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ID PMID Title PublicationDate abstract
20300947 Detection of bone erosion in early rheumatoid arthritis: ultrasonography and conventional 2010 Aug Nowadays, there is a trend toward early diagnosis and treatment of rheumatoid arthritis (RA) especially in patients with early signs of bone erosion which can be detected by magnetic resonance imaging (MRI). The aim of following study is to compare the sensitivity and specificity of ultrasonography (US) and conventional radiography (CR) compared to MRI for early detection of bone erosion in RA patients. In 12 patients with RA diagnosis, 120 first to fifth metacarpophalangeal joints and 96 second to fifth proximal interphalangeal joints were examined. Non-contrast MRI, US and CR were performed for bone erosion evaluation. For further analysis, the patients were divided in two equal groups according to disease activity score (DAS28). The overall sensitivity and specificity of US compared to MRI in detecting bone erosion were 0.63 and 0.98, respectively with a considerable agreement (kappa = 0.68, p < 0.001). Sensitivity and specificity of CR compared to MRI in detecting bone erosion were 0.13 and 1.00, respectively (kappa = 0.20, p < 0.001). In patients with more active disease, the sensitivity and specificity were 0.67 and 0.99 (kappa = 0.74, p < 0.001) compared to 0.59 and 0.97 (kappa = 0.61, p < 0.001) for the rest of patients according to DAS28. Conclusively, these findings reveal an acceptable agreement between US and MRI for detection of bone erosion in patients with early RA but not CR. US might be considered as a valuable tool for early detection of bone erosion especially when MRI is not available or affordable. Besides, it seems the US could be more reliable when the disease is more active.
20615160 Prevalence and predictive factors of comorbidity in rheumatoid arthritis patients monitore 2010 OBJECTIVES: To study the prevalence of comorbid conditions at diagnosis and during follow-up in a cohort of patients with early rheumatoid arthritis (RA) followed prospectively over 20 years, and to identify possible early predictive factors for future comorbidities. METHODS: A community-based cohort of 183 patients (mean age 52 years, 63% female) with early RA was recruited between 1985 and 1989. The presence of comorbidity at RA diagnosis and the occurrence of additional comorbidities were recorded continuously. Possible predictors of future comorbidities were analysed using the Cox proportional hazards model. RESULTS: At RA diagnosis, at least one comorbid condition was present in 43% of the patients. Cardiovascular diseases (CVDs), including hypertension (16% of patients) and malignancy (6% of patients), were most common. In total, 82% of patients developed additional comorbidities during follow-up. CVD and malignancies remained the most frequent comorbidities. Higher age [p < 0.001, odds ratio (OR) 1.03, 95% confidence interval (CI) 1.01–1.15] and the presence of any comorbidity at diagnosis (p = 0.02; OR 1.64, 95% CI 1.08–2.52) predicted future comorbidity. Measures of inflammation at diagnosis or during follow-up were not predictive for development of CVD. CONCLUSION: Comorbidity was present in a considerable proportion of patients in this cohort. More than 40% of patients had another disease at inclusion and during follow-up and > 80% developed additional conditions. The pattern of comorbidity remained unchanged, with CVD and malignancy being most common. Older age and the presence of comorbidity at RA diagnosis predicted the development of comorbidities. The degree of inflammation at any time point was not predictive of future CVD.
