Browse

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

ID PMID Title PublicationDate abstract
28713386 Impairment of Granzyme B-Producing Regulatory B Cells Correlates with Exacerbated Rheumato 2017 Hyperactivated B cells have been demonstrated the contribution to the development of rheumatoid arthritis (RA). While the recognition of the negative regulatory function of B cells further promoted our understanding of their pathogenic role in RA. Recently, a new population of granzyme B (GrB)-producing B cells was identified, which was proved to be involved in cancer and infectious diseases. However, their characteristics and roles in RA remain to be elucidated. In the present study, we aim to further characterize whether B cells could produce GrB and reveal their potential role in the pathogenesis of RA. Here, we further demonstrated peripheral blood B cells from healthy individuals could produce and secrete GrB, which could be enhanced by IL-21 and/or anti-B-cell receptor stimulation. These cells could negatively regulate Th1 and Th17 cells partly via downregulating TCR zeta chain and inducing T cell apoptosis, which might be termed as GrB-producing regulatory B cells (Bregs). These GrB-producing Bregs were significantly decreased under RA circumstance concomitant of lower levels of IL-21 receptor, with impaired regulatory functions on Th1 and Th17 cells. Moreover, the frequencies of these cells were negatively correlated with RA patient disease activity and clinical features. After effective therapy with disease remission in RA, these GrB-producing Bregs could be recovered. Therefore, our data revealed that B cells could produce GrB with immunosuppressive functions, and the impairment of this Breg subset was correlated with RA pathogenesis.
28638677 Changes in sirtuin 2 and sirtuin 3 mRNA expressions in rheumatoid arthritis. 2017 Jun OBJECTIVE: Sirtuins (SIRTs) play a prominent role in metabolism, apoptosis, aging, inflammation, and epigenetics. Inflammation, apoptosis, and epigenetics are pathogenic issues in rheumatoid arthritis (RA). This study aimed to evaluate SIRT2 and SIRT3 mRNA expressions in patients with RA. MATERIAL AND METHODS: Fifty-four patients with RA and 26 healthy controls were enrolled. Disease activity was determined using the disease activity score (DAS) 28-erythrocyte sedimentation rate (ESR) (score of >2.6 was considered to be active). SIRT2 and SIRT3 mRNA expressions in the extracellular plasma were investigated by real-time PCR. RESULTS: SIRT3 mRNA expression was higher in the RA group than in the healthy control group (4.64 fold, p<0.001), whereas SIRT2 mRNA expression was relatively lower in the RA group than in the healthy control group (0.55 fold, p=0.109). However, SIRT2 (1.73 fold, p=0.065) and SIRT3 (3.58 fold, p=0.051) mRNA expressions were relatively higher in patients with active RA than in those with inactive RA. CONCLUSION: In RA, SIRT3 mRNA expression is increased, whereas SIRT2 mRNA expression is decreased. Conversely, SIRT2 and SIRT3 mRNA expressions increase in active RA. Therefore, the fate of each SIRT may differ in RA.
28553419 The Use of patient Reported Outcome Measures for Rheumatoid Arthritis in Japan: A Systemat 2017 BACKGROUND: Patient-reported outcomes (PRO) obtained through routine medical care may identify patients' day-to-day burden and help tackle the disease from the patients' perspective. However, there is a paucity of information regarding the availability of PRO data and PRO tools for rheumatoid arthritis (RA) in Japan. OBJECTIVE: We reviewed the literature on PRO data availability and to identify PRO measures implemented in Japan for RA patients. METHOD: We conducted a systematic literature review using ICHUSHI and the PubMed databases on PRO measures for RA published from January 2011 to August 2015 in Japan. RESULTS: After removing duplicates, 2423 manuscripts were found. From these, 100 manuscripts were included for review and analysis. We found 29 PRO tools that were used to assess various domains of health such as general well-being, pain, functionality, and fatigue. More than 90% of the studies utilized PRO tools for research purpose. Only one study reported PRO tool implementation in the routine medical care. CONCLUSION: The importance of PROs is recognized in Japan. PRO tools varied significantly and were mostly used for research purposes, while reports on the use of PRO measures in routine medical care were limited. Despite the awareness of PROs in the research community, unmet needs remain among RA patients in Japan. Further work is needed to investigate ways in which PROs can better reflect these unmet needs and be utilized in routine medical care.
