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ID PMID Title PublicationDate abstract
23285480 Association between the response to B cell depletion therapy and the allele*2 of the HS1,2 2012 Dec 20 OBJECTIVE: Several studies underline the relevance of the genetic background for the response to therapy. We evaluated the relationship between the polymorphism of the HS1,2A enhancer, located in the 3' regulatory region of the heavy immunoglobulin chain (IgH), and the response to B cell depletion therapy (BCDT) with Rituximab (RTX). METHODS: Fifty rheumatoid arthritis (RA) patients (42 women; disease duration 13.9 ± 10.6 years) treated with RTX, not responsive to previous DMARDs and/or TNFα inhibitors therapies, and 220 healthy subjects were enrolled in the study. Patients were genotyped for HS1,2A enhancer polymorphism, as previously described. Disease activity was assessed every three months according to the European League Against Rheumatism's (EULAR) criteria. RESULTS: All RA patients were seropositive for at least one of the tested autoantibodies: rheumatoid factor (FR IgA, FR IgM e FR IgG), anti-cyclic citrullinated peptides (anti-CCP IgA, anti-CCP IgM e anti-CCP IgG) and anti-vimentin antibodies. RA patients had an increased frequency of the allele*2 (60.0%) of the HS1,2A enhancer compared to healthy subjects (42.0%; OR(95%ICs): 2.07 (1.33-3.22)). Patients with a good EULAR response at 6 months follow-up visit had an increased frequency of genotype 2/2 (47.1%) compared to poor-responders RA patients (genotype 2/2: 18.2%, OR(95%ICs): 4.00 (1.09-14.68)). All the patients with a good EULAR response had the allele*2, thus showing a possible association with the allele in this population. CONCLUSIONS: The presence of allele*2 seems to be related to a good response to BCDT with RTX in seropositive RA patients, thus highlighting the role of the HS1,2A enhancer in B cell maturation and class-switch recombination.
22215041 Fibronectin molecular status determination useful to differentiate between rheumatoid arth 2013 Jan To find whether the plasma fibronectin (FN) molecular status can be useful to differentiate between rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). The expression of plasma FN domains was determined by ELISA using monoclonal domain-specific antibodies. FN molecular forms were revealed by immunoblotting and analyzed by densitometry. The following findings were found: (1) Mean values of (Fibrin-Heparin)FN concentration were lower in SLE and RA patients than in normal plasmas. The cut off points at 31 mg/l in SLE and at 45 mg/l in RA showed a sensitivity and specificity of 54, 55 and 75%, respectively. (2) Mean values of concentrations of (CBD)FN and (Ct)FN were lower in SLE than those in normal and RA plasmas. Quantified data showed the cut off points of (CBD)FN and (Ct)FN at 200 mg/l (58% of sensitivity, 56% of specificity) and 350 mg/l (58% of sensitivity, 58% of specificity) in SLE, as well as at 295 mg/l (52% of sensitivity, 51% of specificity) and 460 mg/l in RA (70% of sensitivity, 73% of specificity). (3) The plasma FN immunopatterns, characterized by the presence of high-molecular (260-310 kDa) and/or low-molecular (158-209 kDa) FN bands, were specific only for SLE samples. The analysis of plasma FN status revealed by its Fibrin-Heparin-, CBD- and Ct-domain reactivity with monoclonal antibody and immunoblotting can be helpful to differentiate the SLE in respect to RA and normal plasmas.
