the citrullination of FN.
23400887 Identification of citrullinated hsp90 isoforms as novel autoantigens in rheumatoid arthrit 2013 Apr OBJECTIVE: Subsets of patients with rheumatoid arthritis (RA) develop extraarticular complications that include interstitial lung disease (ILD). Because standardized algorithms for identification of RA patients at risk of developing clinically significant ILD are lacking, the purpose of this study was to elucidate unique serologic markers of RA-associated ILD (RA-ILD). METHODS: Sera from RA patients with ILD and from RA patients without ILD were used to immunoprecipitate citrullinated and uncitrullinated proteins derived from K562 cell extracts. Mass spectrometry was performed to facilitate identification of citrullinated proteins differentially immunoprecipitated by RA-ILD patient sera. These candidate proteins were then used as substrate antigens in custom enzyme-linked immunosorbent assays (ELISAs) for high-throughput screening of sera obtained from cohorts of patients with RA, RA-ILD mixed connective tissue disease (MCTD), or idiopathic pulmonary fibrosis (IPF). RESULTS: Differential immunoprecipitation and subsequent mass spectrometric sequencing identified citrullinated Hsp90α and citrullinated Hsp90β as candidate autoantigens in patients with RA-ILD. ELISAs incorporating uncitrullinated and citrullinated isoforms of Hsp90 as substrate antigens demonstrated that sera from patients with RA-ILD preferentially recognized citrullinated versions of Hsp90 with moderate sensitivity (range 20-30%) and great specificity (>95%) relative to sera derived from patients with RA alone (without ILD), patients with MCTD, or patients with IPF. CONCLUSION: These studies demonstrate the utility of a novel autoantigen discovery method based on differential immunoprecipitation of citrullinated protein extracts. Application of these techniques identified citrullinated versions of Hsp90α and Hsp90β as autoantibody targets distinguishing RA-ILD from RA without ILD, MCTD, and IPF, suggesting that anti-citrullinated Hsp90α/β autoantibodies may serve as effective biomarkers for the potentially devastating pulmonary manifestations of RA-ILD.
24382276 Perceptions of methotrexate use in rheumatoid arthritis by rheumatologists and their patie 2013 Dec AIM: To improve treatment for rheumatoid arthritis (RA), rheumatologists have embraced patient-reported outcomes; however, limited data are available on patient perceptions of treatment. Our objective was to assess the use and perceptions of methotrexate (MTX) by patients with RA (primary objective) and their rheumatologists, patient-reported adverse events (AEs) related to MTX, and patient-reported use of alcohol, folic acid and biologic agents. METHOD: Each rheumatologist completed a rheumatologist questionnaire and then asked patients with RA to complete a patient questionnaire. RESULTS: Questionnaires were completed by 46/50 rheumatologists and 1313/1313 patients. Patients (72% female, 38% > 10 years RA) took oral MTX regularly (72% never miss a dose) and at therapeutic doses. Most patients (79%) were currently taking MTX, but 36% of patients were on low doses (≤ 10 mg/week) and 8% intentionally and regularly did not take MTX. Most patients had a positive perception of MTX; 82% of patients considered MTX to be important; 60% preferred to continue taking MTX. Although AEs (generally mild and gastrointestinal) occurred regularly (38%) and in some patients continuously (13%), 41% of patients did not experience an AE. Patients abstained from alcohol (46%) and took folic acid (91%, but with variable dosage regimens and doses). There were 29% of patients taking biologic agent therapy; only 70% of these patients were also taking MTX. CONCLUSION: MTX was well used, well tolerated and well perceived. However, to ensure that MTX therapy is as effective as possible, rheumatologists should discuss MTX use with their patients and consider alternative strategies for some patients.