29467860 Roles of microRNA-539 and osteopontin in rheumatoid arthritis. 2018 Mar The present study aimed to investigate the role and mechanism of microRNA-539 (miR-539) in rheumatoid arthritis (RA). A total of 68 RA patients and 46 osteoarthritis patients were enrolled into the current study. Peripheral blood and joint fluid were collected prior to treatment. Reverse transcription-quantitative polymerase chain reaction was performed to detect osteopontin (OPN) mRNA and miR-539 expression levels, while ELISA and western blot analysis were applied to detect OPN protein expression. In addition, bioinformatics analysis predicted that miR-539 directly targeted OPN, while dual-luciferase assay was used to validate this finding. Furthermore, agomiR-539 transfection and OPN knockdown by siRNA were conducted in MH7A cells, and MTT assay was used to detect MH7A cell proliferation. The results indicated that OPN was significantly increased in the blood and joint fluid of RA patients, while miR-539 expression was significantly decreased in the two types of specimens (P<0.05). Subsequent to silencing OPN by siRNA, the proliferation of MH7A cells was decreased (P<0.05). Following upregulation of miR-539, OPN expression was significantly decreased and cell proliferation was inhibited. Dual-luciferase assay revealed that miR-539 regulated OPN expression through complementary binding to 3'-untranslated region. OPN was also significantly increased in the blood and joint fluid of RA patients, which may be associated with the downregulation of miR-539. Thus, miR-539 may promote the development and progression of RA through regulating OPN.
29177079 Effect of Fcγ-receptor 3a (FCGR3A) gene polymorphisms on rituximab therapy in Hungarian p 2017 BACKGROUND: Rheumatoid arthritis (RA) treatment includes the use of the anti-CD20 monoclonal antibody rituximab (RTX). RTX acts through Fcγ-receptors (FCGR) on effector natural killer cells and macrophages and it can be administered effectively in RA and in lymphomas. Based on the results of in vitro experiments, its efficacy may depend of FCGR gene polymorphisms in both diseases. AIM: As genetic background of diseases and therapeutic efficacy (pharmacogenetics) may vary among different geographical regions, we wished to assess possible relationships between FCGR3A polymorphism and the therapeutic outcome of RTX therapy in a Hungarian RA cohort. PATIENTS AND METHODS: Altogether, 52 patients, 6 men and 46 women, were included in the study. Peripheral blood samples were used to determine FCGR3A polymorphism by genotyping using real-time PCR method. RESULTS: The distribution of FCGR3A genotypes was 8 VV, 34 VF and 10 FF. Disease activity score 28 (DAS28) reductions in patients with VV, VF and FF genotypes were 1.98±0.54 (p=0.008 between DAS28 before and after treatment), 2.07±0.23 (p<0.001) and 1.59±0.52 (p=0.014), respectively. Significant differences in DAS28 reductions on treatment were found between VF heterozygotes and FF homozygotes (p=0.032), as well as between heterozygotes and all (VV+FF) homozygotes (p=0.017). Furthermore, significantly more VV (62.5%; p=0.030) and VF (64.7%; p=0.015) patients achieved low disease activity compared with FF subjects (30.0%). CONCLUSION: Our results suggest that FCGR3A polymorphism may predict more effective disease activity reduction by RTX. Furthermore, carrying the V allele may also be associated with better therapeutic response in Hungarian patients with RA.
29118859 Pleuropulmonary manifestation in patients with rheumatoid arthritis in Saudi Arabia. 2017 Oct BACKGROUND AND OBJECTIVES: Pleuropulmonary (PP) involvement in rheumatoid arthritis (RA) is associated with high morbidity and mortality. Nevertheless, limited data are available regarding lung complications in the Middle East, especially in Saudi Arabia. The objectives of the current study were to determine the prevalence of PP manifestations and to identify the associated risk factors. METHODS: This was a retrospective study involving 419 patients diagnosed at a tertiary center over a 12.5-year period. The frequency of pulmonary manifestations was recorded based on combined results from chest X-rays, pulmonary function tests, and high-resolution computed tomography scan of the chest. RESULTS: The overall frequency of lung involvement was 25.8%. Pneumonia, bronchiectasis, and interstitial lung disease were the most common abnormalities (36%, 35%, and 23%, respectively). The presence of comorbid illness (odds ratio [OR]: 3.19; 95% confidence interval [CI]: 2.02-5.1), male gender (OR: 2.4; 95% CI: 1.3-4.24), and the presence of extra-articular manifestations of RA (ExRA) (OR: 2.35; 95% CI: 0.4-4.01) were predictive of lung involvement. CONCLUSIONS: Pneumonia, bronchiectasis, and interstitial lung disease were the most common abnormalities seen in RA patients. The presence of comorbidity, male gender, and ExRA was significantly associated with lung involvement.
