Browse

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

ID PMID Title PublicationDate abstract
22460146 Defining remission in rheumatoid arthritis. 2012 Apr OBJECTIVE: Given the inconsistency of remission definitions in rheumatoid arthritis (RA) trials, the goal of this American College of Rheumatology/European League Against Rheumatism committee was to define remission. METHODS: The committee instructed a working group that a new remission definition, among other requirements, needed to allow for little, if any, active clinical disease and to be defined using the core set of outcome measures for RA trials and that those in remission at one time needed to have a low risk of later worsening function or radiograph progression. Remission was to be defined using trial data for use in trials but needed to anticipate use in a practice setting. RESULTS: The working group started by evaluating the thresholds for core set measures compatible with remission and determined that patient-reported outcomes contributed importantly to the ability of outcome assessment to distinguish more from less effective treatments. The group created a candidate group of remission definitions to test, including Boolean versions and widely used indexes. Testing how well these candidate definitions predicted later good outcomes, the group found that Disease Activity Score 28 thresholds for remission performed worse than Simplified Disease Activity Index/Clinical Disease Activity Index or Boolean versions. Also, persons with low Disease Activity Score 28 occasionally had high joint counts, which were incompatible with remission. The parent committee chose two definitions: one Boolean (patient had to have all of the following: tender joint count, swollen joint count ≤ 1, C reactive protein ≤ 1 mg/dl) and patient global assessment ≤ 1 (on a 0-10 scale) and one Simplified Disease Activity Index ≤ 3.3. CONCLUSION: The American College of Rheumatology/European League Against Rheumatism has promulgated two new similar definitions of remission for RA trials.
22855296 Managing macrophages in rheumatoid arthritis by reform or removal. 2012 Oct Macrophages play a central role in the pathogenesis of rheumatoid arthritis (RA). There is an imbalance of inflammatory and antiinflammatory macrophages in RA synovium. Although the polarization and heterogeneity of macrophages in RA have not been fully uncovered, the identity of macrophages in RA can potentially be defined by their products, including the co-stimulatory molecules, scavenger receptors, different cytokines/chemokines and receptors, and transcription factors. In the last decade, efforts to understand the polarization, apoptosis regulation, and novel signaling pathways in macrophages, as well as how distinct activated macrophages influence disease progression, have led to strategies that target macrophages with varied specificity and selectivity. Major targets that are related to macrophage development and apoptosis include TNF-α, IL-1, IL-6, GM-CSF, M-CSF, death receptor 5 (DR5), Fas, and others, as listed in Table 1. Combined data from clinical, preclinical, and animal studies of inhibitors of these targets have provided valuable insights into their roles in the disease progression and, subsequently, have led to the evolving therapeutic paradigms in RA. In this review, we propose that reestablishment of macrophage equilibrium by inhibiting the development of, and/or eliminating, the proinflammatory macrophages will be an effective therapeutic approach for RA and other autoimmune diseases.
22355377 Caucasian and Asian specific rheumatoid arthritis risk loci reveal limited replication and 2012 Genome-wide association studies and meta-analysis indicate that several genes/loci are consistently associated with rheumatoid arthritis (RA) in European and Asian populations. To evaluate the transferability status of these findings to an ethnically diverse north Indian population, we performed a replication analysis. We investigated the association of 47 single-nucleotide polymorphisms (SNPs) at 43 of these genes/loci with RA in a north Indian cohort comprising 983 RA cases and 1007 age and gender matched controls. Genotyping was done using Infinium human 660w-quad. Association analysis by chi-square test implemented in plink was carried out in two steps. Firstly, association of the index or surrogate SNP (r2>0.8, calculated from reference GIH Hap-Map population) was tested. In the second step, evidence for allelic/locus heterogeneity at aforementioned genes/loci was assessed for by testing additional flanking SNPs in linkage equilibrium with index/surrogate marker.Of the 44 European specific index SNPs, neither index nor surrogate SNPs were present for nine SNPs in the genotyping array. Of the remaining 35, associations were replicated at seven genes namely PTPN22 (rs1217407, p = 3×10(-3)); IL2-21 (rs13119723, p = 0.008); HLA-DRB1 (rs660895, p = 2.56×10(-5); rs6457617, p = 1.6×10(-09); rs13192471, p = 6.7×10(-16)); TNFA1P3 (rs9321637, p = 0.03); CCL21 (rs13293020, p = 0.01); IL2RA (rs2104286, p = 1.9×10(-4)) and ZEB1 (rs2793108, p = 0.006). Of the three Asian specific loci tested, rs2977227 in PADI4 showed modest association (p<0.02). Further, of the 140 SNPs (in LE with index/surrogate variant) tested, association was observed at 11 additional genes: PTPRC, AFF3, CD28, CTLA4, PXK, ANKRD55, TAGAP, CCR6, BLK, CD40 and IL2RB. This study indicates limited replication of European and Asian index SNPs and apparent allelic heterogeneity in RA etiology among north Indians warranting independent GWAS in this population. However, replicated associations of HLA-DRB1, PTPN22 (which confer ∼50% of the heritable risk to RA) and IL2RA suggest that cross-ethnicity fine mapping of such loci is apposite for identification of causal variants.
