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ID PMID Title PublicationDate abstract
21131273 Angiopoietin-2 is highly correlated with inflammation and disease activity in recent-onset 2011 Apr OBJECTIVE: To investigate whether serum levels of endothelial cell activation markers in early RA patients can serve as biomarkers for inflammation and disease activity, and are associated with radiological progression and development of cardiovascular disease (CVD). METHODS: Serum levels of VEGF, soluble vascular cell adhesion molecule (sVCAM)-1 and angiopoietin-2 (Angpt-2) were measured by ELISA in 176 patients with recent-onset RA, at the time of diagnosis and after 2 years. Markers of inflammation and disease activity were assessed, as well as radiological damage of hands and feet, at diagnosis and after 2 years. Prevalence of CVD of all patients after 12.5 years disease duration was retrieved from medical records. RESULTS: Patients with RA had higher levels of VEGF and Angpt-2 at disease onset compared with healthy controls, which correlated with markers of inflammation, but were not predictive of radiological progression after 2 years. Angpt-2 levels, moreover, significantly correlated with measures of disease activity. Nearly 18% of RA patients developed CVD after an average of 12.5 years of disease, and these patients had a significantly higher level of Angpt-2 at the onset of RA compared with patients who did not develop CVD. CONCLUSIONS: In early RA, markers of endothelial activation are highly correlated with inflammation and disease activity, but not with radiological progression. Angpt-2 could be predictive for the development of CVD since Angpt-2 levels were significantly higher in CVD patients than in non-CVD patients.
20149317 Rheumatoid cachexia and cardiovascular disease. 2009 Nov OBJECTIVE: It has been frequently stated that rheumatoid cachexia (RC) associates with increased cardiovascular risk; however, no studies to date have investigated this. The aim of this study was to investigate the association of RC with multiple novel and classical cardiovascular disease (CVD) risk factors and the presence of established CVD in rheumatoid arthritis (RA). METHODS: A total of 34 RA patients with RC (RA+RC) were identified from a database of 400 RA patients using published RC criteria and compared to the remaining patients (RA-RC) who did not fulfil RC criteria. All patients were assessed for fat and fat-free mass, albumin (indicator of catabolism), disease activity/severity, novel and classical risk CVD factors and established CVD. RESULTS: Fat-free mass (kg) and albumin (g/L) were significantly decreased in RA+RC vs. RA-RC patients: 37.3(33.9-41.6) vs. 45.9(41.2-55.5), p<0.001 and 39.6 + or - 6.7 vs. 42.4 + or - 4.9, p=0.001). Percent body fat was not significantly different. No significant differences were detected in either the classical or novel CVD risk factors, 10-year CVD risk or the prevalence of established CVD. CONCLUSIONS: RC does not appear to be associated with worse CVD profile in RA patients, but this needs to be confirmed in prospective studies.
20496068 Dietary alpha lipoic acid supplementation prevents synovial inflammation and bone destruct 2011 Dec Rheumatoid arthritis (RA) is a chronic inflammatory disorder characterized by chronic inflammation and joint destruction. In this study, we investigated whether dietary supplementation with alpha lipoic acid (ALA) suppresses collagen-induced arthritis (CIA) in mice. Mice were randomly divided into three groups: (1) a control CIA group was fed a normal diet, (2) a CIA group was fed a 0.1% ALA diet (average ALA intake of 160 mg/kg/day), and (3) a CIA group was fed a 0.5% ALA diet (average ALA intake of 800 mg/kg/day). The ALA-fed mice showed a decreased incidence and severity of arthritis compared to the normal diet group. Radiographic findings revealed a dramatic decrease in bone destruction, and histological findings showed extensively suppressed pathological changes in the ALA-fed mice. The ALA-fed mice exhibited inhibited generation of tartrate resistant acid phosphatase (TRAP)-positive osteoclasts in vivo. Additionally, ALA-fed mice reduced production of various proinflammatory cytokines and the soluble receptor activator of NF-κB ligand (sRANKL) in the joint tissues and the sera. In conclusion, dietary supplementation with ALA attenuated inflammatory responses and bone destruction in CIA mice.