22048227 A dose-response meta-analysis for quantifying relative efficacy of biologics in rheumatoid 2011 Dec We present a dose-response meta-analysis to quantify relative efficacy of biologic disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA). There is a strong rationale for this analysis because, although multiple biologics are available, information on head-to-head comparisons is limited. Data on the percentage of patients attaining American College of Rheumatology (ACR) 20, 50, and 70 responses were extracted from 50 randomized controlled trials representing 21,500 patients, five mechanisms of action, and nine biologics. The analysis showed that all tumor necrosis factor inhibitors (anti-TNFs) share the same dose-response relationship for ACR 20, 50, and 70, differing only in potency. Yet there are significant differences in efficacy among the anti-TNFs due to differences in the clinical dose ranges available. At the suggested starting dose, golimumab was the least efficacious, followed by infliximab, adalimumab, etanercept, and certolizumab. Significant differences in the dose-response relationship were found between anti-TNFs and other biologics, resulting in differences in efficacy and differential impact of dose titration.
21418781 Do biologics-naïve patients with rheumatoid arthritis respond better to tocilizumab than 2011 Mar OBJECTIVES: To determine responses to tocilizumab between patients with rheumatoid arthritis (RA) who switched to anti-TNF agents and those who are biologics-naïve. METHODS: This retrospective study investigated 107 patients with RA who were treated with tocilizumab. At baseline, 61 of them had already been treated with anti-TNF agents (switched group; 46 for inefficacy and 15 for adverse events), and 46 were biologics-naïve (naïve group). Treatment responses to tocilizumab at week 12 and 24 were compared between the switched and naïve groups using the disease activity score 28 (DAS28). RESULTS: Forty-two (91.3%) and 50 (82.0%) patients in the naïve and switched groups, respectively, completed 24 weeks of tocilizumab treatment. The DAS28-ESR and DAS28-CRP values (means±SD) at weeks 12 and 24 compared to baseline decreased significantly for the naïve and switched groups. The DAS28-ESR and DAS28-CRP values at weeks 12 and 24 were significantly decreased in the naïve group, compared to the switched group. Disease activity was improved in the naïve patients compared to the switched patients. CONCLUSIONS: Tocilizumab was safe, tolerable, and clinically effective for patients with inadequate responses to anti-TNF therapy and for those who were biologics-naïve, and it was more effective among the latter.
21251863 Role for interferon-gamma release assays in latent tuberculosis screening before TNF-α an 2011 Jul TNF-α antagonist therapy is associated with a risk of severe, extrapulmonary, disseminated tuberculosis, which is fatal in 10% of cases. The risk of tuberculosis is increased four-fold in patients on TNF-α antagonist therapy. The main risk factors are a history of untreated or inadequately treated primary tuberculosis, recent contact with a tuberculosis patient, and residence in or travel to a high-endemicity region. Infection surveillance agencies throughout the world have issued recommendations to ensure the detection and treatment of latent tuberculosis before TNF-α antagonist initiation. These recommendations have returned the incidence of tuberculosis to the level seen before the introduction of TNF-α antagonists. Nevertheless, there is still room for improvement. Recommendations about latent tuberculosis screening include the use of tuberculin skin tests. However, these tests are positive in individuals vaccinated with the BCG vaccine, which leads to overuse of tuberculosis chemoprophylaxis and, therefore, to unnecessary patient exposure to hepatotoxic effects. Furthermore, tuberculin skin tests may be falsely negative in immunosuppressed patients, leading to underuse of tuberculosis prophylaxis. These shortcomings of tuberculin skin tests have generated interest in interferon-gamma release assays (IGRAs). In patients with overt tuberculosis, IGRAs are more sensitive and more specific than tuberculin skin tests. However, the accuracy of IGRAs for diagnosing latent tuberculosis remains unknown, because no reference standard is available. In addition, patients taking immunosuppressant agents to treat systemic disease may exhibit anergia, which complicates the interpretation of IGRAs. Until additional data become available, caution requires that IGRAs be used only when a positive or negative result, as assessed on a case-by-case basis, will help to decide whether tuberculosis chemoprophylaxis is in order.