23548156 Implementation of the CDC translational informatics platform--from genetic variants to the 2013 Apr 2 BACKGROUND: Sequencing of the human genome and the subsequent analyses have produced immense volumes of data. The technological advances have opened new windows into genomics beyond the DNA sequence. In parallel, clinical practice generate large amounts of data. This represents an underused data source that has much greater potential in translational research than is currently realized. This research aims at implementing a translational medicine informatics platform to integrate clinical data (disease diagnosis, diseases activity and treatment) of Rheumatoid Arthritis (RA) patients from Karolinska University Hospital and their research database (biobanks, genotype variants and serology) at the Center for Molecular Medicine, Karolinska Institutet. METHODS: Requirements engineering methods were utilized to identify user requirements. Unified Modeling Language and data modeling methods were used to model the universe of discourse and data sources. Oracle11g were used as the database management system, and the clinical development center (CDC) was used as the application interface. Patient data were anonymized, and we employed authorization and security methods to protect the system. RESULTS: We developed a user requirement matrix, which provided a framework for evaluating three translation informatics systems. The implementation of the CDC successfully integrated biological research database (15172 DNA, serum and synovial samples, 1436 cell samples and 65 SNPs per patient) and clinical database (5652 clinical visit) for the cohort of 379 patients presents three profiles. Basic functionalities provided by the translational medicine platform are research data management, development of bioinformatics workflow and analysis, sub-cohort selection, and re-use of clinical data in research settings. Finally, the system allowed researchers to extract subsets of attributes from cohorts according to specific biological, clinical, or statistical features. CONCLUSIONS: Research and clinical database integration is a real challenge and a road-block in translational research. Through this research we addressed the challenges and demonstrated the usefulness of CDC. We adhered to ethical regulations pertaining to patient data, and we determined that the existing software solutions cannot meet the translational research needs at hand. We used RA as a test case since we have ample data on active and longitudinal cohort.
23852638 Rapid and sensitive analysis of euonine and wilforidine in human plasma by high-performanc 2013 Sep Euonine and wilforidine are biologically active Tripterygium wilfordii Hook. f. alkaloids. In this paper, a rapid and sensitive high-performance liquid chromatography-mass spectrometry (MS) method was developed and validated for the simultaneous determination of trace euonine and wilforidine in human plasma. An Oasis® mixed-mode cation-exchange polymeric sorbent was used for solid-phase extraction. The separation was carried out on a reversed-phase Zorbax Plus C18 column (50 mm × 2.1 mm, 1.8 μm) by using ammonium acetate (5 mmol/L)/acetonitrile (30/70, v/v) as the mobile phase at a flow rate of 0.7 mL/min. The quantification was carried out via ion trap MS in the positive selected ion monitoring mode using aconitine as an internal standard. Calibration curves showed good linearity ranging from 0.5 to 100.0 μg/L with correlation coefficient values >0.9990. The average recoveries of euonine and wilforidine ranged from 85.4 to 101.0% and 92.0 to 97.5%, respectively. The intra- and interday relative standard deviations were <8.7 and 12.9%, respectively. The limits of quantification for both euonine and wilforidine were 0.5 μg/L, which is suitable in the clinical pharmaceutical research of volunteer patients with rheumatoid arthritis.
24534758 Diagnostic delay in patients with rheumatoid arthritis, psoriatic arthritis and ankylosing 2015 Mar BACKGROUND/PURPOSE: Early diagnosis of inflammatory rheumatic diseases is important in order to improve long-term outcome. We studied whether delay in diagnosis (time between onset of symptoms and establishment of diagnosis) in patients with rheumatoid arthritis (RA), psoriatic arthritis (PSA) and ankylosing spondylitis (AS) changed from year 2000 to 2011. METHODS: Month and year of initial symptoms and diagnosis, gender, hospital, year of birth and date of first data entry were obtained for 13,721 patients with RA, PSA or AS who had been registered in the DANBIO registry. Time between symptom onset and diagnosis was modelled using generalised linear regression to predict the average duration for each calendar year of initial symptoms with adjustments for gender, year of birth and date of DANBIO entry. RESULTS: Patients with valid data (RA: 10,416 (73%); PSA: 1970 (68%); AS: 1335 (65%)) did not differ significantly from the whole DANBIO population, except more missing data in early years. The regression model showed that the mean duration from initial symptoms to diagnosis for RA, PSA and AS declined steadily from 30, 53 and 66 months (year 2000), respectively, to 3-4 months (year 2011). Sensitivity analyses including patients who were included after 2005, patients who had received biological treatment or had symptom onset less than 2 and 5 years prior to first entry into DANBIO showed similar results. CONCLUSION: Since the year 2000, a significant reduction in diagnostic delay was observed in this large cohort of patients with RA, PSA or AS, probably reflecting a stronger awareness of the importance of early diagnosis.