20401725 Association analysis of TNFR2, VDR, A2M, GSTT1, GSTM1, and ACE genes with rheumatoid arthr 2011 Oct Genetic associations of TNFR2, VDR (Bsm I and Fok I), A2M, GSTT(1), GSTM(1) and ACE in South Asian and Caucasian patients with rheumatoid arthritis (RA) were assessed in this study. DNA samples from South Asians (134 cases, 149 controls) and Caucasians (137 cases, 150 controls) from the East Midlands of the United Kingdom were genotyped for seven polymorphisms. All cases were rheumatoid-factor positive. Significant genetic associations were observed with TNFR2 R-R (OR = 3.16, CI 1.20-9.26, P < 0.05), A2M 1-1 (OR = 2.09, CI 1.21-3.64, P < 0.05) and GST T(1)null (OR = 1.97, CI 1.07-3.68, P < 0.05) among Caucasian patients. In South Asians, VDR Bsm I B-B genotype (OR = 2.08, CI 1.23-3.52, P < 0.05), A2M 2-2 genotype (OR = 3.99, CI 1.19-17.18, P < 0.05), and GST T(1)null genotype (OR = 2.81, CI 1.40-5.77, P < 0.002) genotypes were associated with RA. In the majority of cases, recessive and multiplicative modes of inheritance explained the observed associations. This study demonstrates that ethnicity affects the genetic associations in RA.
19359776 Usefulness of anti -CCP antibodies in rheumatic diseases in Indian patients. 2009 Mar BACKGROUND: The usefulness of anti-cyclic citrullinated peptide antibodies (anti-CCP antibodies) to identify rheumatic arthritis (RA) from other rheumatic diseases presenting with joint pain is not well studied. AIMS: We aimed to determine the sensitivity and specificity of anti-CCP antibodies in Indian RA patients with respect to non-RA rheumatic diseases and to study the relationship of anti-CCP antibodies and IgG, IgM and IgA rheumatoid factor in RA. SETTINGS AND DESIGN: Case-control cross-sectional study carried out in the rheumatology division of All India Institute of Medical Sciences. MATERIALS AND METHODS: Sixty-three patients with rheumatoid arthritis (RA) and 51 patients with non-RA rheumatic diseases having joint pain were included in the study. Sera were tested for anti-CCP antibodies (IgG) and IgA, IgM, IgG rheumatoid factor, using a commercially available enzyme-linked immunosorbent assay. STATISTICAL ANALYSIS: Statistical analysis was performed using SPSS statistical software version 11.5. RESULTS: Fifty-four of 63 RA patients (85.71%) were positive for anti-CCP antibodies. In the non-RA group, anti-CCP antibody was positive in only 5 of 51 patients (9.8%). Our study found a sensitivity of 85% and a specificity of 90.19% with regard to the use of anti-CCP antibodies assay in patients with joint pain to correctly identify RA. Anti-CCP antibodies positive patients did not have more erosive disease. IgM-RF-positive patients had more erosion when compared to the IgM-RF-negative group. Thirty-two of 57 (56.1%) IgM-RF-positive patients had erosions, while no patient (0/6 patients) had erosions in the IgM-RF-negative group (P=0.01) CONCLUSION: Anti-CCP antibodies have high sensitivity and specificity for diagnosis of RA, in Indian patients. Anti-CCP antibodies positive patients did not have more erosive disease in our study.
19918042 Is fatigue an inflammatory variable in rheumatoid arthritis (RA)? Analyses of fatigue in R 2009 Dec OBJECTIVE: To investigate whether fatigue is an inflammatory (rheumatoid arthritis; RA) variable, the contributions of RA variables to fatigue, and the levels of fatigue in RA compared with osteoarthritis (OA) and fibromyalgia (FM). METHODS: We studied 2096 RA patients, 1440 with OA, and 1073 with FM in a clinical setting, and 14,607 RA, 3173 OA, and 2487 patients with FM in survey research. We partitioned variables into inflammatory and noninflammatory factors and examined variable contribution to fatigue (0-10 visual analog scale). RESULTS: Factor analysis identified Disease Activity Score-28 (DAS28) and swollen (SJC) and tender joint count (TJC) as a physician-inflammation factor, and patient global assessment, pain, Health Assessment Questionnaire, and fatigue as patient components. Fatigue demonstrated weak correlations with erythrocyte sedimentation rate (ESR; r = 0.071) and SJC (r = 0.112), weak to fair correlations with TJC (r = 0.294), physician global assessment of RA activity (r = 0.384), and DAS28 (r = 0.399), but strong correlation with patient global assessment of severity (r = 0.567). In hierarchical regression analysis, patient global explained 43.1% of DAS28 fatigue variance; when SJC, TJC, and ESR were entered, the explained variance increased to 43.7%. In reverse order, SJC, TJC, and ESR explained 9.2% of the variance, but explained variance increased to 43.7% when patient global was added. The mean clinic fatigue scores were RA 4.9, OA 4.8, FM 7.6; mean survey scores were RA 4.5, OA 4.4, FM 6.3. Adjusted for age and sex, RA and OA fatigue scores were not significantly different. CONCLUSION: Inflammatory components of the DAS28 contribute minimally to fatigue. RA and OA fatigue levels do not differ. Fatigue is not an inflammatory variable and has no unique association with RA or RA therapy.