22193228 Impact of comorbidities on TNF inhibitor persistence in rheumatoid arthritis patients: an 2012 Dec The aim of this study is to evaluate tumor necrosis factor (TNF) inhibitor persistence and the impact of comorbidity on treatment persistence in patients with rheumatoid arthritis (RA). In a Korean National Health Insurance claims database, patients with a diagnosis code of RA (M05 or M06) who started TNF inhibitor therapy between July 1, 2007 and June 30, 2008 were enrolled. The study cohort was followed until December 31, 2009. Persistence was examined using Kaplan-Meier survival analysis, and multivariate Cox proportional hazard models were developed to examine the potential impact of comorbidities on drug persistence. A total of 388 patients were enrolled in the study cohort. The mean persistence rate in the overall population was 61% at 18 months. Drug survival rates for adalimumab and etanercept at 6 months were 82 and 85%, respectively, and 73 and 78%, respectively, at 12 months. Charlson comorbidity index (CCI) scores and comorbidities such as diabetes, chronic pulmonary disease, mild liver disease, and depression at initiation were not related with drug persistence, while peptic ulcer disease (PUD) lowered the risk of discontinuation of TNF inhibitors (HR 0.73, 95% CI 0.55-0.97). Old age (HR 1.59, 95% CI 1.09-2.33) and prescription of inhibitors by an internist (HR 1.59, 95% CI 1.02-2.48) were associated with discontinuation of TNF inhibitors. The persistence of TNF inhibitors was 61% at 18 months. CCI score and other comorbidities were not related with early discontinuation of TNF inhibitors, while PUD was an independent contributing factor to TNF inhibitor persistence.
21953961 Assessment of intracellular methotrexate and methotrexate-polyglutamate metabolite concent 2011 Oct 30 A new ultrafast quantitative and high-throughput mass spectrometric method using matrix-assisted laser desorption/ionization triple quadrupole tandem mass spectrometry has been developed and validated for determination of intracellular erythrocyte concentrations of the antifolate drug methotrexate (MTX) and its polyglutamate metabolites. The method consists of a solid-phase extraction of MTX and MTX-polyglutamate metabolites from deproteinized erythrocyte lysates spiked with aminopterin as internal standard. The newly developed method was validated according to the most recent FDA guidelines on linearity, recovery, within-run and between-run accuracy and precision and stability of the analytes. The low limit of quantification (LLOQ) was 10 nmol/L for all analytes while the limit of detection (LOD) determined at a signal-to-noise (S/N) ratio = 3:1 in drug- free erythrocyte lysate was on average 0.3 nmol/L. After validation, the new method was used in the measurement of intracellular erythrocyte concentrations of MTX and MTX-polyglutamate metabolites (MTXPG2 to MTXPG7) in packed human erythrocyte samples collected from patients with rheumatoid arthritis receiving low-dose oral methotrexate therapy. Mean (SD) intracellular erythrocyte concentrations observed in patient samples were 12.8 (12.6), 12.4 (9.4), 44.4 (30.0), 33.6 (35.9) and 9.4 (8.2) nmol/L for MTX to MTXPG5, respectively, in 10(6) erythrocytes. The highest observed glutamylation degree of MTX was MTXPG5, the very long chain MTX-polyglutamate metabolites MTXPG6 and MTXPG7 were not detected in the packed erythrocyte pellets collected from rheumatoid arthritis patients.