28508282 Malignancy Incidence, Management, and Prevention in Patients with Rheumatoid Arthritis. 2017 Dec Traditional and biologic disease-modifying antirheumatic drugs (DMARDs) are effective medications for the management of rheumatoid arthritis (RA). However, the effects of these medications on immune function raises concern that they may increase long-term cancer risk. The baseline risk for some cancers appears to differ in patients with RA compared to the general population, with the former having an increased risk of lymphoma, lung cancer and renal cancer, but a decreased risk of colorectal and breast cancer. Some DMARDs appear to increase the rate of specific cancer types (such as bladder cancer with cyclophosphamide), but few appear to increase the overall cancer risk. Studying the link between lymphoma and disease severity in RA is complicated because patients with persistently active disease are at increased risk for lymphoma, and disease severity correlates with more intense use of immunosuppressive medications. Overall, cancer risk in patients with RA is slightly above that of the general population, with the increased risk likely secondary to an increased risk of lymphomas in those with high disease activity. Risk mitigation includes management of RA disease activity as well as age- and sex-appropriate cancer screening.
28326188 Physical workload is associated with increased risk of rheumatoid arthritis: results from 2017 OBJECTIVES: This study investigated: (1) the association of physical workload (PW) and risk of rheumatoid arthritis (RA); (2) the potential interactions between PW and the genes in the human leucocyte antigen (HLA) region. METHODS: A population-based case-control study involving incident cases of RA (3150 cases and 5130 controls) was performed using data from the Swedish Epidemiological Investigation of Rheumatoid Arthritis. Information on 7 types of self-reported PW exposure and HLA-DRB1 genotypes of cases and controls were gathered. Anticitrullinated protein antibody (ACPA) status of cases was identified. For each PW exposures, exposed participants were compared with unexposed participants. ORs with 95% CIs of RA (overall), ACPA-positive RA and ACPA-negative RA associated with different PWs were estimated using logistic regression. HLA-PW interactions were estimated using the principle of departure from additivity of effects by calculating attributable proportion (AP) due to interaction. RESULTS: ORs of developing RA associated with 6 various PW exposures ranging from 1.3 (95% CI 1.1 to 1.4) to 1.8 (95% CI 1.6 to 2.0) were observed. Exposure to more types of PW was associated with increasing risk for RA (p<0.0001). No major difference in the ORs between ACPA-positive and ACPA-negative RA was found. For some exposures, we found evidence of interactions between PW and the HLA-DRB1 shared epitope genes, regarding risk of ACPA-positive RA (AP: from 0.3 (95% CI 0.1 to 0.5) to 0.4 (95% CI 0.2 to 0.6)). CONCLUSIONS: PW is associated with the risk of ACPA-positive and ACPA-negative RA. Interactions between PW and the HLA-DRB1 shared epitope were found in ACPA-positive RA.
28149185 Promoter polymorphism (-590, T/C) of interleukin 4 (IL4) gene is associated with rheumatoi 2017 Feb Rheumatoid arthritis (RA) is a chronic disease. It causes chronic inflammation of the joint. Recent studies suggested that interleukin 4 (IL4) contributes to susceptibility and severity of rheumatoid arthritis (RA). Especially, it was reported that promoter polymorphism (-590, T/C) of IL4 gene has been associated with susceptibility of RA. The aim of present study was to investigate whether the promoter polymorphism (-590, T/C) of IL4 gene is associated with the susceptibility of RA using meta-analysis. And in order to perform meta-analysis, comprehensive meta analysis program was used. Genetic models (co-dominant, dominant, recessive, and allele) were used to determine odds ratios (ORs), 95% confidence intervals (CIs), and P values. Nine case-control studies with case and control design were included in this meta-analysis. Overall, meta-analysis revealed a strong association with susceptibility of RA [OR = 1.303, 95% CI = 1.093-1.554, P = 0.003 in allele model (C vs. T); OR = 1.247, 95% CI = 1.054-1.474, P = 0.010 in dominant model (CC vs. CT + TT); OR = 2.148, 95% CI = 1.263-3.651, P = 0.005 in recessive model (CC + CT vs. TT)]. Our data demonstrated that promoter polymorphism (-590, T/C) of IL4 gene may be contributed to susceptibility of RA. However, more studies with a larger sample size are needed to provide more precise evidence.