19497915 Effect of the oral application of a highly selective MMP-13 inhibitor in three different a 2010 May OBJECTIVE: To evaluate the decrease of cartilage destruction by a novel orally active and specific matrix metalloproteinase 13 (MMP-13) inhibitor in three different animal models of rheumatoid arthritis (RA). MATERIALS AND METHODS: The SCID mouse co-implantation model of RA, the collagen-induced arthritis (CIA) model in mice and the antigen-induced arthritis model (AIA) in rabbits were used. RESULTS: In the SCID mouse co-implantation model, the MMP-13 inhibitor reduced cartilage destruction by 75%. In the CIA model of RA, the MMP-13 inhibitor resulted in a significant and dose-dependent decrease in clinical symptoms as well as of cartilage erosion by 38% (30 mg/kg), 28% (10 mg/kg) and 21% (3 mg/kg). No significant effects were seen in the AIA model. No toxic effects were seen in all three animal models. CONCLUSION: Although several MMPs in concert with other proteinases have a role in the process of cartilage destruction, there is a need for highly selective MMP inhibitors to reduce severe side effects that occur with non-specific inhibitors. Significant inhibition of MMP-13 reduced cartilage erosions in two of three tested animal models of RA. These results strongly support the development of this class of drugs to reduce or halt joint destruction in patients with RA.
20506561 Performance of rheumatoid arthritis disease activity measures and juvenile arthritis disea 2010 Aug OBJECTIVE: To measure the abilities of the continuous measures of disease activity used in rheumatoid arthritis (RA) and the 3 versions of the Juvenile Arthritis Disease Activity Score (JADAS; based upon 10-, 27-, and 71-joint counts) to accurately classify the American College of Rheumatology (ACR) pediatric measures of response, flare, and inactive disease in polyarticular-course juvenile idiopathic arthritis (JIA). METHODS: We conducted a secondary analysis of a randomized trial of infliximab in polyarticular-course JIA. Disease activity was calculated at baseline and weeks 14, 28, and 52 using the Disease Activity Score (DAS), DAS in 28 joints, Simplified Disease Activity Index, Clinical Disease Activity Index, and JADAS. The ability of the RA measures and JADAS to classify each ACR pediatric measure, flare, and inactive disease was measured by areas under the receiver operating characteristic curve (AUCs). Positive predictive values (PPVs) for inactive disease were calculated. RESULTS: Data from 97 participants were available. The AUCs for the RA scores for each ACR pediatric measure were 0.73-0.89. The AUCs of the JADAS for the ACR pediatric measures were 0.75-0.92. The PPVs of the RA scores for inactive disease were 0.33-0.67. The PPVs of the JADAS for inactive disease were each 0.93. Based on the RA and JADAS scores, the percentage of visits misclassified as inactive disease ranged from 7-67%. CONCLUSION: The RA measures and JADAS versions showed acceptable to excellent ability to classify participants for each pediatric outcome measure, but the clinical significance of differences between AUCs for these scores could not be assessed. Misclassification of active disease versus inactive disease by the RA and JADAS scores was not uncommon in this cohort.