22002338 Lupeol, a triterpenoid isolated from Calotropis gigantea latex ameliorates the primary and 2012 Feb Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder that affects 1% of the adult population worldwide. Calotropis gigantea is a xerophytic, latex producing medicinal plant widely distributed in nature. Different parts of the plant have been traditionally used for the treatment of various ailments including arthritis. In the present study, we have isolated and characterized lupeol, a pentacyclic triterpene from the dialyzable fraction of the latex and evaluated the anti-arthritic properties of lupeol in Freund's Complete Adjuvant (FCA) induced arthritis in rats. Lupeol (50 mg/kg b.w/day) was administered orally to AA rats for 4 weeks. The alterations in body weight gain, paw volume, RBC, WBC, Hb, EPO, ESR, platelets and PCV were recorded. The activities of serum AST, ALT and ALP were also assayed. The levels of lipid profile were estimated. The levels of pro-inflammatory cytokines as well as anti-inflammatory cytokines such as TNF-α, IL-1β, IL-6 and IL-10 were also analyzed. The results of present study indicate the anti-inflammatory and anti-arthritic activity of lupeol present in the C. gigantea latex.
22833372 Granulocyte-macrophage colony-stimulating factor is a key mediator in inflammatory and art 2013 Feb OBJECTIVES: Better therapies are needed for inflammatory pain. In arthritis the relationship between joint pain, inflammation and damage is unclear. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is important for the progression of a number of inflammatory/autoimmune conditions including arthritis; clinical trials targeting its action in rheumatoid arthritis are underway. However, its contribution to inflammatory and arthritic pain is unknown. The aims of this study were to determine whether GM-CSF controls inflammatory and/or arthritic pain. METHODS: A model of inflammatory pain (complete Freund's adjuvant footpad), as well as two inflammatory arthritis models, were induced in GM-CSF(-/-) mice and development of pain (assessment of weight distribution) and arthritic disease (histology) was assessed. Pain was further assessed in a GM-CSF-driven arthritis (methylated bovine serum albumin/GM-CSF) model and the cyclooxygenase-dependence determined using indomethacin. RESULTS: GM-CSF was absolutely required for pain development in both the inflammatory pain and arthritis models, including for IL-1-dependent arthritic pain. Pain in a GM-CSF-driven arthritis model, but not the disease itself, was abolished by the cyclooxygenase inhibitor, indomethacin, indicating separate pathways downstream of GM-CSF for pain and arthritis control. CONCLUSIONS: GM-CSF is key to the development of inflammatory and arthritic pain, suggesting that pain alleviation could result from trials evaluating its role in inflammatory/autoimmune conditions.
22834652 Influence of inflammatory polyarthritis on quantitative heel ultrasound measurements. 2012 Jul 26 BACKGROUND: There are few data concerning the impact of inflammatory polyarthritis (IP) on quantitative heel ultrasound (QUS) measurements. The aims of this analysis were i) to determine the influence of IP on QUS measurements at the heel and, ii) among those with IP to determine the influence of disease related factors on these measurements. METHODS: Men and women aged 16 years and over with recent onset IP were recruited to the Norfolk Arthritis Register (NOAR). Individuals with an onset of joint symptoms between 1989 and 1999 were included in this analysis. At the baseline visit subjects underwent a standardised interview and clinical examination with blood taken for rheumatoid factor. A population-based prospective study of chronic disease (EPIC-Norfolk) independently recruited men and women aged 40 to 79 years from the same geographic area between 1993 and 1997. At a follow up assessment between 1998 and 2000 subjects in EPIC-Norfolk were invited to have quantitative ultrasound measurements of the heel (CUBA-Clinical) performed. We compared speed of sound (SOS) and broadband ultrasound attenuation (BUA), in those subjects recruited to NOAR who had ultrasound measurements performed (as part of EPIC-Norfolk) subsequent to the onset of joint symptoms with a group of age and sex matched non-IP controls who had participated in EPIC-Norfolk. Fixed effect linear regression was used to explore the influence of IP on the heel ultrasound parameters (SOS and BUA) so the association could be quantified as the mean difference in BUA and SOS between cases and controls. In those with IP, linear regression was used to examine the association between these parameters and disease related factors. RESULTS: 139 men and women with IP and 278 controls (mean age 63.2 years) were studied. Among those with IP, mean BUA was 76.3 dB/MHz and SOS 1621.8 m/s. SOS was lower among those with IP than the controls (difference = -10.0; 95% confidence interval (CI) -17.4, -2.6) though BUA was similar (difference = -1.2; 95% CI -4.5, +2.1). The difference in SOS persisted after adjusting for body mass index and steroid use. Among those with IP, disease activity as determined by the number of swollen joints at baseline, was associated with a lower SOS. In addition SOS was lower in the subgroup that satisfied the 1987 ACR criteria. By contrast, disease duration, steroid use and HAQ score were not associated with either BUA or SOS. CONCLUSIONS: In this general population derived cohort of individuals with inflammatory polyarthritis there is evidence from ultrasound of a potentially adverse effect on the skeleton. The effect appears more marked in those with active disease.