29156638 Development of Evidence-Based Disease Education Literature for Pakistani Rheumatoid Arthri 2017 Nov 20 Rheumatoid arthritis affects 0.5% to 1% of the population globally and is one of the most common causes of disability. Patient education plays a key role in improving treatment outcomes. The purpose of this study was to discuss the process involved in designing an evidence-based disease education literature for rheumatoid arthritis patients of Pakistan in Urdu language with culturally relevant illustrations. A study was conducted to develop disease education literature using Delphi consensus, content validity, and patient feedback. A panel of experts comprised of university professors and health care experts, including health practitioners and pharmacists as well as a social scientist, was set up to assess the need. Eight patients were randomly selected and were asked to give their feedback. Their feedback was incorporated in the development process. The entire process was carried out in eight steps. A disease education literature for patients of rheumatoid arthritis was developed and edited in the form of a booklet. The booklet contained evidence-based information that must be provided to patients in both Urdu and English languages with culturally relevant illustrations. The availability of such literature is significant, as it enables the patients to seek knowledge at home at their convenience. This home-based knowledge support is as helpful as any other means of medical care. The developed literature is planned to be used in further studies which will evaluate its impact in improving knowledge of RA patients.
29062314 Harnessing Apoptotic Cell Clearance to Treat Autoimmune Arthritis. 2017 Early-stage apoptotic cells possess immunomodulatory properties. Proper apoptotic cell clearance during homeostasis has been shown to limit subsequent immune responses. Based on these observations, early-stage apoptotic cell infusion has been used to prevent unwanted inflammatory responses in different experimental models of autoimmune diseases or transplantation. Moreover, this approach has been shown to be feasible without any toxicity in patients undergoing allogeneic hematopoietic cell transplantation to prevent graft-versus-host disease. However, whether early-stage apoptotic cell infusion can be used to treat ongoing inflammatory disorders has not been reported extensively. Recently, we have provided evidence that early-stage apoptotic cell infusion is able to control, at least transiently, ongoing collagen-induced arthritis. This beneficial therapeutic effect is associated with the modulation of antigen-presenting cell functions mainly of macrophages and plasmacytoid dendritic cells, as well as the induction of collagen-specific regulatory CD4(+) T cells (Treg). Furthermore, the efficacy of this approach is not altered by the association with two standard treatments of rheumatoid arthritis (RA), methotrexate and tumor necrosis factor (TNF) inhibition. Here, in the light of these observations and recent data of the literature, we discuss the mechanisms of early-stage apoptotic cell infusion and how this therapeutic approach can be transposed to patients with RA.
28420491 Telemedicine for patients with rheumatic diseases: Systematic review and proposal for rese 2017 Aug OBJECTIVE: To systematically review the scientific literature regarding tele-rheumatology and draw conclusions about feasibility, effectiveness, and patient satisfaction. METHODS: PubMed, Scopus, and Cochrane database searches were performed (April 2016) using relevant MeSH and keyword terms for telemedicine and rheumatic diseases. Articles were selected if reporting outcomes for feasibility, effectiveness, and patient satisfaction and methodologically appraised using the Cochrane Collaboration's tool for assessing risk of bias and a modified version of CONSORT 2010 Statement. RESULTS: A total of 177 articles were screened, 23 were selected for the present review but only 9 were RCTs. Five studies reported on feasibility, 14 effectiveness, and 9 satisfaction rates for different tele-rheumatology interventions grouped in synchronous (remotely delivered consultation) and asynchronous (remote disease activity assessment; tele-monitoring of treatment strategies or rehabilitation; and remotely delivered self-management programs). Seven studies (30.4%) were on rheumatoid arthritis, 2 (8.7%) were on systemic sclerosis (1 including also rheumatoid arthritis patients), 5 (21.7%) on fibromyalgia, 2 (8.7%) on osteoarthritis, 3 (13.0%) on juvenile idiopathic arthritis and 4 (17.4%) on mixed disease cohorts. Interventions and outcomes heterogeneity prevented meta-analysis of results. Overall, feasibility and patient satisfaction rates were high or very high across intervention types. Effectiveness was equal or higher than standard face-to-face approach in controlled trials which, however, were affected by small sample size and lack of blinding participants according to appraisal tools. CONCLUSION: Telemedicine may provide a well-accepted way to remotely deliver consultation, treatment and monitoring disease activity in rheumatology. Higher quality RCTs demonstrating effectiveness of different tele-rheumatology interventions are needed.