21287514 [No association of K469E polymorphism of intercellular adhesion molecule-1 with rheumatoid 2011 Feb OBJECTIVE: To investigate the association of the intercellular adhesion molecule-1 gene (ICAM-1) K469E polymorphism and rheumatoid arthritis (RA). METHODS: Two hundred and seventy-five patients with RA and 254 healthy individuals were collected and enrolled in the study. The K469E polymorphism of ICAM-1 gene was analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: The genotype frequencies of KK, KE and EE of K469E polymorphism were 0.535,0.411 and 0.054 respectively in the RA patients, and 0.512,0.437 and 0.051 respectively in the healthy individuals, and there was no significant difference between the two groups (chi² = 0.371, P = 0.831). The frequencies of the K469 allele were 0.74 and 0.73 in the RA patients and the controls respectively (chi² = 0.127, P = 0.721, OR = 1.051, 95%CI:0.800-1.381). No significant difference was observed in KK + KE genotype frequencies between the two groups (P = 0.863), with an odds ratio of 0.935 (95%CI:0.436-2.005). CONCLUSION: The K469E polymorphism of the ICAM-1 gene was not associated with the susceptibility of rheumatoid arthritis.
22589377 HDL protein composition alters from proatherogenic into less atherogenic and proinflammato 2013 Apr OBJECTIVE: An atherogenic lipid profile is an established risk factor for cardiovascular (CV) diseases. Interestingly, high inflammatory states as present in rheumatoid arthritis (RA) are associated with unfavourable lipid profile. Data about effects of novel immunomodulating agents as rituximab (RTX) on lipid profile are limited. Therefore, changes in lipids in RTX treated RA patients were evaluated. METHODS: In 49 consecutive RTX treated RA patients, serum and EDTA plasma samples were collected at baseline, 1, 3 and 6 months. In these samples, lipid and levels were assessed to determine changes in time. Surface-enhanced laser desorption/ionisation time-of-flight (SELDI-TOF) MS analysis was performed in six good and six non-responding RA patients to study functional high density lipoprotein (HDL) protein composition changes in time. RESULTS: In the total group (n=49), the atherogenic index decreased from 4.3 to 3.9 (∼9%) after 6 months. Testing for effect modification revealed a difference in the effect on lipid levels between responders and non-responders upon RTX (p<0.001). ApoB to ApoA-I ratios decreased significantly (∼9%) in good responding (n=32) patients. SELDI-TOF MS analysis revealed a significant decrease in density of mass charge (m/z) marker 11743, representing a decrease in serum amyloid A, in good responding patients. CONCLUSION: This study indicates beneficial effects on cholesterol profile upon RTX treatment along with improvement of disease activity. Proteomic analysis of the HDL particle reveals composition changes from proatherogenic to a less proatherogenic composition during 6 months RTX treatment. Whether these HDL particle alterations during immunotherapies result in a lower CV event rate remains to be established.
21970822 Post-menopausal women with rheumatoid arthritis who are treated with raloxifene or alendro 2012 Jul BACKGROUND: Serum undercarboxylated osteocalcin (ucOC) is a biochemical bone marker of vitamin K insufficiency. It had been reported that bone resorption inhibitors tend to decrease the serum ucOC level in patients with primary osteoporosis. In rheumatoid arthritis (RA) patients, these results have never been reported. AIM: We investigated risk factors which could change serum ucOC level in post-menopausal women with RA (no.=100). SUBJECTS AND METHODS: Twenty patients received no bone resorption inhibitor (control), 30 received raloxifene (RLX), while 50 received alendronate (ALN). This cross-sectional study was limited to patients with low RA disease activity (Disease Activity Score-28 ≤3.2). We measured serum ucOC, and the data were analyzed by multivariable analysis, including ucOC and the other variables. RESULTS: Scheffe's F test demonstrated a significant difference in serum ucOC levels between controls and the RLX group (p<0.01), and between controls and the ALN group (p<0.01). Serum ucOC levels were low in both treated groups. An adjusted multivariate analysis was performed for the variables: bone resorption inhibitor use, serum alkaline phosphatase, glucocorticoid dose, age, estimated glomerular filtration rate and matrix metalloproteinase 3. As a result, serum ucOC inversely correlated with bone resorption inhibitor use (p<0.01) and oral glucocorticoid dose (p<0.01), which were independent risk factors of lowering ucOC. CONCLUSIONS: Bone resorption inhibitors and glucocorticoids were independent risk factors for lowering serum ucOC levels in post-menopausal RA patients.