19404997 Predicting depression in rheumatoid arthritis: the signal importance of pain extent and fa 2009 May 15 OBJECTIVE: To determine the incidence of self-reported depression (SRD) in rheumatoid arthritis and to identify and rank clinically useful predictors of depression. METHODS: We assessed 22,131 patients for SRD between 1999 and 2008. We collected demographic, clinical and treatment data, household income, employment and work disability status, comorbidity, scales for function, pain, global, and fatigue, the Regional Pain Scale (RPS), the Symptom Intensity (SI) scale (a linear combination of the RPS and the fatigue scales) and linear combinations of the Health Assessment Questionnaire, pain and global severity. We used logistic regression analyses with multivariable fractional polynomial predictors, and Random Forest analysis to determine the importance of the predictors. RESULTS: The cross-sectional prevalence of self-reported depression was 15.2% (95% confidence interval [95% CI] 14.7-15.7%) and the incidence rate was 5.5 (95% CI 5.3-5.7) per 100 patient years of observation. The cumulative risk of SRD after 9 years was 38.3% (95% CI 36.6-40.1%). Almost all variables were significant predictors in logistic models. In Random Forest analyses, the SI scale, followed by comorbidity, best predicted self-reported depression, and no other variable or combination of variables improved prediction compared with the SI scale. CONCLUSION: Pain extent and fatigue (SI scale) are the dominant predictors of SRD. These variables, also of central importance in the symptomatology of fibromyalgia, are powerful markers of distress. A strong case can be made for the inclusion of these assessments in routine rheumatology practice. In addition, actual knowledge of comorbidity provides important insights into the patient's global health and associated perceptions.
19834653 Whole-body FDG-PET/CT on rheumatoid arthritis of large joints. 2009 Nov OBJECTIVE: Fluorodeoxyglucose (FDG) uptake in joint lesions in patients with rheumatoid arthritis (RA) reportedly represents the degree of synovial inflammation. Most previous studies have focused on small joints, and the application of whole-body positron emission tomography (PET) combined with computed tomography (CT) (PET/CT) for the evaluation of inflammatory activity in large joints has not been well studied. METHODS: Eighteen patients with RA underwent FDG-PET/CT. FDG uptake in the knee, hip, carpal, wrist, elbow, shoulder, and atlanto-axial joint (total of 13 joints) and in the axillary lymph nodes was evaluated by calculating the maximum standardized uptake value (SUV(max)) and the visual uptake scores as follows: 0, no uptake; 1, slight uptake; 2, moderate uptake (same as in liver); 3, higher than in liver; 4, highest uptake. The number of painful/swollen joints, the white blood cell (WBC) count, and the C-reactive protein (CRP) level were also evaluated. RESULTS: Whole-body FDG-PET/CT delineated large-joint lesions in patients with RA, and the metabolic activity of inflammation was accurately overlaid on the joint anatomy. The total FDG score for all 13 joints was significantly correlated with the CRP level (r = 0.653, p < 0.01, n = 18). The total SUV(max) and the CRP level were weakly, but not significantly, correlated (r = 0.377, p > 0.05). The WBC count was not correlated with any other parameter. The mean number of joints per patient with an FDG uptake score of 2 or more was significantly larger than the mean number of painful/swollen joints (6.2 +/- 3.3 vs. 3.1 +/- 2.7, n = 18, p < 0.01) and both parameters were strongly correlated (r = 0.588, p < 0.01, n = 18). Also, FDG uptake score and SUV of painful/swollen joints were significantly higher than these of not painful/swollen joints. FDG uptake was significantly different from patients of remission and patients of active arthritis. Uptake in the atlanto-axial joint was observed in five (mostly asymptomatic) patients (5/18, 28%), and the uptake score was significantly correlated with the total FDG score (r = 0.669, p < 0.01, n = 18). The axillary lymph nodes score was correlated with the arm joints score. CONCLUSION: FDG-PET/CT represents the inflammatory activity in large joints in patients with RA accurately and sensitively and may be helpful for early evaluations of the extent of RA throughout the whole body including high risk lesion of atlanto-axial joint. Furthermore, the visual FDG uptake score may be useful for evaluating arthritis in large joints.