22133052 Predictors of response to rituximab in patients with active rheumatoid arthritis and inade 2011 Nov OBJECTIVES: Identifying early predictors of response to biological agents is important for both the individual patient and health economics. The aim here was to identify clinical variables that are easily assessed in clinical practice which are associated with a major response to rituximab (moderate to good EULAR response, according to DAS28 values) in patients with active rheumatoid arthritis and inadequate response to anti-TNF agents or traditional DMARDs. METHODS: Rituximab (2x1g, two weeks apart) was administered to 108 patients in four different Spanish hospitals. The primary efficacy endpoint was the percentage of patients who achieved a major response at six months. Potential predictors of a major response were identified using multivariate binary logistic regression models. RESULTS: At six months of treatment 75.9% of patients achieved a major response (24% good and 52% moderate). Comparing the clinical features at baseline between patients who did or did not achieve a major response, significant differences were found in rheumatoid factor (RF) and anti-CCP positivity, as well as in the number of failed anti-TNF agents prior to rituximab. While rituximab delivers clinical benefit in seronegative patients, the presence of RF and/or anti-CCP consistently enriches clinical responses. The multivariate analysis showed that the best model for predicting a major EULAR response to rituximab was comprised of the following two variables: the anti-CCP antibody positivity (p=0.045) and the number of previous anti-TNF agents used (p=0.028). Using a cut-off level for CCP of 300 U/ml we found that patients with an anti-CCP titre >300 U/ml were 3-4 times more likely to achieve a major EULAR response [odds ratio (OR): 3.38; 95% CI: 1.025-11.17]. By contrast, those patients who had failed to respond to 2 or more anti-TNF agents had a 72.5% lower probability of achieving a moderate to good EULAR response (OR: 0.275; 95% CI: 0.087-0.871) than did patients who had only failed to respond to one such agent. CONCLUSIONS: A lower number of previously-failed TNF blockers and high anti-CCP titre can help select the best candidates for RTX therapy in patients with RA.
22736674 Role of proopiomelanocortin-derived peptides and their receptors in the osteoarticular sys 2012 Aug Proopiomelanocortin (POMC)-derived peptides such as melanocortins and β-endorphin (β-ED) exert their pleiotropic effects via binding to melanocortin receptors (MCR) and opioid receptors (OR). There is now compelling evidence for the existence of a functional POMC system within the osteoarticular system. Accordingly, distinct cell types of the synovial tissue and bone have been identified to generate POMC-derived peptides like β-ED, ACTH, or α-MSH. MCR subtypes, especially MC1R, MC2R (the ACTH receptor), MC3R, and MC4R, but also the μ-OR and δ-OR, have been detected in various cells of the synovium, cartilage, and bone. The respective ligands of these POMC-derived peptide receptors mediate an increasing number of newly recognized biological effects in the osteoarticular system. These include bone mineralization and longitudinal growth, cell proliferation and differentiation, extracellular matrix synthesis, osteoprotection, and immunomodulation. Importantly, bone formation is also regulated by the central melanocortin system via a complex hormonal interplay with other organs and tissues involved in energy metabolism. Among the POMC-derived peptides examined in cell culture systems from osteoarticular tissue and in animal models of experimentally induced arthritis, α-MSH, ACTH, and MC3R-specific agonists appear to have the most promising antiinflammatory actions. The effects of these melanocortin peptides may be exploited in future for the treatment of patients with inflammatory and degenerative joint diseases.