28286682 Rheumatoid Meningitis Occurring during Etanercept Treatment. 2017 We report a 65-year-old man who had repetitive seizures 6 months after receiving etanercept, methotrexate, and prednisolone for rheumatoid arthritis. Mononuclear cells were mildly increased in the cerebrospinal fluid (CSF). Brain magnetic resonance imaging (MRI) showed high intensity along sulci of the frontal and parietal lobes. Brain biopsy revealed lymphocyte and plasma cell infiltration in the meninges, confirming the diagnosis of rheumatoid meningitis. After steroid pulse therapy, seizures resolved and clinical findings improved. When etanercept was replaced by tocilizumab, rheumatoid meningitis did not recur. Although TNF-α inhibitors can control joint symptoms of rheumatoid arthritis, they may induce rheumatoid meningitis.
27160252 APL-1, an altered peptide ligand derived from heat-shock protein, alone or combined with m 2017 May Induction of tolerance to autoantigens in vivo is a complex process that involves several mechanisms such as the induction of regulatory T cells and changes in the cytokine and chemokine profiles. This approach represents an attractive alternative for treatment of autoimmune diseases. APL-1 is an altered peptide ligand derived from a novel CD4 + T cell epitope of human heat-shock protein of 60 kDa (HSP60), an autoantigen involved in the pathogenesis of rheumatoid arthritis (RA). We have shown previously that this peptide efficiently inhibited the course of adjuvant-induced arthritis in Lewis rats and induced regulatory T cell (Treg) in ex vivo assay with PBMC isolated from RA patients. This study was undertaken to evaluate the therapeutic effect of APL-1 and its combination with methotrexate (MTX) in collagen-induced arthritis (CIA). CIA was induced in male DBA/1 mice at 8 weeks of age by immunization with chicken collagen. APL, MTX or both were administrated beginning from arthritis onset. Therapeutic effect was evaluated by arthritis and joint pathologic scores. In addition, TNFα and IL-10 in sera were measured by ELISA. Treg induction was assessed by FACS analysis. APL-1 inhibits efficiently the course of arthritis in CIA, similar to MTX. In addition, therapy with APL-1 plus MTX reduced CIA in mice, associated with an increase in Treg. These facts reinforce the therapeutic possibilities of APL-1 as a candidate drug for treatment of RA.
28636167 Berberine ameliorates collagen-induced arthritis in rats by suppressing Th17 cell response 2017 Sep Berberine, an isoquinoline alkaloid, has been reported to ameliorate various autoimmune diseases including rheumatoid arthritis by oral administration. However, its mechanism remains mysterious due to an extremely low bioavailability. The fact that berberine readily accumulates in the gut, the largest endocrine organ in the body, attracted us to explore its anti-arthritic mechanism in view of the induction of intestinal immunosuppressive neuropeptides. In this study, berberine (200 mg·kg(-1) , i.g.) was shown to ameliorate collagen-induced arthritis in rats, which was manifested by the reduction of clinical signs and joint destruction, as well as marked down-regulation of Th17 cell frequency and interleukin-17 level in blood. In contrast, an intravenous injection of berberine failed to affect arthritis in rats, implying that its anti-arthritic effect was gut-dependent. Further studies revealed that oral berberine selectively elevated the levels of cortistatin, of five gut-derived neuropeptides tested, in the intestines and sera of arthrititic rats. Antagonists of ghrelin/growth hormone secretagogue receptor 1 (a subtype of cortistatin receptor) almost completely abolished the ameliorative effect of berberine on arthritis and Th17 cell responses in rats. In vitro, berberine showed a moderate ability to promote the expression of cortistatin in nerve cells, which was strengthened when the nerve cells were cocultured with enteroendocrine cells to induce an autocrine/paracrine environment. In summary, oral berberine exerted anti-arthritic effect through inhibiting the Th17 cell response, which was closely associated with the induction of cortistatin generation from gut through augmenting autocrine/paracrine action between enteric nerve cells and endocrine cells.