19370184 Blocking TNF in vitro with infliximab determines the inhibition of expansion and interfero 2009 Jan BACKGROUND: Side effects of TNF neutralisation - mostly infectious complications - were recognized, the most important being pulmonary tuberculosis infections. gamma/ d T cells contribute to protective immune response against mycobacterium tuberculosis. OBJECTIVES: The aim of the present study was to assess the expansion capacity of Vgamma9/Vdelta2 T cells from (tuberculin purified protein derivative (PPD) positive and PPD negative) patients with active rheumatoid arthritis (RA), and to examine the in vitro effect of infliximab on this lymphocyte subset. METHODS: 28 PPD negative RA patients were studied and compared with 14 PPD positive RA patients, 45 PPD-negative and 110 PPD-positive healthy volunteers. Cell separation, expansion in vitro of Vgamma9/Vdelta2 T lymphocytes (EF) and the expression of tumor necrosis factor receptor II and IFN-gamma content by Vgamma9/Vdelta2 T lymphocytes were studied before and after infliximab in vitro addiction. RESULTS: The EF from PPD positive subjects was higher than that from PPD negatives. Patients with RA have the highest levels. The addition of infliximab to the cultures from PPD-positive patients determined a significant inhibition of cell expansion and TNF RII expression and a significant decrease of IFN gamma content. CONCLUSION: In this study we have documented that gamma/ delta T lymphocytes from patients with PPD positive rheumatoid arthritis have a high capacity to respond in vitro to phosphoantingens with expansion TNF-RII expression and IFN gamma production that is inhibited by the exposure to infliximab. These results might be of relevance in view of the effect of TNF blocking on the pulmonary tuberculosis infection.
19324521 Genetics of rheumatoid arthritis: underlying evidence of ethnic differences. 2009 May A new age has begun in the genetics of rheumatoid arthritis (RA), as genome-wide association studies scanning the human genome have been put into practical use. Among the RA-susceptibility genes identified by genetic studies, HLA-DRB1 gene appears to represent the most major determinant of genetic predisposition to RA. However, inconsistent results of the contributions of non-HLA susceptibility genes have been described, with the exception of a few genes repeatedly associated with RA-susceptibility, such as PTPN22 gene in populations of European ancestry and PADI4 gene in populations of Asian ancestry, revealing the presence of genetic heterogeneity in RA. We review herein recent advances in the genetics of RA and discuss the underlying differences among populations of European and Asian ancestries, taking as examples our previous findings for RA-susceptibility genes in the Japanese population: PADI4; FCRL3; and CD244.
19037609 Infiltrations of plasma cells in synovium are highly associated with synovial fluid levels 2009 May Infiltration of plasma cells can be a histopathological hallmark of articular synovium with rheumatoid arthritis (RA). A proliferation-inducing ligand (APRIL) may have key roles in homeostasis and development of B cells, and the differentiation of B cells into plasma cells. This study was designed to explore the relationships between the infiltrations of plasma cells in synovium and the synovial fluid levels of APRIL in inflamed peripheral joints of RA. Synovium and synovial fluid were sampled from 21 RA patients underwent arthroscopic synovectomy for inflamed peripheral joints. The variants of rheumatoid synovium were classified into the follicular and diffuse synovitis by hematoxylin and eosin staining, and the infiltrations of plasma cells in rheumatoid synovium were quantified under the light microscope. The synovial fluid levels of APRIL were measured with the enzyme-linked immunosorbent assay. The mean number of infiltrating plasma cells in synovium and the mean synovial fluid level of APRIL were significantly increased in follicular synovitis compared with those in diffuse synovitis (P = 0.009, and P = 0.018, respectively), and there was a highly positive association between the infiltrations of plasma cells and the synovial fluid levels of APRIL among all of the RA patients (Rs = 0.776, P < 0.001). These findings suggest that the local production of APRIL may be associated with the ectopic lymphoid neogenesis in rheumatoid synovium and may have a role in contributing to the infiltration of plasma cells in synovium within inflamed peripheral joints of RA.