23095111 Pharmacogenetic polymorphisms contributing to toxicity induced by methotrexate in the sout 2012 Nov Abstract Rheumatoid arthritis (RA) is a common illness of global significance for public health. Methotrexate (MTX) is the most broadly used disease-modifying antirheumatic drug for the treatment of RA, but it displays marked person-to-person variation in its propensity for toxicity. Several studies have suggested that polymorphisms in methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, reduced folate carrier (RFC1) G80A, and ABCB1 C3435T, could be related to methotrexate toxicity. This prospective study examined the different frequencies of MTHFR, RFC1, and ABCB1 pharmacogenetic variations between patients who have RA and those without RA. We also sought to assess the association between these polymorphisms and MTX toxicity. Four single-nucleotide polymorphisms (SNPs) were genotyped: C677T and A1298C from MTHFR, G80A from RFC1, and C3435T from ABCB1. The efficacy and toxicity of MTX were evaluated through clinical follow-up during 1 year of treatment. RA patients showed a higher frequency of the T allele at MTHFR C677T than patients without RA (p=0.049). There was a significant association between the presence of both the T allele at MTHFR C677T (p=0.006), and the C allele at ABCB1 C3435T (p=0.046), with toxicity development after 12 months of MTX treatment. However, there was no correlation between MTX toxicity and either the A allele at MTHFR A1298C or the G allele at RFC1 A80G. These data suggest that the presence of the MTHFR C677T and ABCB1 C3435T SNPs contribute to MTX toxicity in patients with RA. These observations contribute to a rapidly-growing knowledge base on the pharmacogenetics of RA and personalized medicine.
21567119 Assessment of cardiovascular risk in rheumatoid arthritis: impact of the new EULAR recomme 2012 Jan To assess the impact of the application of the European League against Rheumatism (EULAR) task force recommendations in the cardiovascular (CV) risk of a series of Spanish patients diagnosed with rheumatoid arthritis (RA). Two hundred consecutive RA patients seen at the rheumatology outpatient clinics of Bellvitge Hospital, Barcelona, were studied. Information on clinical features of the disease, classic CV risk factors, and history of CV events was assessed. Both the systematic coronary risk evaluation (SCORE) CV risk index and the modified SCORE (mSCORE) according to the last EULAR recommendations were calculated. Based on the classic CV risk factors, the mean ± standard deviation SCORE was 2.1 ± 2.3% (median, 2; interquartile range [IQR], 1-3). Twenty-three (11%) patients were above the threshold of high CV risk for the Spanish population (≥5%). Following the EULAR recommendations, a change in the score was required in 119 (59%) patients. Therefore, the mean mSCORE was 2.7 ± 2.9% (median, 2; IQR, 1-3) and, due to this, 28 (14%) patients were above the threshold of high CV risk. Nine (5%) had at least one ischemic CV event. Patients with CV events were older and had more CV risk factors and higher SCORE and mSCORE than those without CV events. Although a large proportion of patients from this series fulfilled the criteria for the application of the EULAR recommendations, the final impact on the calculated CV risk was low and clinically significant in only a few patients. However, an association between the mSCORE and the presence of ischemic CV events was observed.
