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ID PMID Title PublicationDate abstract
27091275 Health-related quality of life and its predictors among patients with rheumatoid arthritis 2016 May BACKGROUND: Limited studies have examined the predictors of HRQoL among patients with rheumatoid arthritis. This study helped to ascertain the predictors of HRQoL from the pool of influencing factors identified by previous studies. AIM: This study investigated the health-related quality of life (HRQoL) of adult patients with rheumatoid arthritis and its predictors. METHODS: Using a descriptive correlational design, this study explored the relationship between HRQoL and pain, functional disability, anxiety, depression, medication adherence and social support. Eligible outpatients (n=108) were recruited via their attending doctors who were co-investigators of this study. Informed consent forms were distributed and questionnaires administered in a teaching hub by the main researcher. RESULTS: Significant correlations were found between HRQoL and all of the study variables. Pain, functional disability and depression were main predictors of HRQoL. CONCLUSIONS: Future evidence-based interventions focusing on pain relief, delaying disability or improving functional ability and reducing depressive symptoms are required to enhance the HRQoL of patients with rheumatoid arthritis.
26683195 In rheumatoid arthritis, country of residence has an important influence on fatigue: resul 2016 Apr OBJECTIVES: To investigate the relationship between country of residence and fatigue in RA, and to explore which country characteristics are related to fatigue. METHODS: Data from the multinational COMORA study were analysed. Contribution of country of residence to level of fatigue [0-10 on visual analogue scale (VAS)] and presence of severe fatigue (VAS ⩾ 5) was explored in multivariable linear or logistic regression models including first socio-demographics and objective disease outcomes (M1), and then also subjective outcomes (M2). Next, country of residence was replaced by country characteristics: gross domestic product (GDP), human development index (HDI), latitude (as indicator of climate), language and income inequality index (gini-index). Model fit (R(2)) for linear models was compared. RESULTS: A total of 3920 patients from 17 countries were included, mean age 56 years (s.d. 13), 82% females. Mean fatigue across countries ranged from 1.86 (s.d. 2.46) to 4.99 (s.d. 2.64) and proportion of severe fatigue from 14% (Venezuela) to 65% (Egypt). Objective disease outcomes did not explain much of the variation in fatigue ([Formula: see text] = 0.12), while subjective outcomes had a strong negative impact and partly explained the variation in fatigue ([Formula: see text]= 0.27). Country of residence had a significant additional effect (increasing model fit to [Formula: see text] = 0.20 and [Formula: see text] = 0.36, respectively). Remarkably, higher GDP and better HDI were associated with higher fatigue, and explained a large part of the country effect. Logistic regression confirmed the limited contribution of objective outcomes and the relevant contribution of country of residence. CONCLUSION: Country of residence has an important influence on fatigue. Paradoxically, patients from wealthier countries had higher fatigue.
24219063 The association between serum vitamin D Level and disease activity in Thai rheumatoid arth 2016 Apr BACKGROUND: Serum vitamin D level was inversely associated with the risk of developing new onset rheumatoid arthritis (RA) and disease activity, but some conflicting results have been reported. OBJECTIVE: To examine the serum vitamin D status in Thai RA patients and possible independent factors affecting serum 25 hydroxyvitamin vitamin D (25(OH)D) and the associations of serum 25(OH)D level and the disease activity and functional status in Thai RA patients. METHODS: A cross-sectional study was performed in 239 Thai RA patients. The blood levels of 25(OH)D2 and D3 were measured by chemiluminescent immunoassay. Disease activity was assessed according to tender and swollen joint counts, erythrocyte sedimentation rate (ESR), visual analog scale for global patient assessment, Disease Activity Score-28 (DAS-28) and Thai Health Assessment Questionnaire (Thai HAQ). RESULT: The mean vitamin D level was 28.79 ng/mL. There were no associations between 25(OH)D levels and number of tender and swollen joint counts, DAS-28 score, HAQ score or rheumatoid factor (RF) and/or anti-cyclic citrulinated peptide (CCP) positivity. After multivariated analysis, Bangkok residents, non-farmer, obesity and non-vitamin D supplementation were the predictors for vitamin D insufficiency in Thai patients with RA. CONCLUSION: There are no associations of serum 25(OH)D levels with disease activity or functional status in Thai RA patients. The factors associated with vitamin D insufficiency are Bangkok resident, non-farmer, obesity and not taking vitamin D supplementation.