23905378 [Treating rheumatoid arthritis patients of Shen deficiency and cold invading syndrome by b 2013 May OBJECTIVE: To evaluate the clinical efficacy and safety of bushen quhan zhiwang decoction (BQZD) combined methotrexate (MTX) in treating rheumatoid arthritis (RA). METHODS: A prospective, randomized controlled study was carried out. RA patients of Shen deficiency and cold invading syndrome in the treatment group (120 cases) were treated with BQZD and MTX (10 mg/week), while those in the control group (120 cases) were treated with MTX (10 mg/week) alone. The therapeutic course for all was 24 weeks. The efficacy and safety indices were evaluated at the baseline and 24 weeks after treatment, including clinical signs and symptoms, condition assessment, Health Assessment Questionnaire (HAQ), disease activity index 28 (DAS28), laboratory parameters of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), safety indicators, and Chinese medical syndrome integrals. RESULTS: The total effective rate was 80. 0% in the treatment group, better than that of the control group (66.7%), showing statistical difference (P <0.01). In the two groups significant improvement of clinical signs and symptoms, ESR, CRP, visual analogue scale (VAS) by both physicians and patients, HAQ, DAS28, and Chinese medical syndrome integrals after treatment were shown (P <0.01). Better effects were obtained in the treatment group in lessening tender joint numbers and swollen joint numbers, VAS by both physicians and patients, DAS28, and Chinese medical syndrome integrals (P < 0.05). Besides, adverse reactions occurred less in the treatment group than in the control group (P < 0.05). CONCLUSIONS: BQZD had roles in relieving symptoms, improving joint functions, signs, ESR, and CRP. It was an effective herb for RA patients of Shen deficiency and cold invading syndrome. It could enhance the efficacy and reduce adverse reactions of MTX through synergistic effects with MTX.
24006307 Evaluation of therapeutic efficacy of Majoon Suranjan, a Unani formulation, in the treatme 2013 Dec Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder. Allopathic treatments for RA have various side-effects and limitations. Majoon Suranjan (MS) is a polyherbal Unani formulation used to treat RA. Although it is widely used, evidence-based toxicity and efficacy data are not available. The present study was designed to assess the safety and therapeutic efficacy of MS in experimental animals. Acute (14 days) and long-term (90 days) toxicity studies were carried out at three doses of MS, i.e. 440, 880 and 1760 mg/kg body weight in male and female Wistar rats. Arthritis was induced in male rats by immunization with bovine collagen type II and they were treated with vehicle, methotrexate (0.25 mg/kg body weight, intraperitoneal once weekly) and MS (880 mg/kg body weight, orally, daily) for 20 days. Serum rheumatoid factor, anticyclic citrullinated peptide antibody, antinuclear antibody and C-reactive protein (CRP) were estimated. None of the rats exhibited overt toxicity or mortality and MS was found to be safe at the tested doses. No abnormal findings were observed in haematological and biochemical parameters, necropsy and histopathology at therapeutic effective dose. MS significantly inhibited the footpad swelling in arthritic rats while serum autoantibodies and CRP levels were significantly decreased. The present study demonstrates that at therapeutic doses, the Unani medicine, MS is relatively safe. Furthermore, MS was found to be effective in decreasing the biomarkers of RA, thus providing scientific evidence in support of its traditional use in the treatment of RA.
23611369 Regional differences regarding risk of developing rheumatoid arthritis in Stockholm County 2013 OBJECTIVES: Rheumatoid arthritis (RA) is a complex disease that is associated with genetic and environmental factors. We have investigated geospatial variation in the risk of developing RA within Stockholm County, Sweden, with respect to established environmental risk factors for RA, as well as serologically defined subgroups of RA. METHOD: Information regarding geographical location for 1432 cases and 2529 controls from the Epidemiological Investigation of Rheumatoid Arthritis (EIRA) study, living in Stockholm County at RA symptom onset, or matched date for controls, was used to estimate geospatial variation in risk. We used generalized additive models (GAMs) to create a risk surface, calculate odds ratios (ORs), and adjust for potential confounding by smoking, education level, and RA within family. We performed a stratified analysis based on the presence/absence of anti-citrullinated peptide antibodies (ACPA). RESULTS: We found significant spatial variation in the odds of developing RA in Stockholm County. After adjustment for smoking, education level, and family history of RA, this geospatial variation remained. The stratified analysis showed areas with higher ORs for ACPA-positive RA and ACPA-negative RA, after adjusting for smoking, education level, and having a family history of RA. Living in the city of Stockholm was associated with decreased risk of RA. CONCLUSIONS: The risk of developing RA in Stockholm County is not distributed evenly and there are areas of increased risk that could not be explained by known factors. Further investigations of local exposures or social factors are warranted.