21384675 [Clinical study of pneumocystis pneumonia in patients with rheumatoid arthritis]. 2011 Jan We reviewed case of pneumocystis pneumonia (PCP) with rheumatoid arthritis. We administered the antirheumatic drug methotrexate (MTX) at the time of to 13 patients, corticosteroids to 11 patients and a tumor necrosis factor (TNF) inhibitor to 3 patients. Treatment for PCP was started on admission in all cases. We administered adrenocorticosteroids to all 13 patients with a PaO2 level < 70 Torr. Three patients were under respiratory management, and 4 patients died. By univariate analysis, prognostic indicators of death were: presence of acute respiratory distress syndrome (ARDS), peripheral blood neutrophil/lymphocyte ratio, serum albumin value, serum beta-D-glucan value, and AaDO2 and PaO2/FiO2 ratios. Readministration of a TNF inhibitor in 2 patients and MTX in 3 patients was possible after PCP remission. Even though we began treatment for PCP on the day of admission, 25% of patients died. PCP may occur in patients who are given MTX or a TNF inhibitor or both, and the clinician should endeavor to detect its onset as early as possible. Elucidation of the prognostic indicators of recovery may require multivariate analysis of many cases.
22183962 Methotrexate increases expression of cell cycle checkpoint genes via JNK activation. 2012 Jun OBJECTIVE: To assess defects in expression of critical cell cycle checkpoint genes and proteins in patients with rheumatoid arthritis (RA) relative to presence or absence of methotrexate (MTX) treatment, and to investigate the role of JNK in induction of these genes by MTX. METHODS: Flow cytometric analysis was used to quantify changes in levels of intracellular proteins, measure reactive oxygen species (ROS), and determine apoptosis in different lymphoid populations. Quantitative reverse transcription-polymerase chain reaction was used to identify changes in cell cycle checkpoint target genes. RESULTS: RA patients expressed reduced baseline levels of MAPK9, TP53, CDKN1A, CDKN1B, CHEK2, and RANGAP1 messenger RNA (mRNA) and JNK total protein. The reduction in expression of mRNA for MAPK9, TP53, CDKN1A, and CDKN1B was greater in patients not receiving MTX than in those receiving low-dose MTX, with no difference in expression levels of CHEK2 and RANGAP1 mRNA between MTX-treated and non-MTX-treated patients. Further, JNK levels were inversely correlated with C-reactive protein levels in RA patients. In tissue culture, MTX induced expression of both p53 and p21 by JNK-2- and JNK-1-dependent mechanisms, respectively, while CHEK2 and RANGAP1 were not induced by MTX. MTX also induced ROS production, JNK activation, and sensitivity to apoptosis in activated T cells. Supplementation with tetrahydrobiopterin blocked these MTX-mediated effects. CONCLUSION: Our findings support the notion that MTX restores some, but not all, of the proteins contributing to cell cycle checkpoint deficiencies in RA T cells, via a JNK-dependent pathway.
24236466 Comparative effectiveness of biologic antirheumatic therapies in rheumatoid arthritis afte 2012 Nov Evaluation of: Gomez-Reino JJ, Maneiro JR, Ruiz J et al. Comparative effectiveness of switching to alternative tumour necrosis factor (TNF) antagonists versus switching to rituximab in patients with rheumatoid arthritis who failed previous TNF antagonists: the MIRAR Study. Ann. Rheum. Dis. doi:10.1136/annrheumdis-2012-201324 (2012) (Epub ahead of print). Rheumatoid arthritis is a chronic immune-mediated disease affecting approximately 1% of the population. The prognosis of this chronic condition has considerably improved over the past decade with the earlier use of antirheumatic drugs and the introduction of new biologic therapies. Current treatment guidelines recommend using these agents after a failed response to conventional disease-modifying antirheumatic drugs, but the relative positioning of the various available biologic agents is not yet well established. All biologic agents have been proven to be superior to placebo in large trials, but only very few randomized controlled trials have compared directly competing therapeutic options. This article evaluates the effectiveness of rituximab compared with an alternative TNF antagonist (anti-TNF) in rheumatoid arthritis patients who experienced a previous failed response to anti-TNF. The results of this large observational cohort study suggest that rituximab offers a greater benefit on rheumatoid arthritis disease activity than alternative monoclonal anti-TNFs.