20979550 Certolizumab pegol: a new biologic targeting rheumatoid arthritis. 2010 Nov The past decade has been an exciting period for clinical research and patient care in rheumatoid arthritis. This is mostly due to targeted biologic agents that have changed the outcome of this disease. Certolizumab pegol (Cimzia(®), UCB Inc., GA, USA), which targets TNF-α with a different mechanism of action than widely used biologics, was initially investigated for Crohn's disease but has now been shown to be effective for rheumatoid arthritis. There have been three significant clinical trials demonstrating the efficacy of certolizumab pegol in active rheumatoid arthritis; two with combination methotrexate and one with monotherapy. This article will summarize the data from those trials and compare some of the characteristics of certolizumab pegol to conventional disease-modifying antirheumatic drugs and other biologic agents. Treatment recommendations are beyond the scope of this review; however, with many options available, there will be annotations on current trends in the care of this chronic disease.
21061459 The anti-arthritic effects of synthetic melittin on the complete Freund's adjuvant-induced 2010 Bee venom (BV) has been used for millennia in Chinese traditional medicine to treat rheumatoid arthritis (RA). However, its components and mechanism remain unclear, which has hampered its development and application for the treatment of RA. In this study, we examined the anti-arthritis effects of melittin, which composes nearly 50% of the dry weight of whole BV, on the complete Freund's adjuvant-induced (CFA-induced) RA model in rats. The RA animal models were treated with solutions of BV, melittin, and saline by injection into a specific acupoint (Zusanli). The BV and melittin treatments statistically diminished the thickness of the arthroses in the injected side of the paw, compared to the saline treatment. Melittin therapy also significantly reduced arthritis-induced nociceptive behaviors, as assessed by the thermal hyperalgesia test. In addition, CFA-induced Fos expression in the superficial layer of the lumbar spinal cord was significantly suppressed by the BV and melittin treatments, compared to the saline treatment. These results indicate that melittin is an effective anti-arthritis component of whole bee venom, making it a promising candidate as an anti-arthritis drug.
19411391 The value of HLA-DRB1 shared epitope, -308 tumor necrosis factor-alpha gene promoter polym 2009 Jun OBJECTIVE: To study the value of HLA-DRB1 shared epitope (SE), -308 tumor necrosis factor-alpha (TNF-alpha) gene promoter polymorphism, rheumatoid factor (RF), anti-citrullinated peptide antibodies (anti-CCP), and baseline erosions for predicting radiological outcome at 1 year in patients with recent-onset rheumatoid arthritis (RA). METHODS: Radiological damage was assessed by radiographs at baseline and at 1 year in an inception cohort of 134 RA patients with disease duration
19955056 Bone marrow edema is the most specific finding for rheumatoid arthritis (RA) on noncontras 2010 Feb OBJECTIVE: To evaluate the sensitivity and specificity of magnetic resonance imaging (MRI) in detecting erosions, bone edema, and synovitis in the metacarpophalangeal and wrist joints for rheumatoid arthritis (RA). METHODS: MRI scans of bilateral hands and wrists of 40 healthy subjects and 40 RA patients were performed using 0.2 T extremity-MRI and read blindly using a modified RA MRI (RAMRIS) system (no contrast injection, imaging in 1 plane only). To determine interreader reliability, images of 10 randomly selected subjects were read independently by a musculoskeletal radiologist. RESULTS: A total of 3360 bones were evaluated. Patients with RA had significantly more erosions as well as higher scores for bone edema and synovitis than healthy subjects. Age had a significant effect on the number of erosions in both groups. However, when disease duration was factored in, age became insignificant in RA patients. Erosion number correlated with positive rheumatoid factor and higher C-reactive protein values. The intraclass correlation coefficient between the 2 readers was 0.76 for individual joints and 0.88 for total scores. When having a single erosion was used as a positive test for RA, the sensitivity of this test was 90%, but the specificity was only 35%. Presence of bone edema provided 65% sensitivity and 82.5% specificity. Eliminating the lunate from scoring for bone edema increased the specificity to 87.5% while decreasing the sensitivity to 62.5%. CONCLUSION: While MRI is a highly sensitive tool for identifying and tracking the progression of erosions, erosions detected by MRI with measures commonly used in a rheumatologist's office (no contrast, imaging in 1 plane) provide low specificity for RA. Bone marrow edema is the most specific MRI lesion for RA in this setting.