24084414 Inflammatory arthritis. The role of physical and rehabilitation medicine physicians. The E 2013 Aug One of the objectives of the Professional Practice Committee (PPC) of the Physical and Rehabilitation Medicine (PRM) Section of the Union of European Medical Specialists (UEMS) is the development of the field of competence of PRM physicians in Europe. To achieve this objective, UEMS PRM Section PPC has adopted a systematic action plan of preparing a series of papers describing the role of PRM physicians in a number of disabling health conditions, based on the evidence of effectiveness of the physical and rehabilitation medicine interventions. Inflammatory arthritis is a major cause of disability with an important economic burden in society. The goals in the management of inflammatory arthritis are to control pain and disease activity, prevent joint damage, protect and enhance function and improve quality of life. This paper aims to define the role of PRM physicians in people with inflammatory arthritis. PRM interventions imply non-pharmacological treatments which include patient education for joint protection, energy conservation and self-management techniques, exercise therapy, physical modalities, orthoses/assistive devices and balneotherapy. Therapeutic patient education and exercises are the cornerstones of therapy with strong evidence of their effectiveness to improve function. Physical modalities are primarily used to decrease pain and stiffness whereas orthoses/assistive devices are usually prescribed to enhance activities and participation. PRM physicians have distinct roles in the management of people with inflammatory arthritis such that they effectively organise and supervise the PRM program in the context of interdisciplinary team work. Their role starts with a comprehensive assessment of patient's functioning based on the International Classification of Functioning Disability and Health (ICF) as the framework. In the light of this assessment, appropriate PRM interventions individualised for the patient are administered. Future research and actions regarding the role of PRM in inflammatory arthritis should target access to care, updates on the use and effectiveness of physical modalities, orthoses/assistive devices, and standardization of therapeutic patient education programs.
25193807 Bone resorption correlates with the frequency of CD5⁺ B cells in the blood of patients w 2015 Mar OBJECTIVE: The prevention of bone resorption and subsequent joint destruction is one of the main challenges in the treatment of patients suffering from RA. Various mechanisms have previously been described that contribute to bone resorption in tightly defined cohorts. Here we analysed a cross-sectional cohort of RA patients and searched for humoral and cellular markers in the peripheral blood associated with bone resorption. METHODS: We enrolled 61 consecutive RA patients positive for ACPA. Blood was analysed by flow cytometry to determine the percentages of regulatory T cells and B cell subpopulations. Cytokine (TNF-α, IL-6, IL-10) and ACPA levels as well as the bone resorption marker CTX-1 were determined from the patients' sera. Standard clinical disease parameters were included. RESULTS: Multivariate analyses showed that the percentages of CD5(+) B cells were positively correlated with CTX-1 serum levels. However, neither low-avidity ACPA nor serum IL-6 levels, both known to be produced by CD5(+) cells, were associated with CTX-1 in patients' sera. There was no correlation between CTX-1 levels and clinical parameters or ACPA levels. CONCLUSION: In summary, we found that the CD5(+) B cell population is associated with bone resorption as measured via serum CTX-1 levels in a cross-sectional cohort of RA patients. However, a possible functional link between CD5(+) B cells and bone resorption still needs to be defined.