22113646 Use of general practice and rheumatology outpatient services in rheumatoid arthritis. 2012 Aug BACKGROUND: Patients with rheumatoid arthritis (RA) should be treated in close cooperation between GPs and rheumatologists and following treatment guidelines. In this study, we analyse the utilization of health care among patients with RA and explain the determinants of the frequency of use of GP and rheumatologist services. METHODS: A random sample (n = 1259) of adult Estonian patients with RA was investigated in 2007. A pre-structured questionnaire included questions regarding respondents' socio-economic status, quality of life, self-reported use of health care, time, distance and financial aspects of access to health care. The impact of the variables on the frequency of use of health care was analysed with regression analysis. RESULTS: Use of GP services was higher among people who lived outside the capital, had more health problems and experienced disability due to their RA. Time and distance limits had an effect on the frequency of use of both primary and specialist care. A shorter waiting time to the GP and a longer waiting time to the rheumatologist were associated with more frequent use of GP services, but a shorter waiting time to the rheumatologist was related to more frequent visits to the rheumatologist. Patient's costs were not associated with the frequency of health care use. CONCLUSIONS: Use of health care among people with RA depends primarily upon doctors' waiting times, patients' place of residence and their health status. The GP has a significant role in the management of RA patients, especially for those who have multiple health problems and those living in rural areas.
21814754 Rheumatoid factor and antibodies against citrullinated peptides in Moroccan patients with 2012 Feb We aimed to evaluate the immunological status and its relationships with disease-related parameters of activity, severity and quality of life in Moroccan patients with rheumatoid arthritis (RA). Two hundred forty-five consecutive patients with RA were recruited. The following data were collected: demographic characteristics, disease duration (years), disease activity (evaluated by the disease activity score, DAS28), structural damage (evaluated by Sharp's method as modified by van der Heijde), functional disability (assessed by using the Moroccan version of the Health Assessment Questionnaire, HAQ) and quality of life (by using the Arabic version of the Medical Outcomes Study Short Form 36 Health Survey: the SF-36). Immunological status (rheumatoid factor rate, RF) and antibodies against citrullinated peptides rate (ACPAs) by the Elisa method were examined. ACPAs were detected in 75.1% of patients with a mean rate of 79.2 ± 43.8 UI. RF was detected in 80.8% of patients with a mean rate of 80.1 ± 50.6 UI. Patients with positive RF and ACPAs had higher disease activity, impaired functional ability, severe structural damage, more ocular symptoms and altered aspects of quality of life. In univariate analysis, higher levels of ACPAs were significantly correlated with the age at onset (r = 0.307), disease duration (r = 0.520), disease activity (DAS28) (r = 0.531), Sharp score (r = 0.431), and with the deterioration of all domains of SF-36 (for all p ≤ 0.01). RF levels were correlated with disease duration (r = 0.517), disease activity (r = 0.470), functional disability (r = 0.521), and the alteration of physical domains of SF-36 (for all p ≤ 0.01). In multivariate analysis, the main factors associated to ACPAs and RF levels were functional disability, structural damage and impaired QoL. Furthermore, using the SF-36 scores as dependent variables, the impairment of physical domains and the domain of vitality were significantly associated with ACPA levels while the decrease of the domain of physical function was associated with the level of RF. Our study suggests that the presence and the levels of ACPAs and RF in our RA patients are associated with more active disease, more severe joint damage, worst functional disability and altered aspects of quality of life.