19252376 [A review for recent advances in AA amyloid research and therapeutic approach to AA amyloi 2009 Feb AA amyloidosis is a life threatening clinical complication of chronic inflammatory diseases such as rheumatoid arthritis. It has been demonstrated biochemically that amyloidosis resulted from abnormal folding of proteins, which are deposited as insoluble fibrils in extracellular tissue, leading to the disruption of their normal function. In this regard, amyloidosis has been recognized as a conformation disorder. Interestingly, genetic polymorphisms of amyloid precursor protein (SAA) have been reported to associate with increased risk for AA amyloidosis. Also recent biochemical research revealed that SAA is synthesized under the influence of the proinflammatory cytokines, such as IL-6, TNF-alpha, IL-1. Additionally, it was suggested that amyloid deposits in extracellular tissue could reflect to the serum level of SAA in the reversible fashion, leading to the hypothesis that the control of the SAA synthesis could be beneficial to the treatment of amyloidosis. In this context, anti-cytokine therapies may be most effective. Especially the inhibition of IL-6 is critical to suppression of SAA production, so treatment with a humanized monoclonal antibody against human IL-6 receptor may not only ameliorate RA disease activity but also pave the way for the treatment of AA amyloidosis.
19460147 Different properties of ACPA and IgM-RF derived from a large dataset: further evidence of 2009 INTRODUCTION: The aim of this study was to examine seroconversion and the relationship with age and inflammation of autoantibodies in a large group of patients attending an outpatient rheumatology clinic. METHODS: Levels of antibodies to citrullinated proteins/peptides (ACPAs) and IgM rheumatoid factor (IgM-RF) were determined in 22,427 samples collected from 18,658 patients. The diagnosis was derived from a diagnosis registration system. The degree of seroconversion in repeated samples and the correlation of levels with age and inflammatory markers were determined for ACPA and IgM-RF in rheumatoid arthritis (RA) and non-RA patients. RESULTS: Seventy-one percent of RA patients (n = 1,524) were ACPA-positive and 53% were IgM-RF-positive; in non-RA patients (n = 2,245), the corresponding values were 2% and 4%, respectively. In patients with at least two samples (n = 3,769), ACPA status was more stable than IgM-RF status in RA patients. ACPA- or IgM-RF-negative non-RA patients seldom became positive. ACPA positivity was unrelated to age in both RA and non-RA patients. IgM-RF positivity was unrelated to age in RA patients; however, it increased with age in non-RA patients. The correlation between autoantibody levels and inflammatory markers was low in general and was somewhat higher for IgM-RF than for ACPA. CONCLUSIONS: ACPA status is more stable in time and with increasing age than IgM-RF status, further establishing its role as a disease-specific marker. ACPA and IgM-RF levels are only moderately correlated with markers of inflammation.
19151030 Genetics of bone loss in rheumatoid arthritis--role of vitamin D receptor polymorphisms. 2009 Apr RA is a systemic inflammatory arthritis that leads to local and systemic bone loss. Osteoporosis or the systemic bone loss associated with RA increases the risk for fragility fractures, which can affect quality of life dramatically in RA patients. Although traditional and RA-related risk factors have been defined and studied for osteoporosis associated with RA, genetic factors such as polymorphic variants in the traditional candidate genes for osteoporosis, such as the vitamin D receptor (VDR), type 1 collagen A1 (COLIA1) and oestrogen receptor-alpha (ESR1), have not been well elucidated in RA patients. This review summarizes the currently available literature on the association of VDR polymorphisms with local and systemic bone loss in RA. It also discusses potential targets for genetic research in this area, such as polymorphisms in genes, such as IL-6 (IL6) and TNF receptor type 2 (TNFRSF1B), which control the inflammatory response in RA and may influence bone loss in RA. Defining such genetic factors, in addition to traditional and RA-related risk factors for osteoporosis in RA, may facilitate early identification of patients at high risk for fractures who can then be targeted for treatment.