27295367 An update on dietary phenolic compounds in the prevention and management of rheumatoid art 2016 Jul 13 Certain nutritional components influence the cellular metabolism and interfere in the pathological inflammatory process, so that they may act as a coadjuvant in the treatment of many chronic inflammatory diseases, including rheumatoid arthritis (RA). Particularly, a wide range of evidence has demonstrated the beneficial roles of dietary phenolic compounds in RA because of their ability to modulate pro-oxidant and pro-inflammatory pathways reducing the onset of arthritic disease progression. These natural phenolic compounds can modulate both the action and the production of inflammatory mediators either directly or indirectly by modulating the action of other molecules involved in RA pathology. Subsequently, the purpose of this article is to review the main in vitro and in vivo studies in RA, which have documented interesting insights into the antioxidant, anti-inflammatory, and immunomodulatory properties of dietary phenolic compounds focusing on their molecular action mechanisms involved in RA. The observations reported above are promising and suggest that the dietary phenolic compounds may influence the course of RA, ameliorating the RA symptoms and downregulating the inflammation at the molecular level; however, most of the studies conducted to date have been preclinical. Thus, future studies should therefore focus more on understanding the efficacy of these phenolic compounds in humans and bringing them to the forefront of the treatment of chronic human diseases.
26408898 Short Communication: Lack of association between MTHFR gene polymorphisms and response to 2015 Sep Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms have been reported to be associated with response to methotrexate (MTX) in certain populations of patients with rheumatoid arthritis (RA). This study aims at investigating any relationship of two single nucleotide polymorphisms (SNPs) in MTHFR gene, C677T and A1298C with response to therapy with MTX in Pakistani RA patients. Allelic frequencies of the two polymorphisms (C677T and A1298C) were determined in 67 RA patients (9 males and 58 females; mean age 42.87 ± 13.5 years) who had previously participated in a prospective clinical trial. Fifty-one patients had received MTX and were followed up for response up to 6 months. Genotyping of the two MTHFR polymorphisms was carried out using PCR-RFLP, while fasting concentration of plasma homocysteine was determined using a kit method. Twenty-eight patients were found to be "good responders", while twenty-three were "poor responders". MTHFR 1298C and MTHFR 677T alleles' frequencies in "good responders" were not different from frequencies in "poor responders" (0.574 vs. 0.521; p=0.6 and 0.197 vs. 0.196; p=0.75, respectively). Plasma homocysteine levels in female RA patients were significantly higher compared to general population in Karachi (13.1 ± 6.7 µmol/l vs. 11.4 ± 5.3 µmol/l; p<0.001). MTHFR C677T and A1298C polymorphisms are not associated with response to MTX in a population of Pakistani RA patients.
26200188 Serious infection during etanercept, infliximab and adalimumab therapy for rheumatoid arth 2016 Jun The purpose of this review is to establish whether there is a significantly increased incidence of serious infections during treatment for rheumatoid arthritis (RA) with etanercept, infliximab or adalimumab, to determine the background risk of serious infection in RA patients without treatment with any biological therapy and to ascertain which organisms are involved in serious infections in RA patients while being treated with etanercept, infliximab or adalimumab. Randomised controlled trials (RCTs), meta-analyses of RCTs, Cochrane reviews, national registry articles and case reports were identified using PubMed/MEDLINE, The Cochrane Library and Google Scholar. The medical subject heading "rheumatoid arthritis" was combined with "serious infection" or "infection" or "adverse drug events" with each of the three reference biological therapies separately: etanercept, infliximab and adalimumab. These electronic searches were limited to human studies, adult studies, those published in the last 10 years (2004-14) and in the English language. Studies which involved the tumor necrosis factor-α inhibitors certolizumab pegol or golimumab were excluded. The background risk of serious infection appears to be approximately two-fold more than non-RA patients before any treatment with biological therapy. The national registries, which may represent the typical RA patient more accurately than clinical trials, suggest a small but significantly increased incidence of serious infection ranging 1.2-2.78 times that of control (treatment with methotrexate). Mycobacteria spp., Staphyloccus aureus, Listeria monocytogenes, Varicella zoster virus and Leishmania species (spp.) repeatedly appear in the case report literature and should be in the mind of the clinician faced with a serious infection in a RA patient with an unknown pathogen who is being treated with either etanercept, infliximab or adalimumab.