20091587 Surgical interventions for the rheumatoid shoulder. 2010 Jan 20 BACKGROUND: Involvment of the shoulder joint in patients with rheumatoid arthritis (RA) leads to severe destruction of the glenohumeral joint. When conservative treatment does not result in sufficient improvement, surgical procedures may be considered as the only beneficial treatment option. OBJECTIVES: To assess beneficial and harmful effects of all forms of surgical treatment in the management of the shoulder in people with rheumatoid arthritis. SEARCH STRATEGY: Articles were identified by searches in The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, SCISEARCH and reference lists of relevant articles (January 1995 to May 2008). SELECTION CRITERIA: Randomised Controlled Trials, and Controlled Clinical Trials reporting on effects of shoulder surgery. In addition case-series were included for the assessment of complications. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion, assessed trial quality and extracted the data. MAIN RESULTS: One RCT, one CCT and 21 case-series were included. The RCT compared cemented versus uncemented humeral stem fixation in arthroplasty and found no significant differences between the two groups after two years (low quality evidence). The CCT compared rotator cuff repair with augmented subscapularis transposition versus subscapularis transposition alone and reported significant differences in favour of the augmented subscapularis transposition after 2 years in function, mean difference (MD) 4.00 on a 0 to 30 scale (95% CI 1.11 to 6.89) and pain, MD 4.00 on a 0 to 20 scale (95% CI 0.84 to 7.16) (low quality evidence). Based on 11 case series (mean follow up 4.5 to 12 years) complications were reported in 11% (95% CI: 9.9% to 12.1%) of the total shoulder arthroplasties, while 10 case-series (mean follow-up 2.7 to 11.3 years) reported complications in 9.9% (95% CI: 8.4% to 11.4%) of the hemiarthroplasties (very low quality evidence). AUTHORS' CONCLUSIONS: The effects of surgical treatment in the management of the shoulder in people with rheumatoid arthritis are largely unknown due to the paucity of randomised controlled trials.
18987777 Pregnancy and rheumatic disease: "by the book" or "by the doc". 2009 Jan Pregnancy is an important condition that can affect and be affected by rheumatic disease. Overall, pregnancy is viewed as a Th2-predominant state, but several Th1-related cytokines are vital to early pregnancy. In rheumatoid arthritis for example, the majority of women improve by the beginning of the second trimester, but the majority (90%) will flare in the first 3 to 4 months postpartum. In contrast, systemic lupus erythematosus has an unpredictable course in pregnancy, leaving most rheumatologists to recommend a disease-quiescent state prior to conception. Other diseases such as scleroderma are less clear because the disease less commonly presents in the childbearing period. Many immunosuppressive medications for the rheumatic diseases are contraindicated in pregnancy because of their mechanisms of action leaving only a select few "safe" medications. Significant heterogeneity between the Food and Drug Administration (FDA) category for a medication and what a rheumatologist does in clinic leads to confusion on how a patient should be treated for active rheumatic disease both peripartum and postpartum, particularly if the patient is breastfeeding. We review the general state of pregnancy and how it is affected by prototypical rheumatic diseases including rheumatoid arthritis and systemic lupus erythematosus. In addition, we present the most commonly used disease-modifying antirheumatic drugs and immunosuppressants and explain the difference between the FDA category and clinical practice among rheumatologists. Finally, we provide some general recommendations on how to manage a rheumatic disease during pregnancy including: (a) preconception planning to ensure no teratogenic medications on board, (b) early disclosure of pregnancy to all caregivers including the rheumatologist, family physician, obstetrician, and maternal-fetal medicine specialist, and (c) planning of safe medication use for acute flare-ups and disease suppression peripartum and postpartum.