20498217 Increased prevalence of diastolic dysfunction in rheumatoid arthritis. 2010 Sep OBJECTIVE: To compare the prevalence of left ventricular (LV) diastolic dysfunction in subjects with and without rheumatoid arthritis (RA), among those with no history of heart failure (HF), and to determine risk factors for diastolic dysfunction in RA. METHODS: A cross-sectional, community-based study comparing cohorts of adults with and without RA and without a history of HF was carried out. Standard two-dimensional/Doppler echocardiography was performed in all participants. Diastolic dysfunction was defined as impaired relaxation (with or without increased filling pressures) or advanced reduction in compliance or reversible or fixed restrictive filling. RESULTS: The study included 244 subjects with RA and 1448 non-RA subjects. Mean age was 60.5 years in the RA cohort (71% female) and 64.9 years (50% female) in the non-RA cohort. The vast majority (>98%) of both cohorts had preserved ejection fraction (EF> or =50%). Diastolic dysfunction was more common in subjects with RA at 31% compared with 26% (age and sex adjusted) in non-RA subjects (OR=1.6; 95% CI 1.2 to 2.4). Patients with RA had significantly lower LV mass, higher pulmonary arterial pressure and higher left atrial volume index than non-RA subjects. RA duration and interleukin 6 (IL-6) level were independently associated with diastolic dysfunction in RA even after adjustment for cardiovascular risk factors. CONCLUSION: Subjects with RA have a higher prevalence of diastolic dysfunction than those without RA. RA duration and IL-6 are independently associated with diastolic dysfunction, suggesting the impact of chronic autoimmune inflammation on myocardial function in RA. Clinical implications of these findings require further investigation.
19151010 Gene-environment interaction between HLA-DRB1 shared epitope and heavy cigarette smoking i 2010 Jan BACKGROUND: Previous studies have reported an interaction between ever cigarette smoking and the presence of the human leukocyte antigen (HLA)-DRB1 shared epitope (SE) genotype and rheumatoid arthritis (RA) risk. To address the effect of dosage, a case-control study nested within two prospective cohorts to determine the interaction between heavy smoking and the HLA-SE was conducted. METHODS: Blood was obtained from 32 826 women in the Nurses' Health Study and 29 611 women in the Nurses' Health Study II. Incident RA diagnoses were validated by chart review. Controls were matched for age, menopausal status and postmenopausal hormone use. High-resolution HLA-DRB1 genotyping was performed for SE alleles. HLA-SE, smoking, HLA-SE* smoking interactions and RA risk, were assessed using conditional logistic regression models, adjusted for age and reproductive factors. Additive and multiplicative interactions were tested. RESULTS: In all, 439 Caucasian matched pairs were included. Mean age at RA diagnosis was 55.2 years; 62% of cases were seropositive. A modest additive interaction was observed between ever smoking and HLA-SE in seropositive RA risk. A strong additive interaction (attributable proportion due to interaction (AP) = 0.50; p<0.001) and significant multiplicative interaction (p = 0.05) were found between heavy smoking (>10 pack-years) and any HLA-SE in seropositive RA risk. The highest risk was in heavy smokers with double copy HLA-SE (odds ratio (OR) 7.47, 95% CI 2.77 to 20.11). CONCLUSIONS: A strong gene-environment interaction was observed between HLA-SE and smoking when stratifying by pack-years of smoking rather than by ever smoking. Future studies should assess cumulative exposure to cigarette smoke when testing for gene-smoking interactions.