21885512 Update on research and future directions of the OMERACT MRI inflammatory arthritis group. 2011 Sep The OMERACT Magnetic Resonance Imaging (MRI) Task Force has developed and evolved the psoriatic arthritis MRI score (PsAMRIS) over the last few years, and at OMERACT 10, presented longitudinal evaluation by multiple readers, using PsA datasets obtained from extremity MRI magnets. Further evaluation of this score will require more PsA imaging datasets. As well, due to improved image resolution since the development of the original rheumatoid arthritis MRI scoring system (RAMRIS), the Task Force has worked on semiquantitative assessment of joint space narrowing, and developed a reliable method as a potential RAMRIS addendum, although responsiveness will need to be evaluated. One of the strengths of MRI is the ability to detect subclinical synovitis, so the group worked on obtaining low disease activity/clinical remission datasets from a number of international centers and presented cross-sectional findings. Subsequent longitudinal evaluation of this unique resource will be a major continuing focus for the group.
22569293 Expression of the non-neuronal cholinergic system in human knee synovial tissue from patie 2012 Nov 27 AIMS: As the stimulation of the α7-nicotinic acetylcholine receptor (nAChR), which is present in the synovium of patients with rheumatoid arthritis (RA), leads to a decrease in pro-inflammatory cytokines, the α7-nAChR is being discussed as a new therapeutic target. On this background we addressed the question whether α7-nAChR mRNA was differentially expressed in RA compared to osteoarthritis (OA) synovial samples and whether other components of the non-neuronal cholinergic system were also present and differentially expressed in the synovium of patients with RA in comparison to OA. MAIN METHODS: The expression of nicotinic and muscarinic acetylcholine receptors (mAChRs), choline and acetylcholine transporters, synthesising and degrading enzymes was determined in human samples of synovial tissue from patients with RA and OA using RT-PCR and immunofluorescence labelling. KEY FINDINGS: Compared to OA, patients with RA showed increased expression of nAChR subunit β4 while a decline in subunits α2 and α4 as well as in mAChR M1R was observed. For all other nAChR subunits and mAChRs however there was no significant difference between RA and OA patients. With regard to the ACh transporters and enzymes no expressional changes were observed between OA and RA patients, except for the choline acetyltransferase (ChAT) which was only detected in OA but not in RA synovium. SIGNIFICANCE: Our results indicate that besides α7-nAChR other components of the non-neuronal cholinergic system are present and differentially expressed in the synovium of RA and OA patients, which makes them interesting alternative targets in the development of new strategies for RA therapy.
21174621 The effect of ESR1 and ESR2 gene polymorphisms on the outcome of rheumatoid arthritis trea 2011 Jan AIM: Leflunomide is the drug used in the therapy for rheumatoid arthritis (RA). Previous studies indicated that the efficacy of the therapy with antirheumatic drugs is more effective in men than in women. Moreover, estrogens can decrease the anti-inflammatory action of leflunomide. Estrogens act through the estrogen receptors ESR1 and ESR2. In ESR1 and ESR2 genes, several polymorphisms have been detected. The aim of the present study was to examine the association between polymorphisms in the ESR1 and ESR2 genes and the response to treatment of RA patients with leflunomide. MATERIALS & METHODS: The study was carried out on 115 women, mean age 54.1 ± 11.0 years, diagnosed with RA and treated with leflunomide (20 mg daily). RESULTS: Our results indicated a better response to treatment in patients with ESR1 rs9340799 AA and rs2234693 TT genotypes after 12 months of therapy. In these patients, the improvement of erythrocyte sedimentation rate, patient's global assessment of disease activity on a 100 mm visual analog scale and disease activity score values was greater than in patients with other genotypes. The ESR1 rs9340799-rs2234693 A-T haplotype was associated with a better response to treatment, the G-C haplotype with a worse response and the A-C haplotype was neutral. There were no statistically significant associations of response to treatment with ESR2 gene rs4986938 and rs1256049 polymorphisms. CONCLUSION: The results of the present study suggest that ESR1 gene polymorphisms in females with RA may be associated with the response to treatment with leflunomide.