19116934 The chromosome 7q region association with rheumatoid arthritis in females in a British pop 2009 Jan OBJECTIVE: The single-nucleotide polymorphism (SNP) rs11761231 on chromosome 7q has been reported to be sexually dimorphic marker for rheumatoid arthritis (RA) susceptibility in a British population. We sought to replicate this finding and to better characterize susceptibility alleles in the region in a North American population. METHODS: DNA from 2 North American collections of RA patients and controls (1,605 cases and 2,640 controls) was genotyped for rs11761231 and 16 additional chromosome 7q tag SNPs using Sequenom iPlex assays. Association tests were performed for each collection and also separately, contrasting male cases with male controls and female cases with female controls. Principal components analysis (EigenStrat) was used to determine association with RA before and after adjusting for population stratification in the subset of the samples for which there were whole-genome SNP data (772 cases and 1,213 controls). RESULTS: We failed to replicate an association of the 7q region with RA. Initially, rs11761231 showed evidence for association with RA in the North American Rheumatoid Arthritis Consortium (NARAC) collection (P=0.0073), and rs11765576 showed association with RA in both the NARAC (P=0.038) and RA replication (P = 0.0013) collections. These markers also exhibited sex differentiation. However, in the whole-genome subset, neither SNP showed significant association with RA after correction for population stratification. CONCLUSION: While 2 SNPs on chromosome 7q appeared to be associated with RA in a North American cohort, the significance of this finding did not withstand correction for population substructure. Our results emphasize the need to carefully account for population structure to avoid false-positive disease associations.
20737187 The short-term outcome of the modified Sauvé-Kapandji procedure regarding range of motion 2011 Feb The Sauvé-Kapandji (S-K) procedure is a common treatment for rheumatoid wrists, but in some cases severe bone destruction makes this operative modality difficult to perform, while also resulting in a poor outcome. A modified S-K procedure for these wrists has been reported, but the clinical outcomes of the modified procedure are unclear. This study evaluated 24 wrists in 20 patients who underwent the modified S-K procedure. The mean follow-up period was 34.5 months. The clinical assessments were range of motion, carpal bone translation and bony shelf size. The range of motion and carpal bone translation were similar to those produced by the S-K procedure. In regard to bony shelf size, wrists with an excessively large bony shelf tended to have a progression of carpal bone translation toward the palmar direction due to the residual malposition of the ECU tendon. The modified S-K procedure appears to be a safe and effective surgical alternative for the treatment of severely destroyed rheumatoid wrists. Although the modified procedure allows for the adjustment of the bony shelf size, it should not be used with wrists that have an excessively large bony shelf.
21082209 Serodiagnosis of Mycobacterium avium-complex pulmonary disease with an enzyme immunoassay 2011 Apr Rheumatoid arthritis (RA) has many pulmonary manifestations, including bronchial abnormalities that can develop into Mycobacterium avium-complex (MAC) pulmonary disease (PD). MAC-PD can be lethal in patients receiving tumor necrosis factor-alpha blockers despite administration of antibiotics. Diagnosis of MAC-PD is often difficult, because MAC is an environmental organism. In this study, we investigated the usefulness of serodiagnosis of MAC-PD in RA patients by using an enzyme immunoassay (EIA) kit that detects anti-glycopeptidolipid (GPL) core antigen IgA antibodies. Antibody levels were measured in 63 patients with RA: 14 with MAC-PD plus 3 cultured nontuberculous mycobacteria (NTM) other than MAC, 16 with pulmonary abnormalities characterizing NTM but undetected in sputum culture, and 30 control subjects. RA patients with MAC-PD showed significantly higher antibody levels than controls (p = 0.02). The cutoff point was set at 0.7 IU/l, making the sensitivity and specificity of the antibody in MAC-PD and control patients 43% and 100%, respectively. The EIA kit is useful for diagnosis of MAC-PD in RA patients because of its high specificity. This test is an easier and less invasive form of examination and could therefore replace bronchoscopy as the main diagnostic procedure for RA patients with MAC-PD.