22945690 Bone density and microarchitecture: relationship between hand, peripheral, and axial skele 2012 Nov We assessed the relationship of bone density and microarchitecture between hand, peripheral, and axial skeletal sites using high-resolution peripheral quantitative computed tomography (HR-pQCT) and dual-energy X-ray absorptiometry (DXA) in patients with rheumatoid arthritis (RA) and which factors influence these parameters. This was a cross-sectional study of 100 female patients (53.4 ± 9.3 years) with RA. HR-pQCT scans at distal radius and the second metacarpal head were performed to assess cortical and trabecular volumetric bone mineral density (vBMD) and microarchitecture. DXA scans at the hip, lumbar spine, and ultradistal radius were performed to assess areal BMD. There was significant correlation in vBMD and microarchitectural parameters between the second metacarpal head and distal radius (r = 0.201-0.628). Areal BMD at the axial skeleton was moderately associated with vBMD at the peripheral sites (r = 0.354-0.558). Factors related to disease severity/chronicity significantly correlated with vBMD and microarchitecture at the distal radius and the second metacarpal head. Factors related to disease activity were more likely to correlate with vBMD and microarchitecture at the second metacarpal head but not those at the distal radius. HR-pQCT is a promising technique that is capable of providing detailed quantitative assessment of disease-associated periarticular bone loss at both cortical and trabecular bone compartments in patients with RA. Future longitudinal studies will be needed to investigate whether assessment by HR-pQCT can be used as a marker of disease activity and a predictor of disease progression in RA.
22607783 Mitral valve repair is durable in patients with rheumatoid arthritis. 2012 Aug BACKGROUND: Rheumatoid arthritis (RA) and its treatments are associated with tissue abnormalities, which may influence surgical outcomes of repair for severe mitral valve regurgitation (MR). We examined late survival and durability of mitral valve repair in patients with RA. METHODS: Thirty-six patients with RA (21 male) underwent mitral valve repair for MR from August 1978 to August 2005. Median age was 70 years (range, 22 to 84). Preoperatively, 27 patients (75%) had New York Heart Association Functional Class III/IV symptoms, and 29 (78%) required immunomodulating medications for RA management. Mechanisms of MR were leaflet prolapse in 26 patients (72%), leaflet malcoaptation in 5 (14%), tethering in 4 (11%), and unknown in 1 (3%). RESULTS: All patients underwent mitral valve repair, which included posterior leaflet triangular resection in 11 patients, leaflet plication in 10, and artificial chordae placement in 3. When compared with matched control patients without RA who underwent mitral valve repair, RA patients had decreased survival (27% versus 64%, p=0.005) and freedom from reoperation (93% versus 98%, p=0.04) at 8 years. However, RA patients undergoing mitral valve repair had similar survival at 5 years compared with age- and sex-matched comparator patients with RA who did not undergo mitral valve surgery (65% versus 67%, p=nonsignificant). CONCLUSIONS: Mitral leaflet pathology in RA patients with severe MR is similar to that of non-RA patients with mitral valve disease. Long-term survival after mitral valve repair in RA patients is equivalent to that of the general RA population without mitral valve disease, and the durability of mitral valve repair in these patients is very good.
22137922 The use of conventional disease-modifying anti-rheumatic drugs in established RA. 2011 Aug Conventional disease-modifying anti-rheumatic drugs (DMARDs) are the main tool to treat any form of rheumatoid arthritis (RA). Over the years, treatment strategies and use of DMARDs have changed. 'Tight control' and 'treat-to-target' are now the present paradigms. Combining DMARDs and adapting their dosages to obtain the best (clinical) result in individual RA patients with the least amount of medication has been and is studied worldwide. Literature results are mainly on early RA however, and they do not necessarily also apply to patients with established RA. Methotrexate (MTX) is the key conventional DMARD also for the treatment of established RA, and MTX often has to be combined with other DMARDs to reach low disease activity. However, there is lack of data on combination DMARD strategies and on how to treat best individual patients with established RA. In this review, we address these uncertainties and give an overview of available data.