20843910 Canadian variation by province in rheumatoid arthritis initiating anti-tumor necrosis fact 2010 Dec OBJECTIVE: We compared variations among Canadian provinces in rheumatoid arthritis (RA) initiating anti-tumor necrosis factor (TNF) therapy. METHODS: Data were obtained from the Optimization of Humira trial (OH) and from the Ontario Biologics Research Initiative (OBRI). Baseline characteristics were compared between regions: Ontario (ON), Quebec (QC), and other provinces (OTH). We compared Ontario OH to OBRI patients who were initiating anti-TNF therapy. RESULTS: In 300 OH patients, mean age was 54.8 years (13.3). There were 151 (50.3%) ON patients, 57 from QC (19%), and 92 from OTH (30.7%). Regional differences were seen in the number of disease-modifying antirheumatic drugs (DMARD) ever taken (ON: 3.8 ± 1.4, QC: 3.1 ± 1.1, OTH: 3.3 ± 1.4; p < 0.001); swollen joint count (SJC; ON: 10.9 ± 5.9, QC: 9.0 ± 4.4, OTH: 11.3 ± 5.6; p = 0.033); tender joint count (TJC; ON: 12.2 ± 7.5, QC: 10.3 ± 5.7, OTH: 14.4 ± 7.6; p = 0.003); 28-joint Disease Activity Score (DAS28; ON: 5.8 ± 1.2, QC: 5.6 ± 1.0, OTH: 6.0 ± 1.1; p = 0.076); and Health Assessment Questionnaire (ON: 1.4 ± 0.7, QC: 1.7 ± 0.7, OTH: 1.5 ± 0.7; p = 0.060). DMARD-ever use differed: methotrexate (ON: 94.7%, QC: 93%, OTH: 84.8%; p = 0.025); leflunomide (ON: 74.8%, QC: 21.1%, OTH: 51.1%; p < 0.001); sulfasalazine (ON: 51%, QC: 38.6%, OTH: 25%; p < 0.001); myochrysine (ON: 9.3%, QC: 0%, OTH: 15.2%; p = 0.008); and hydroxychloroquine (ON: 67.5%, QC: 86%, OTH: 66.3%; p = 0.018). In comparison to ON OH patients, 95 OBRI patients initiating first anti-TNF had lower SJC (p = 0.017), TJC (p = 0.008), and DAS28 (p = 0.05). CONCLUSION: In Quebec, where access to anti-TNF is less restrictive, patients had lower SJC and TJC. ON used more DMARD, especially leflunomide, as mandated by the provincial government. Both provincial funding criteria and prescribing habits may contribute to differences. Canadian rheumatologists may vary in treatment decisions, but patients generally have similar DAS28 when initiating anti-TNF therapy.
20039433 Novel role of plasmacytoid dendritic cells in humans: induction of interleukin-10-producin 2010 Jan OBJECTIVE: Reestablishing immune tolerance and long-term suppression of disease represent major therapeutic goals in rheumatoid arthritis (RA). Dendritic cells (DCs) likely play a central role in such regulation via the expansion and/or induction of Treg cells. The present study was undertaken to explore the contribution of DCs to the development of Treg cells in a human autoimmune disease setting. METHODS: DC subsets were characterized by flow cytometry in the peripheral blood and synovial fluid of patients with RA. Proliferation of and cytokine release by naive CD4+CD25- T cells were measured in cocultures of these cells with DCs from patients with RA and healthy controls. The suppressive capacity of DC-polarized T cells was explored in vitro by a standard suppression assay. RESULTS: Only very low numbers of both plasmacytoid DCs (CD303+) and myeloid DCs (CD1c+) were present in the peripheral blood of patients with active RA. In contrast, patients with therapy-induced remission of RA exhibited higher numbers of circulating plasmacytoid DCs. Mature plasmacytoid DCs from RA patients with low disease activity, but not those from healthy controls, expressed high levels of indoleamine 2,3-dioxygenase and promoted the differentiation of allogeneic naive CD4+CD25- T cells into interleukin-10-secreting Treg cells, or Tr1 cells, that showed poor proliferation in vitro. Importantly, these plasmacytoid DC-primed Treg cells potently suppressed the proliferation of autologous naive CD4+ T cells, in a dose-dependent manner. CONCLUSION: These results demonstrate, for the first time, that human plasmacytoid DCs may be educated within the rheumatoid microenvironment to acquire a tolerogenic phenotype. Modulation of the immune response by plasmacytoid DCs might provide novel immune-based therapies in autoimmunity and transplantation.