19168802 Influence of controlled rheumatoid arthritis on the action and disposition of verapamil: f 2009 Mar Active rheumatoid arthritis (RA), obesity, and old age are associated with reduced responsiveness to the calcium channel antagonist verapamil despite increased drug concentrations. The diminishing effect appears to be associated with the severity of inflammation. We examined pharmacodynamics and pharmacokinetics of verapamil in patients with controlled RA. Volunteers included RA patients in remission: 12 on infliximab, 8 on other antirheumatic therapy, and 12 healthy subjects. Verapamil plasma concentrations and selected inflammatory mediators as well as blood pressure and electrocardiographic parameters were recorded after a single 80-mg dose of verapamil. Inflammatory mediators were all below what is reported for active RA, confirming that RA was controlled. The tumor necrosis factor-alpha concentration, however, was significantly higher in the infliximab group compared with other groups and the literature value for active RA. No significant difference was observed between groups in terms of percentage prolongation of PR interval despite a trend toward a lower response in the RA groups, the mean plasma concentrations, and the total and unbound area under the curve of verapamil. However, the slope of the S-verapamil concentration-effect curve was steeper for controls compared with the RA patients. Remission from active disease appears to restore plasma protein levels and hepatic drug metabolism activity in patients with RA, resulting in relatively normal verapamil pharmacokinetics.
19517156 Does TNF-alpha blockade play any role in cardiovascular risk among rheumatoid arthritis (R 2009 Oct The aims of this study were to determine the association and potential mechanisms between TNF-antagonists and increased cardiovascular risk in rheumatoid arthritis (RA) patients. Three groups of RA patients were studied; ten treated with TNF-antagonists, 13 with methotrexate, and 14 were naïve to treatment. Mean age: 47.2 (SD 11.3), 52.3 (SD 16.6), and 51.2 (SD 13.3) years; mean disease duration 102 (SD 90.4), 72.9 (SD 67.3), and 71.3 (SD 87.1) months, and treatment duration 24.2 (SD 18.5), 34.7 (SD 32.2), and 0 months for each group. CLINICAL DATA: systolic and diastolic blood pressure and body mass index were assessed. Disease activity was determined by DAS-28 index. An ELISA assay for IL-6, sIL-6 R, IFN-gamma, TNF-alpha, sTNFRI, sTNFRII, IGF I, and adiponectin were performed. Fasting glucose, insulin, lipid profile, CRP, and ESR were also done. HOMA-IR and QUICKI indexes were calculated. Statistically significant differences observed between the TNF group and the other two groups were: TNF-alpha levels (p, 0.0014), soluble TNF RII (p, 0.0432), IFN-gamma (p, 0.008), and DAS-28 <2.6 (p, 0.033). Finding of elevated levels of sTNFRII and IFN-gamma in patients with RA on anti-TNF suggests that this therapy does not completely suppress the inflammatory process and may promote atherogenesis.
19678907 New data favouring that neurotrophins are of importance in arthritis. 2009 Neurotrophins are important in inflammation. In an article in Arthritis Research & Therapy, Barthel and collaborators give new information on the existence of neurotrophin production in the synovial tissue of arthritic joints. These findings, together with other recent findings, stress that neurotrophins should be considered important factors in arthritis. This is reinforced by the facts that they are also produced by articular chondrocytes and that receptors for these are present in the synovial tissue and on chondrocytes. The importance of neurotrophins in joints should be further studied, including examinations on the efficacy of interfering with their effects in arthritis.
20098085 Composite cutaneous lymphoma in a patient with rheumatoid arthritis treated with methotrex 2010 Feb Patients with rheumatoid arthritis, whether treated or not with immunosuppressive agents including methotrexate, have an increased risk of lymphoproliferative disorders. Termed "iatrogenic immunodeficiency-associated lymphoproliferative disorders" in the 2008 World Health Organization classification of lymphoid neoplasms, they include Hodgkin and non-Hodgkin lymphomas. Composite lymphomas are rare, particularly in skin, with none reported in immunodeficiency states. We report the case of a 67 year-old woman with a long history of rheumatoid arthritis, on methotrexate treatment, who developed multiple skin lesions exhibiting a malignant infiltrate displaying both B- and T-cell phenotypes and dual clonal gene rearrangement by polymerase chain reaction, consistent with a cutaneous composite lymphoma. The patient received chemotherapy including rituximab with partial response, but the T-cell component recurred. To the best of our knowledge, this is the first case report of a cutaneous composite lymphoma in a patient with an iatrogenic immunodeficiency representing a dual challenge, diagnostic for the pathologist and therapeutic for the hematologist.