25498119 Familial aggregation of arthritis-related diseases in seropositive and seronegative rheuma 2016 Jan OBJECTIVES: Our objective was to estimate the risk of developing rheumatoid arthritis (RA) associated with a family history of non-RA arthritis-related diseases. This familial co-aggregation is of clinical interest since it is often encountered when assessing family history of RA specifically, but also informative on the genetic overlap between these diseases. Since anticitrullinated peptide antibodies/rheumatoid factor (RF)-positive and RF-negative RA have both specific and shared genetic factors, the familial co-aggregation was assessed separately for seropositive and seronegative disease. METHODS: Nested case-control study in prospectively recorded Swedish total population data. The Multi-Generation Register identified first-degree relatives. RA and arthritis-related diseases were ascertained through the nationwide patient register. RA serology was based on International Classification of Diseases tenth revision coded diagnoses, mainly reflecting RF. Familial risks were calculated using conditional logistic regression. Results were replicated using the Swedish rheumatology register. RESULTS: Familial co-aggregation was found between RA and every studied arthritis-related disease, but the magnitude varied widely, from juvenile idiopathic arthritis (JIA) (seropositive RA OR=3.98 (3.01 to 5.26); seronegative RA OR=5.70 (3.47 to 9.36)) to osteoarthritis (seropositive RA OR=1.03 (1.00 to 1.06); seronegative RA OR=1.05 (1.00 to 1.09)). The familial co-aggregation pattern of non-RA arthritis-related diseases was overall similar for seropositive and seronegative RA. Among those with family history of RA, relatives' other arthritis-related diseases conferred little or no additional risk. CONCLUSIONS: Although family history of several arthritis-related diseases may be useful to predict RA (eg, lupus and JIA), others (eg, osteoarthritis and arthralgia) are less useful. Seropositive and seronegative RA had rather similar familial co-aggregation patterns with arthritis-related diseases, suggesting that the two RA subsets are similar in the genetic factors that overlap with these diseases.
26171869 Reliability of Box and Block Test for manual dexterity in patients with rheumatoid arthrit 2016 Dec OBJECTIVE: This study is aimed to determine the reliability of the Box and Block (B&B) Test for manual dexterity of upper extremity function in patients with rheumatoid arthritis (RA) and to compare the results with age- and sex-matched healthy controls, and also with available normative data. METHODS: The reliability of B&B Test was assessed within and between testers using the intraclass correlation coefficient (ICC) in patients with RA attending rheumatology clinics of Christian Medical College Hospital, India. The dexterity scores of patients were then compared with age- and sex-matched controls and the Mathiowetz's population-based normative data by Student's independent t-test. RESULTS: The interrater and intrarater reliability of the B&B Test in patients with RA (n = 60) ranged from 0.92 to 0.97 and 0.91 to 0.95, respectively. The dexterity scores in patients with RA were lower as compared to the control group (dominant hand 54.87 vs. 68.18, P < 0.001; contralateral hand 52.65 vs. 65.6, P < 0.001) and population-based normative score (dominant hand 54.87 vs. 80.02, P < 0.001; contralateral hand 52.65 vs. 77.23; P < 0.001). The control group scores were also lower than the normative data. Higher age of patient, longer disease duration and higher disease activity reflected by Disease Activity Score of 28 joints (DAS-28) also correlated well with lower dexterity score. CONCLUSIONS: The B&B Test is a reliable tool for assessing upper extremity function in patients with RA and the dexterity scores are lower for RA patients. The scores had correlation with age, disease duration and disease activity.