30065453 Serum Calprotectin in Rheumatoid Arthritis: A Promising Diagnostic Marker, How Far Is It R 2017 Jan BACKGROUND: In the past 2 decades, there has been increasing interest in calprotectin. It is released and detected in serum and body fluids as a potentially useful clinical inflammatory marker. The protein has been described in synovial tissue in rheumatoid arthritis (RA) patients, specifically in the lining layer adjacent to the cartilage-pannus junction, which is the primary site of cartilage destruction and bone erosion. Assessment of inflammatory activity in RA is of pivotal importance for the optimal treatment. Our aim in this study is to measure the serum calprotectin levels in RA patients and to assess its association-if there is any-with disease activity score and radiological findings using the musculoskeletal ultrasound. PATIENTS AND METHODS: In our case control study, we included 44 RA patients (Group I) and 20 age- and sex-matched healthy volunteers who served as the control group (Group II). Both groups were subjected to full history taking and thorough clinical examination. Assessment of RA disease activity state was done for all RA patients using the Disease Activity Score 28. Laboratory investigations included the measurement of complete blood cell count, erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor, anticitrullinated peptide antibodies, kidney, liver functions; serum calprotectin levels were determined using enzyme-linked immunosorbent assay and radiological joint assessment was done using musculoskeletal ultrasound score. RESULTS: There was a statistically significant elevation of serum calprotectin levels among RA patients when compared with healthy controls. Statistically significant correlations were also found between serum calprotectin and the ultrasound grading score, Disease Activity Score 28, and erythrocyte sedimentation rate, which reflect the degree of inflammatory activity in the affected joints in RA patients. Moreover, the study yielded a significant correlation between serum calprotectin levels and rheumatoid autoantibodies (rheumatoid factor and anticitrulli-nated peptide antibodies), which are strong predictors of the aggressiveness of the disease. Serum calprotectin at a cutoff level of 93.9 μg/dL had 88.6% sensitivity and 100% specificity for diagnosis of RA. CONCLUSION: Calprotectin was found to have high association with laboratory and ultrasonography markers of inflammation in RA patients, so it is recommended for use as a marker of inflammatory activity in RA patients especially for the follow-up of patients on biological therapy to assess its efficacy.
29225602 Sphingosine-1-Phosphate Promotes the Persistence of Activated CD4 T Cells in Inflamed Site 2017 Inflammation can be protective or pathogenic depending on context and timeframe. Acute inflammation, including the accumulation of CD4 T cells, accompanies protective immune responses to pathogens, but the presence of activated CD4 T cells at sites of inflammation is associated with chronic inflammatory disease. While significant progress has been made in understanding the migration of CD4 T cells into inflamed sites, the signals that lead to their persistence are poorly characterized. Using a murine ear model of acute inflammation and intravital two-photon imaging, we have dissected the signals that mediate CD4 T cell persistence. We report the unexpected finding that the bioactive lipid, sphingosine-1-phosphate (S1P), is both necessary and sufficient for the persistence of activated CD4 T cells at peripheral tissues in acute inflammation. S1P mediated the enhanced motility of CD4 T cells at inflamed tissues but did not affect their migration to the downstream draining lymph node. We found that sphingosine kinase-1, which regulates S1P production is increased at inflamed sites in mice and in patients with the chronic inflammatory disease, rheumatoid arthritis. Together, these data suggest that S1P, or its regulators, may be key targets to promote or disrupt accumulation of CD4 T cells at inflamed tissues.
28971075 Relationship between Sleep, Pain and Inflammatory Markers in Patients with Rheumatoid Arth 2017 Sep Introduction: Rheumatoid Arthritis (RA) is known as a progressive chronic auto-immune disease. Measurement of inflammatory markers are applied for follow up the activity of disease. So determining factors that effects these markers such as sleep and pain can help to prevent the severity of disease. The aim of study was to determine the relationship between sleep disorders, pain and inflammatory markers in patients with RA. Methods: Participants included 210 patients with RA referred to educational medical clinics of Imam Reza and Sina in Tabriz selected by convenience sampling. They were assessed by Sleep Disorders Questionnaire (SDQ) and Epworth Sleepiness Scale (ESS). Visual Analog Scale (VAS) also applied for pain measurement. Data were analyzed using SPSS ver.13 by descriptive and inferential statistics. Results: Most of participants (74%) were female, the mean age of participants was 48.41 years. The mean (SD) of sleepiness was 13.14 (5.6) and pain 6.09 (2.14). Significant relationship obtained between sleep disorders and pain. As well as sleep problems had significant relation with CRP. Also pain had significant correlation with inflammatory markers. Conclusion: Sleep pattern in RA appears to be disrupted by pain. Pain severity and sleep problems can predict increasing inflammatory markers that can be a clues of intensity of disease. So relieving pain and improved sleep can decrease the intensity of disease.