23819215 [Effects of moxibustion intervention on inflammatory reactions and expression of suppresso 2013 Apr OBJECTIVE: To observe the effect of moxibustion intervention on inflammatory reactions and expression of suppressor of cyfokine signaling 1 (SOCS 1) and SOCS 2 [Which are involved in inhibition of the Janus Kinase-signal transducer and activator of transcrip-tion (JAK/STAT signaling pathway and in sffenuation of cytokine signaling)] in synovium cells of the hind-knee joint in rheumatoid arthritis (RA) rabbits, so as to study its mechanism underlying improvement of RA. METHODS: Forty-two Japanese big-ear white rabbits were randomized into control, model and moxibustion groups respectively, with 14 cases in each group. RA model was established by injection of Freund's Complete Adjuvant (0. 5 mL/kg) into the rabbits' bilateral hind-knee joint cavities. Moxibustion was applied to bilateral "Shenshu" (BL 23) areas, 5 cones every time, once daily for 3 weeks except the Sundays. The perimeters of rabbits' hind legs were measured before and after modeling and after the therapy. The synovial tissue of joint was sampled for analyzing the expression levels of SOCS 1 and SOCS 3 by immunohistochemistry. RESULTS: Before the therapy, the perimeters of bilateral knee joints of the control, model and moxibustion groups were of no statistical significance (P>0. 05). In comparison with the control group, the perimeters of bilateral knee joints were significantly increased on day 1, 7, 14 and 21 in the model group (P<0. 01). Compared with the model group, the perimeters of bilateral knee joints in the moxibustion group were significantly decreased (P<0. 05), suggesting an improvement of the inflammatory reaction after moxibustion intervention. Correspondingly, synovial SOCS 1 and SOCS 3 expression levels were remarkabely higher in the model group than in the control group (P<0. 01), and obviously decreased in the moxibustion group compared with the model group (P<0. 01). CONCLUSIONS: Moxibustion intervention has an anti-inflammatory and detumescent effects in RA rabbits, which may be closely associated with its effects in down-regulating expression of SOCS 1 and SOCS 3 proteins by suppressing negative feedback regulatory JAK/STAT pathway in synovial cells. [KEY WORDS] Moxibustion; Rheumatoid arthritis; Inflammatory reactions; Synovial cells; Suppressor of cytokine signaling proteins; Negative-feedback regulatory factors
23460159 Diagnosis and treatment of connective tissue disease-associated interstitial lung disease. 2013 Mar Interstitial lung disease (ILD) is one of the most serious pulmonary complications associated with connective tissue diseases (CTDs), resulting in significant morbidity and mortality. Although the various CTDs associated with ILD often are considered together because of their shared autoimmune nature, there are substantial differences in the clinical presentations and management of ILD in each specific CTD. This heterogeneity and the cross-disciplinary nature of care have complicated the conduct of prospective multicenter treatment trials and hindered our understanding of the development of ILD in patients with CTD. In this update, we present new information regarding the diagnosis and treatment of patients with ILD secondary to systemic sclerosis, rheumatoid arthritis, dermatomyositis and polymyositis, and Sjögren syndrome. We review information on risk factors for the development of ILD in the setting of CTD. Diagnostic criteria for CTD are presented as well as elements of the clinical evaluation that increase suspicion for CTD-ILD. We review the use of medications in the treatment of CTD-ILD. Although a large, randomized study has examined the impact of immunosuppressive therapy for ILD secondary to systemic sclerosis, additional studies are needed to determine optimal treatment strategies for each distinct form of CTD-ILD. Finally, we review new information regarding the subgroup of patients with ILD who meet some, but not all, diagnostic criteria for a CTD. A careful and systematic approach to diagnosis in patients with ILD may reveal an unrecognized CTD or evidence of autoimmunity in those previously believed to have idiopathic ILD.
23650618 Roles of adipocytes and fibroblasts in activation of the alternative pathway of complement 2013 Jun 15 The complement system is involved in mediation of joint damage in rheumatoid arthritis, with evidence suggesting activation of both the classical and alternative pathway (AP). The AP is both necessary and sufficient to mediate collagen Ab-induced arthritis, an experimental animal model of immune complex-induced joint disease. The AP in mice is dependent on MASP-1/3 cleavage of pro-factor D (pro-FD) into mature factor D (FD). The objectives of the current study were to determine the cells synthesizing MASP-1/3 and pro-FD in synovial tissue. Collagen Ab-induced arthritis was studied in wild-type C57BL/6 mice, and the localization of mRNA and protein for FD and MASP-1/3 in synovial adipose tissue (SAT) and fibroblast-like synoviocytes (FLS) was determined using various techniques, including laser capture microdissection. SAT was the sole source of mRNA for pro-FD. Cultured differentiated 3T3 adipocytes, a surrogate for SAT, produced pro-FD but no mature FD. FLS were the main source of MASP-1/3 mRNA and protein. Using cartilage microparticles (CMPs) coated with anti-collagen mAb and serum from MASP-1/3(-/-) mice as a source of factor B, pro-FD in 3T3 supernatants was cleaved into mature FD by MASP-1/3 in FLS supernatants. The mature FD was eluted from the CMP, and was not present in the supernatants from the incubation with CMP, indicating that cleavage of pro-FD into mature FD by MASP-1 occurred on the CMP. These results demonstrate that pathogenic activation of the AP can occur in the joint through immune complexes adherent to cartilage and the local production of necessary AP proteins by adipocytes and FLS.