24983407 Inhibition of radiographic joint damage in rheumatoid arthritis patients in DAS28 remissio 2015 Jan OBJECTIVE: We retrospectively investigated the inhibitory effect on radiographic joint damage (RJD) for non-biological disease-modifying antirheumatic drug (non-bioDMARD) monotherapy or methotrexate (MTX) combination therapy for rheumatoid arthritis (RA) in the disease activity score with 28 joint counts with erythrocyte sedimentation rate (DAS28) remission. METHODS: Eighty-four patients (55 cases of monotherapy, 29 cases of MTX-combination therapy) in DAS28 remission (DAS28 ≤ 2.6) were investigated from 538 RA patients newly registered between February 2007 and August 2010. The patients were analyzed for radiological assessments using the modified total Sharp score/year (mTSS/y). RESULTS: The remission rates and ΔmTSS/y for each agent using monotherapy were 7.1% and 0.17 for sulfasalazine; 11.9% and 0.49 for bucillamine (BUC); and 23.9% and 2.06 for MTX. Those using combination therapy were 6.8% and 1.39 for MTX + BUC; 23.5% and -1.64 for MTX + leflunomide; and 8.0% and 0.31 for MTX + tacrolimus. The cumulative distribution in the single and combination therapy groups showed improvement of percentages in structural remission from baseline to 1-year treatment, 34.1% to 60.9% (P < 0.05) and from 0% to 56.7%(P < 0.0001), respectively. Baseline mTSS (r = 0.67, P < 0.0001), disease duration (r = 0.40, P < 0.01), swollen joint counts (r = 0.33, P < 0.05), and anti-cyclic citrullinated peptide antibody (r = 0.31, P < 0.05) were useful predictors of RJD for non-bioDMARD monotherapy, but not for combination therapy. CONCLUSION: Satisfactory inhibition of RJD was observed in the DAS28 remission cases of monotherapy or MTX combination therapy with a non-bioDMARD.
26349791 Protective role of theophylline and their interaction with nitric oxide (NO) in adjuvant-i 2015 Dec Theophylline (non-specific PDE inhibitor) and their interactions with nitric oxide modulators were evaluated in adjuvant-induced arthritic model of rats. Wistar rats (200-300g), 8 animals per group were used in the study. The animals were injected with 0.1mL of squalene and 0.2mL of complete Freund's adjuvant on day (0) in sub-planter region of right hind paw controls received only saline. The treatment with theophylline and nitric oxide modulators were done from day 14 to day 28. Arthritis indexes, ankle diameter, paw volume, and body weight were determined to assess RA progression from day (0) to day 28. On day 28 animals were sacrificed and their blood collected for IL-10 and TNF-α cytokine levels and hind paw for pathological analysis. Synovial fluid from joint spaces of CFA inoculated rats was collected to estimate TNF-α level in synovial fluid. The data obtained was analyzed by two-way ANOVA followed by the Newman-Keuls post-hoc test. Theophylline (10 and 20mg/kg) significantly decreased adjuvant induced increased arthritis-index, paw volume and ankle diameter (p<0.05 in all parameters) compared to only adjuvant control group. It also reversed adjuvant induced slight decrease in body weight to normalcy. l-Arginine 100mg/kg+theophylline 20mg/kg suppressed TNF-α and elevates IL-10 level as well as reversed adjuvant-induced elevated arthritic parameters as compared to only adjuvant and prednisone group (p<0.001). Synovial TNF-α level of adjuvant only group was several fold higher than its serum level. Treatment with theophylline 20mg/kg significantly reduces synovial TNF-α level as compared to adjuvant only group. Theophylline 20mg/kg+L-NAME 10mg/kg significantly reversed these adjuvant-induced changes in immunological, histopathological and arthritis parameters (p<0.05).