19644859 Association of a single-nucleotide polymorphism in CD40 with the rate of joint destruction 2009 Aug OBJECTIVE: The severity of joint destruction in rheumatoid arthritis (RA) is highly variable from patient to patient and is influenced by genetic factors. Genome-wide association studies have enormously boosted the field of the genetics of RA susceptibility, but risk loci for RA severity remain poorly defined. A recent meta-analysis of genome-wide association studies identified 6 genetic regions for susceptibility to autoantibody-positive RA: CD40, KIF5A/PIP4K2C, CDK6, CCL21, PRKCQ, and MMEL1/TNFRSF14. The purpose of this study was to investigate whether these newly described genetic regions are associated with the rate of joint destruction. METHODS: RA patients enrolled in the Leiden Early Arthritis Clinic were studied (n=563). Yearly radiographs were scored using the Sharp/van der Heijde method (median followup 5 years; maximum followup 9 years). The rate of joint destruction between genotype groups was compared using a linear mixed model, correcting for age, sex, and treatment strategies. A total of 393 anti-citrullinated protein antibody (ACPA)-positive RA patients from the North American Rheumatoid Arthritis Consortium (NARAC) who had radiographic data available were used for the replication study. RESULTS: The TT and CC/CG genotypes of 2 single-nucleotide polymorphisms, rs4810485 (CD40) and rs42041 (CDK6), respectively, were associated with a higher rate of joint destruction in ACPA-positive RA patients (P=0.003 and P=0.012, respectively), with rs4810485 being significant after Bonferroni correction for multiple testing. The association of the CD40 minor allele with the rate of radiographic progression was replicated in the NARAC cohort (P=0.021). CONCLUSION: A polymorphism in the CD40 locus is associated with the rate of joint destruction in patients with ACPA-positive RA. Our findings provide one of the first non-HLA-related genetic severity factors that has been replicated.
19590439 Evaluation of the internet for finding persons with undiagnosed rheumatoid arthritis and s 2009 Aug BACKGROUND: The internet is used by many new rheumatology patients before visiting a health care provider, and is also used for health education, for recruiting study participants, administering surveys, conducting clinical trials, data entry and management of multicenter trials, and providing a forum for patients to share experiences in chat rooms. The internet has not been used for nor evaluated for public health applications. OBJECTIVES: We evaluated the internet for early detection and referral of individuals with "typical" early symptoms of undiagnosed rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). METHODS: The websites and selected links identified by search terms of typical symptoms were evaluated for health information quality, readability, and whether or not the sites prioritized possibilities and suggested actions. RESULTS: None of the websites examined were completely suitable for finding undiagnosed persons with early RA or SLE. Although the websites had accurate information, their reading levels were too high for the average reader, and were generally poor in terms of giving a differential diagnosis, prioritizing the possibilities and none provided an algorithm for action. CONCLUSIONS: Internet sites could be enhanced for early detection and referral. The internet has become an important factor in clinical practice and physicians are increasingly explaining or responding to the information that their patients find on the internet. Our study shows that the information available to individuals with undiagnosed RA and SLE is likely to be of little help to them and could delay their seeking appropriate attention.