24504797 Increased risk of complications following total joint arthroplasty in patients with rheuma 2014 Feb OBJECTIVE: Most of the evidence regarding complications following total hip arthroplasty (THA) and total knee arthroplasty (TKA) are based on patients with osteoarthritis (OA); less is known about outcomes in rheumatoid arthritis (RA). Using a validated algorithm for identifying patients with RA, we undertook this study to compare the rates of complications among THA and TKA recipients between those with RA and those without RA. METHODS: In patients who underwent a first primary elective THA or TKA between 2002 and 2009, those with RA were identified using a validated algorithm: a hospitalization with a diagnosis code for RA or 3 physician billing claims with a diagnosis code for RA, with at least 1 claim by a specialist (rheumatologist, orthopedic surgeon, or internist) in a 2-year period. Recipients with diagnostic codes suggesting an inflammatory arthritis, but not meeting RA criteria, were classified as having inflammatory arthritis. All remaining patients were deemed to have OA. Cox proportional hazards models, censored on death, were used to determine the relationship between the type of arthritis and the occurrence of specific complications, adjusting for potential confounders (age, sex, comorbidity, and provider volume). RESULTS: We identified 43,997 eligible THA recipients (3% with RA) and 71,793 eligible TKA recipients (4% with RA). Total joint arthroplasty recipients with RA had higher age and sex-standardized rates of dislocation following THA (2.45%, compared with 1.21% for recipients with OA) and higher age and sex-standardized rates of infection following TKA (1.26%, compared with 0.84% for recipients with OA). Controlling for potential confounders, recipients with RA remained at increased risk of dislocation within 2 years of THA (adjusted hazard ratio [HR] 1.91, P = 0.001) and remained at increased risk of infection within 2 years of TKA (adjusted HR 1.47, P = 0.03) relative to recipients with OA. CONCLUSION: Patients with RA are at higher risk of dislocation following THA and are at higher risk of infection following TKA relative to those with OA. Further research is warranted to elucidate explanations for these findings, including the roles of medication profile, implant choice, postoperative antibiotic protocol, and method of rehabilitation following joint replacement.
24241035 Physician global assessment at 3 months is strongly predictive of remission at 12 months i 2014 Mar OBJECTIVE: The objective of this study was to determine predictors of 1-year remission in early RA (ERA) using baseline and 3-month data. METHODS: The Canadian Early Arthritis Cohort (CATCH) patients were included if baseline, 3- and 12-month data were available. Regression analyses for four different definitions of remission at 12 months were done to determine baseline and 3-month predictors of remission. RESULTS: Five hundred and sixty-two patients had complete data at 12 months (mean age 53.4 years, disease duration 6.2 years, 73% female). The factors at baseline associated with all four remission outcomes at 12 months were age, gender, income, education, tender joint count (TJC), patient global assessment (PtGA), HAQ and pain. Baseline ESR was associated with the 28-joint DAS (DAS28) remission only. At 3 months, all four remission definitions were associated with TJC, swollen joint count, physician global assessment (PGA), PtGA, HAQ, pain, ESR and CRP in univariate analyses. In the regression model, variables associated with Simple Disease Activity Index remission were PGA [odds ratio (OR) 0.77, P < 0.001), pain (OR 0.85, P = 0.004), age (OR 0.98, P = 0.006) and HAQ (OR 0.49, P = 0.011); Clinical Disease Activity Index remission was associated with PGA (OR 0.77, P < 0.001), pain (OR 0.85, P = 0.003), age (OR 0.98, P = 0.015) and CRP (OR 0.80, P = 0.031). DAS28 remission was predicted by ESR (OR 0.95, P < 0.001), PGA (OR 0.76, P < 0.001), age (OR 0.98, P = 0.001), HAQ (OR 0.57, P = 0.006) and male gender (OR 2.01, P = 0.005), whereas Boolean remission was associated with pain (OR 0.79, P = 0.009), age (OR 0.98, P = 0.016), PtGA (OR 0.83, P = 0.025) and PGA (OR 0.86, P = 0.038). CONCLUSION: A low PGA at 3 months was consistently associated with 1-year remission in ERA.