27135916 Clinical and metabolic response to probiotic supplementation in patients with rheumatoid a 2016 Sep OBJECTIVE: This study was performed to determine the effects of probiotic supplementation on clinical and metabolic status of patients with rheumatoid arthritis (RA). METHODS: Sixty patients with RA aged 25-70 years were assigned into two groups to receive either probiotic capsules (n = 30) or placebo (n = 30) in this randomized, double-blind, placebo-controlled trial. The patients in the probiotic group received a daily capsule that contained three viable and freeze-dried strains: Lactobacillus acidophilus (2 × 10(9) colony-forming units [CFU]/g), Lactobacillus casei (2 × 10(9) CFU/g) and Bifidobacterium bifidum (2 × 10(9) CFU/g) for 8 weeks. The placebo group took capsules filled with cellulose for the same time period. Fasting blood samples were taken at the beginning and the end of the study to quantify related markers. RESULTS: After 8 weeks of intervention, compared with the placebo, probiotic supplementation resulted in improved Disease Activity Score of 28 joints (DAS-28) (-0.3 ± 0.4 vs. -0.1 ± 0.4, P = 0.01). In addition, a significant decrease in serum insulin levels (-2.0 ± 4.3 vs. +0.5 ± 4.9 μIU/mL, P = 0.03), homeostatic model assessment-B cell function (HOMA-B) (-7.5 ± 18.0 vs. +4.3 ± 25.0, P = 0.03) and serum high-sensitivity C-reactive protein (hs-CRP) concentrations (-6.66 ± 2.56 vs. +3.07 ± 5.53 mg/L, P < 0.001) following the supplementation of probiotics compared with the placebo. Subjects who received probiotic capsules experienced borderline statistically significant improvement in total- (P = 0.09) and low-density lipoprotein-cholesterol levels (P = 0.07) compared with the placebo. CONCLUSION: Overall, the results of this study indicated that taking probiotic supplements for 8 weeks among patients with RA had beneficial effects on DAS-28, insulin levels, HOMA-B and hs-CRP levels.
27964760 Impact of body weight on the achievement of minimal disease activity in patients with rheu 2016 Dec 13 BACKGROUND: In this study, we evaluated the impact of obesity and/or overweight on the achievement of minimal disease activity (MDA) in patients with psoriatic arthritis (PsA) and patients with rheumatoid arthritis (RA) receiving an anti-rheumatic treatment. Obesity can be considered a low-grade, chronic systemic inflammatory disease and some studies suggested that obese patients with rheumatic diseases exhibit a lower rate of low disease activity achievement during treatment with anti-rheumatic drugs. METHODS: A systematic search was performed in major electronic databases (PubMed, Web of Science, Scopus, Embase) to identify studies reporting MDA achievement in obese and/or overweight patients with RA or PsA and in normal-weight RA or PsA control subjects. Results were expressed as Odds Ratios (ORs) with pertinent 95% Confidence Intervals (95%CIs). RESULTS: We included 17 studies (10 on RA and 7 on PsA) comprising a total of 6693 patients (1562 with PsA and 5131 with RA) in the analysis. The MDA achievement rate was significantly lower in obese patients than in normal-weight subjects (OR 0.447, 95% CI 0.346-0.577, p < 0.001, I (2) = 62.6%, p < 0.001). Similarly, overweight patients showed a significantly lower prevalence of MDA achievement than normal-weight subjects (OR 0.867, 95% CI 0.757-0.994, p = 0.041, I (2) = 64%, p = 0.007). Interestingly, the effect of obesity on MDA was confirmed when we separately analyzed data on patients with RA and patients with PsA. In contrast, when we evaluated the effect of overweight, our results were confirmed for PsA but not for RA. A meta-regression analysis showed that follow-up duration, age, male sex, and treatment duration are covariates significantly affecting the effect of obesity/overweight on MDA achievement. CONCLUSIONS: The results of our meta-analysis suggest that obesity and overweight reduce the chances to achieve MDA in patients with rheumatic diseases receiving treatment with traditional or biologic disease-modifying antirheumatic drugs.