19116908 Stimulation of nicotinic acetylcholine receptors attenuates collagen-induced arthritis in 2009 Jan OBJECTIVE: The parasympathetic nervous system, through the vagus nerve, can down-regulate inflammation in vivo by decreasing the release of cytokines, including tumor necrosis factor alpha (TNFalpha), by activated macrophages. The vagus nerve may exert antiinflammatory actions via a specific effect of its principal neurotransmitter, acetylcholine, on the alpha7 subunit of nicotinic acetylcholine receptors (alpha7nAChR) on macrophages. The present study was undertaken to obtain insight into the role of the cholinergic antiinflammatory pathway in arthritis. METHODS: To inhibit the cholinergic antiinflammatory pathway, mice were subjected to unilateral cervical vagotomy or sham surgery, after which arthritis was induced with type II collagen. In a separate study, nicotine was added to the drinking water of mice with collagen-induced arthritis (CIA). In addition, we investigated the effects of intraperitoneally (IP)-injected nicotine and the specific alpha7nAChR agonist AR-R17779. RESULTS: Clinical arthritis was exacerbated by vagotomy and ameliorated by oral nicotine administration. Moreover, oral nicotine inhibited bone degradation and reduced TNFalpha expression in synovial tissue. Both IP-injected nicotine and AR-R17779 ameliorated clinical arthritis and reduced synovial inflammation. This was accompanied by a reduction of TNFalpha levels in both plasma and synovial tissue. The effect of AR-R17779 was more potent compared with that of nicotine and was associated with delayed onset of the disease as well as with protection against joint destruction. CONCLUSION: These data provide the first evidence of a role of the cholinergic antiinflammatory pathway in the murine CIA model of rheumatoid arthritis.
19134200 No evidence of major effects in several Toll-like receptor gene polymorphisms in rheumatoi 2009 INTRODUCTION: The objective was to study the potential genetic contribution of Toll-like receptor (TLR) genes in rheumatoid arthritis (RA). TLRs bind to pathogen-associated molecular patterns, and TLR genes influence both proinflammatory cytokine production and autoimmune responses. Host-pathogen interactions are involved in RA physiopathology. METHODS: We tested SNPs of five TLR genes (TLR9, TLR2, TLR6, TLR1, and TLR4) in a cohort of 100 French families with RA. Genotypes were analyzed using the transmission disequilibrium test. As TLR2, TLR6, and TLR1 are located on chromosome 4, we determined the haplotype relative risk. Analyses were performed in subgroups defined by status for rheumatoid factor, anti-cyclic citrullinated peptide autoantibodies, and erosions. RESULTS: We found no disequilibrium in allele transmission for any of the SNPs of the five TLR genes. In subgroup analyses, no associations were detected linking TLR9, TLR2, or TLR9/TLR2 to rheumatoid factor, anti-cyclic citrullinated peptide autoantibodies, or erosions. Haplotype analysis of the polymorphisms showed no haplotype associations in any of the subgroups. CONCLUSIONS: We found no evidence of major effects of TLR gene polymorphisms in RA, although we tested different TLR phenotypes. Moreover, no associations were noted with autoantibody production or erosions.
20055986 Forefoot disease activity in rheumatoid arthritis patients in remission: results of a coho 2010 INTRODUCTION: The aim of our study was to investigate the presence of disease activity in the metatarsophalangeal (MTP) joints of the forefoot in rheumatoid arthritis (RA) patients in remission according to the Disease Activity Score based on 28 joints (DAS28) remission criterion. METHODS: A total of 848 patients with recent-onset RA were included from 1995 through 2007. The DAS28 and pain and swelling of the MTP joints were assessed annually. The data were analyzed using descriptive techniques. RESULTS: On average, 35% of the patients fulfilled the remission criterion of DAS28 <2.6 during the first eight years of RA. On average, 29% of these patients had at least one painful MTP joint and, on average, 31% had at least one swollen MTP joint during follow-up. Forty percent, on average, had at least one involved MTP joint (pain and/or swelling). CONCLUSIONS: Painful and/or swollen MTP joints were detected in a substantial proportion of patients classified as being in remission. Therefore, examination of the foot joints - irrespective of the patient's state of remission - seems indicated in order to provide optimal foot care.