29096669 Anti-carbamylated protein antibodies precede disease onset in monkeys with collagen-induce 2017 Nov 2 BACKGROUND: Rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPA) and anti-carbamylated protein (anti-CarP) antibodies are rheumatoid arthritis (RA)-associated autoantibodies. Besides their presence in human serum, anti-CarP antibodies have also been described in rodent models of arthritis, while ACPA are not consistently detectable. Data on these RA-associated autoantibodies in primates are not available. Therefore, we investigated the presence of RF, anti-CarP antibodies and ACPA in rhesus monkeys before and after collagen-induced arthritis immunizations. METHODS: In previous studies, arthritis was induced in groups of rhesus monkeys by immunisation with collagen following pre-treatment with placebo, abatacept or Roactemra. Previously collected serum was used to measure, autoantibodies by ELISA, detecting anti-CarP antibodies, RF-IgM and antibodies against CCP2, citrullinated myelin basic protein and citrullinated fibrinogen. RESULTS: Out of the three autoantibodies, only anti-CarP antibodies were detectable in resus monkeys with arthritis. RF-IgM and ACPA were undetectable and below the detection limit of the ELISA. The level of anti-CarP antibodies increases over time and, similar to in humans and mice, these autoantibodies were already detectable before clinical disease onset. Furthermore, preventive treatment with abatacept (CTLA4/IgG1-Fc fusion protein) inhibited the development of anti-CarP antibodies after immunization, while this was less evident for preventive Roactemra (anti-IL6-receptor) treatment. Moreover, disease progression was only reduced following abatacept treatment. CONCLUSION: Rhesus monkeys develop anti-CarP antibodies upon induction of collagen-induced arthritis, while we were unable to detect RF or ACPA. Also, the development of anti-CarP antibodies could be inhibited by preventive abatacept treatment.
28457902 Anti-rheumatoid arthritis effects of traditional Chinese herb couple in adjuvant-induced a 2017 Jun 9 ETHNOPHARMACOLOGICAL RELEVANCE: Clematis chinensis Osbeck / Notopterygium incisum Ting ex H, T-Chang (CN) is a traditional Chinese herb couple with prominent efficacy. The herb couple has been commonly used for clinical treatment of arthralgia syndrome ("Bi Zheng" in Chinese) for centuries in China, including rheumatic arthritis, osteoarthritis and gout in modern medicine. AIM OF THE STUDY: To evaluate the anti-arthritic effect of CN herb couple in a rat model of rheumatoid arthritis (RA). MATERIALS AND METHODS: Rats were divided randomly into six groups with eight each. Adjuvant-induced arthritis (AIA) model was established by intradermal injection of complete Freund's adjuvant (CFA). Rats were treated orally with different dosages of CN (0.7g/kg, 2.1g/kg, 6.3g/kg) from day 16 till day 40. Ibuprofen (50.4mg/kg) served as a positive control. Spontaneous activity, body weight, paw swelling, and arthritis index (AI) were monitored throughout drug treatment. Then serum levels of tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), and vascular endothelial growth factor (VEGF) were determined by enzyme linked immunosorbent assay (ELISA) kits. In addition, histopathological examination and immunohistochemistry were used to assess the severity of arthritis. RESULTS: Three dosage of CN significantly ameliorated symptoms of RA via increasing body weight as well as reducing paw swelling (at dose of 6.3g/kg, p<0.01) in AIA rats. An extremely significant reduction of AI (p<0.001) was also observed with treatment of CN (6.3g/kg) compared with model group. In parallel, treatment of CN significantly down-regulated levels of TNF-α, IL-6, and VEGF both in serum (p<0.01) and in joint synovial compared with model rats. And histopathology revealed noticeable reduction in synovial hyperplasia, cartilage damage, and inflammatory infiltration by CN treatment, especially at dose of 6.3g/kg. CONCLUSIONS: To conclude, all results suggest that CN possesses evident anti-arthritic effects in AIA rats.