27082252 Comparison of molecular mechanisms of rheumatoid arthritis and osteoarthritis using gene m 2016 Jun The present study aimed to compare the molecular mechanisms of rheumatoid arthritis (RA) and osteoarthritis (OA). The microarray dataset no. GSE29746 was downloaded from Gene Expression Omnibus. After data pre‑processing, differential expression analysis between the RA group and the control, as well as between the OA group and the control was performed using the LIMMA package in R and differentially expressed transcripts (DETs) with |log2fold change (FC)|>1 and P<0.01 were identified. DETs screened from each disease group were then subjected to functional annotation using DAVID. Next, DETs from each group were used to construct individual interaction networks using the BIND database, followed by sub‑network mining using clusterONE. Significant functions of nodes in each sub‑network were also investigated. In total, 19 and 281 DETs were screened from the RA and OA groups, respectively, with only six common DETs. DETs from the RA and OA groups were enriched in 8 and 130 gene ontology (GO) terms, respectively, with four common GO terms, of which to were associated with phospholipase C (PLC) activity. In addition, DETs screened from the OA group were enriched in immune response‑associated GO terms, and those screened from the RA group were largely associated with biological processes linked with the cell cycle and chromosomes. Genes involved in PLC activity and its regulation were indicated to be altered in RA as well as in OA. Alterations in the expression of cell cycle‑associated genes were indicated to be linked with the occurrence of OA, while genes participating in the immune response were involved in the occurrence of RA.
27094600 Autoantibodies to two novel peptides in seronegative and early rheumatoid arthritis. 2016 Aug OBJECTIVES: Despite recent progress in biomarker discovery for RA diagnostics, still over one-third of RA patients-and even more in early disease-present without RF or ACPA. The aim of this study was to confirm the presence of previously identified autoantibodies to novel Hasselt University (UH) peptides in early and seronegative RA. METHODS: Screening for antibodies against novel UH peptides UH-RA.1, UH-RA.9, UH-RA.14 and UH-RA.21, was performed in two large independent cohorts. Peptide ELISAs were developed to screen for the presence of antibodies to UH-RA peptides. First, 292 RA patients (including 39 early patients), 90 rheumatic and 97 healthy controls from UH were studied. Antibody reactivity to two peptides (UH-RA.1 and UH-RA.21) was also evaluated in 600 RA patients, 309 patients with undifferentiated arthritis and 157 rheumatic controls from the Leiden Early Arthritis Clinic cohort. RESULTS: In both cohorts, 38% of RA patients were seronegative for RF and ACPA. Testing for autoantibodies to UH-RA.1 and UH-RA.21 reduced the serological gap from 38% to 29% in the UH cohort (P = 0.03) and from 38% to 32% in the Leiden Early Arthritis Clinic cohort (P = 0.01). Furthermore, 19-33% of early RA patients carried antibodies to these peptides. Specificities in rheumatic controls ranged from 82 to 96%. Whereas antibodies against UH-RA.1 were related to remission, anti-UH-RA.21 antibodies were associated with inflammation, joint erosion and higher tender and swollen joint counts. CONCLUSION: This study validates the presence of antibody reactivity to novel UH-RA peptides in seronegative and early RA. This might reinforce current diagnostics and improve early diagnosis and intervention in RA.
27599556 Heparin inhibits the inflammation and proliferation of human rheumatoid arthritis fibrobla 2016 Oct Fibroblast-like synoviocytes (FLSs) of rheumatoid arthritis (RA) lead to cartilage destruction, and the activation of NF‑κB is important in the proliferation of FLSs. Heparin is a glycosaminoglycan, which is widely used as an anticoagulant. In the present study, the effect of heparin on the tumor necrosis factor (TNF)‑α induced proliferation of FLSs was investigated. Western blot and polymerase chain reaction analyses were used to assess the expression levels of cytokines. The results revealed that TNF‑α induced the expression of interleukin (IL)‑6, IL‑8, TNF‑α and cyclin D1. Heparin inhibited the growth rate of the FLSs induced by TNF‑α. Heparin also decreased the TNF‑α‑induced mRNA and protein expression levels of IL‑6, IL‑8, TNF‑α and cyclin D1 in a dose‑dependent manner. Immunofluorescence analysis showed that the expression of cytoplasmic TNF‑α was significantly reduced by heparin treatment. Furthermore, the levels of p65 and inhibitor of nuclear factor (NF)‑κB phosphorylation were inhibited by heparin treatment, suggesting that heparin induced the inhibition of NF‑κB. In conclusion, the results of the present study revealed that heparin inhibited the TNF‑α‑induced proliferation, cytokine production, expression of cyclin D1 and activation of NF‑κB signaling in FLSs, indicating the therapeutic potential of heparin in the treatment of RA.
26802181 Ultrasound findings predict progression to inflammatory arthritis in anti-CCP antibody-pos 2016 Dec OBJECTIVES: To determine whether ultrasound can identify anti-cyclic citrullinated peptide (anti-CCP) antibody-positive patients without clinical synovitis (CS) who progress to inflammatory arthritis (IA). METHODS: In a prospective study, anti-CCP-positive patients without CS underwent ultrasound imaging of 32 joints (wrists, metacarpophalangeal joints, proximal interphalangeal joints and metatarsophalangeal joints (MTPs)) and were monitored for the development of IA. Associations between baseline ultrasound findings (grey scale (GS), power Doppler (PD) and erosions) and (1) progression to IA and (2) development of CS within an individual joint were measured. RESULTS: Consecutive anti-CCP-positive patients (n=136; mean age 51 years, 100 women) were followed up for median of 18.3 months (range 0.1-79.6). At baseline 96% had GS, 30% had PD and 21% had one or more erosions. IA developed in 57 patients (42%) after median of 8.6 months (range 0.1-52.4). Ultrasound abnormalities (GS ≥2, PD ≥1 or erosion ≥1) were found in 86% at baseline compared with 67% of non-progressors (χ(2)=6.3, p=0.012). Progression to IA was significantly higher in those with ultrasound findings in any joint (excluding MTPs for GS) (GS ≥2: 55% vs 24%, HR (95% CI) 2.3 (1.0 to 4.9), p=0.038; PD ≥2: 75% vs 32%, 3.7 (2.0 to 6.9), p<0.001 and erosion ≥1: 71% vs 34%, 2.9 (1.7 to 5.1), p<0.001). Furthermore, progression occurred earlier with PD ≥2 (median 7.1 vs 52.4 months) and erosion ≥1 (15.4 vs 46.5). At the individual joint level, the trend for progression to CS was more significant for GS and PD (GS ≥2: 26% vs 3%, 9.4 (5.1 to 17.5), p<0.001; PD ≥2: 55% vs 4%, 31.3 (15.6 to 62.9), p<0.001). CONCLUSION: Ultrasound features of joint inflammation may be detected in anti-CCP-positive patients without CS. Ultrasound findings predict progression (and rate of progression) to IA, with the risk of progression highest in those with PD signal. TRIAL REGISTRATION NUMBER: NCT02012764; Results.
27984139 Fc fragments of immunoglobulin G are an inductor of regulatory rheumatoid factor and a pro 2017 Feb We recently identified rheumatoid factor, the production of which neither predicts nor exacerbates experimental autoimmune disease, but the opposite, namely it is associated with autoimmune disease resistance and remission. We have named it regulatory rheumatoid factor (regRF). The aim of this study was to determine whether rat Fc fragments and human Fc fragments are an antigen for regRF, and to determine the conditions for obtaining them. The presence of an antigenic determinant for regRF on IgG fragments was inferred from the fragments' ability to inhibit the agglutination caused by regRF and to induce regRF production in vivo. It was found that antigenic determinants for both human regRF and rat regRF are absent from native IgG and can be induced in the hinge region of Fc fragments of homologous IgG by papain digestion. The rat Fc fragments are susceptible to spontaneous reconfiguration, which results in loss of the antigenic determinants for regRF. Reconfiguration can be observed by SDS-PAGE. Immunization of arthritic rats with Fc fragments of rat IgG that carry antigenic determinants for rat regRF reduces the symptoms of collagen-induced arthritis. The Fc fragments can be viewed as the basis for a therapeutic vaccine to suppress autoimmune responses.
27026419 Ultrasound power Doppler synovitis is associated with plasma IL-6 in established rheumatoi 2016 Jul BACKGROUND AND OBJECTIVE: Cytokines have an important role in the pathogenesis of rheumatoid arthritis (RA). Although plasma levels of IL-6 have been related to musculoskeletal ultrasound (MSUS) synovitis in early DMARD-naïve RA, there are no similar studies in established disease. METHODS: 64 RA patients treated with non-biological DMARDs and 30 healthy controls were included in this prospective cross-sectional study. A blood sample was taken before evaluation of disease activity (DAS28) and ultrasonography (all tests performed in a blinded fashion). MSUS was performed by one of two ultrasound-trained rheumatologists on 10 joints of both hands. Gray scale (GS) and pD (power Doppler) synovitis were evaluated using a semi-quantitative scale (0-3) in individual joints, and their sum (score 10) was calculated. Plasma cytokines (IL-2, IL-4, IL-6, IL-10, IL-17, TNF, IFN-γ, and VEGF) were quantified by flow cytometry. RESULTS: Levels of all cytokines, excepting VEGF, were significantly higher in RA patients than in controls (P⩽0.05). In RA patients, IL-6, but not other cytokines, correlated positively with DAS28 and swollen joint count (P⩽0.01), as well as with 10-joint pD score, and GS and pD of both wrists (P<0.01 for all tests). In multiple linear regression, the association of IL-6 with 10-joint pD score was maintained even after adjustment for DAS28. However, there was no correlation of IL-6 with tender joint count, 10-joint GS score, or presence of erosions. CONCLUSION: We demonstrated an association of inflammatory findings on MSUS and plasma IL-6 independently of DAS28 in established RA.
26238094 Factors associated with the intensification of treatment in rheumatoid arthritis in clinic 2015 Nov The aim of the present study was to analyse the patterns of treatment adjustment in rheumatoid arthritis (RA) patients with active disease in routine clinical care. This was a cross-sectional study of consecutive patients with RA conducted in five hospitals. Activity scales (DAS28-ESR) and function (HAQ) were measured, as well as whether ultrasound was performed as part of the assessment. Treatment decision (no changes/reduction/intensification) and time to the next scheduled visit were the outcomes variables. Associated factors were analysed by multilevel regression models. A total of 343 patients were included (77 % women, mean age 57 years, mean RA duration 10 years), of whom 44 % were in remission by DAS28. Treatment was continued in 202 (59 %) patients, reduced in 57 (16 %), and intensified in 83 (24 %). In the 117 patients with active RA (DAS28 ≥ 3.2), treatment was intensified in 61 (52 %). Factors associated with treatment intensification were physician and patient VAS, and DAS28, but not the centre. In the multilevel regression analysis with intensification of treatment as dependent variable, the following factors were significantly associated: DAS28 [OR 3.67 (95 % CI 2.43-5.52)], patient VAS [OR 1.04 (95 % CI 1.01-1.08)], and have performed an ultrasound [OR 3.36 (95 % CI 1.47-7.68)]. Factors associated with time to the next scheduled visit (an average of 4.3 months) were patient and physician VAS, DAS28, and centre. In clinical practice, half of the patients with active RA maintain or reduce the treatment. The decision to intensify treatment in active RA as recommended by a treat-to-target strategy is complex in practice.
25636236 Randomized clinical trials as reflexive-interpretative process in patients with rheumatoid 2015 Aug Patients in randomized clinical trials have to adapt themselves to a restricted language to capture the necessary information to determine the safety and efficacy of a new treatment. The aim of this study was to explore the experience of patients with rheumatoid arthritis after completing their participation in a biologic therapy randomized clinical trial for a period of 3 years. A qualitative approach was used. The information was collected using 15 semi-structured interviews of patients with rheumatoid arthritis. Data collection was guided by the emergent analysis until no more relevant variations in the categories were found. The data were analysed using the grounded theory method. The objective of the patients when entering the study was to improve their quality of life by initiating the treatment. However, the experience changed the significance of the illness as they acquired skills and practical knowledge related to the management of their disease. The category "Interactional Empowerment" emerged as core category, as it represented the participative experience in a clinical trial. The process integrates the follow categories: "weight of systematisation", "working together", and the significance of the experience: "the duties". Simultaneously these categories evolved. The clinical trial monitoring activities enabled patients to engage in a reflexive-interpretative mechanism that transformed the emotional and symbolic significance of their disease and improved the empowerment of the patient. A better communicative strategy with the health professionals, the relatives of the patients, and the community was also achieved.