22394634 [Pharmacological mechanisms of ethyl acetate extraction of Tongbiheji for active T cell si 2012 Mar AIM: To confirm extracts of activity from Traditional Chinese Medicine TongBiHeJi, study effect on two signaling pathways of T cells and clarify the pharmacological mechanisms of TongBiHeJi. METHODS: Concanavalin(ConA) were added successively into rats lymphocytic culture with different extracts of activity from Traditional Chinese Medicine. After 24 hours, CD71 expression rate on rat T lymphocytes activated with ConA was analyzed by flow cytometry. TCR, CD28 and ICOS on T cells were detected after T lymphocytes of rat activated by ConA were cultivated with various EthylAcetate extraction of TongBiHeJi(TBHJ) and Methotrexate (MTX) for 48 hours. RESULTS: CD71 expression rate on rat T lymphocytes induced by ConA was increased to 69.7%. TBHJ inhibited the rate of CD3(+);CD71(+); expression(32.5%); ConA up-regulated TCR, CD28 and ICOS expression on T cells obviously. There was different between ConA and positive control significantly(P<0.001). TBHJ could down-regulate obviously TCR, CD28 and ICOS expression on ConA-activated T lymphocytes with Concentration-dependent, especially ICOS. MTX inhibited CD3(+);CD71(+); and CD3(+);TCR(+); expression also. CONCLUSION: TBHJ inhibited T cells activation by adjusting two signaling pathways. That implied TBHJ could block CD28-ICOS signaling molecules to induce immunological tolerance. This study provided an experimental basis for application of TongBiHeJi to treatment of rheumatoid arthritis.
20868758 Comparison of the NIDS® rapid assay with ELISA methods in immunogenicity testing of two b 2011 Mar INTRODUCTION: Rapid lateral flow immunogenicity assays for the detection of anti-drug antibodies (ADAs) to two biotherapeutic antibodies, an anti-HER2 antibody and an anti-TNF-α antibody, were developed using ANP Technologies, Inc.'s proprietary Nano-Intelligent Detection System (NIDS®) and compared to their ELISA counterparts. METHODS: Biotin and hapten-labeled drugs are incubated with the patient serum sample to allow ADA to form a bridge complex with each drug conjugate. The reaction mixture is then added to a test strip with an anti-hapten capture zone which captures the mixed bridge complex. The bridge-complexed biotinylated drug then reacts with streptavidin-labeled gold particles in situ. The signal developed at the capture zone, which is directly proportional to ADA in the sample, is then quantitatively measured with a handheld reader. The counterpart ELISAs were run using the same reagents. Dose-response, specificity/free drug depletion, and screening cut-point assays were performed using both methods. RESULTS: The rapid assays' performance compare very closely to their ELISA counterparts'. Both types of assays identified the same positive samples in screening a limited population of 50 normal serum samples for the anti-HER2 antibody. In the case of anti-TNF-α, both assays identified the same positive samples out of 50 normal and 20 rheumatoid arthritis patient serum samples but differed in the assessment of two others. The rapid assay correctly identified as negative an ELISA false positive sample, and correctly tested as positive an ELISA false negative sample. Positive results were verified with a specificity/free drug depletion assay. DISCUSSION: The NIDS® rapid immunogenicity assay offers distinct advantages over current methods in simplicity, low cost, and short time to result. More importantly, the method requires no sample dilution and no washing steps which can perturb fragile complexes formed by low-affinity ADAs. Thus, the assay can potentially detect ADAs with various affinities.
21905009 Structural changes of the brain in rheumatoid arthritis. 2012 Feb OBJECTIVE: To investigate whether structural changes are present in the cortical and subcortical gray matter of the brains of patients with rheumatoid arthritis (RA). METHODS: We used two surface-based style morphometry analysis programs and a voxel-based style analysis program to compare high-resolution structural magnetic resonance imaging data obtained for 31 RA patients and 25 age- and sex-matched healthy control subjects. RESULTS: We observed an increase in gray matter content in the basal ganglia of RA patients, mainly in the nucleus accumbens and caudate nucleus. There were no differences in the cortical gray matter. Moreover, patients had a smaller intracranial volume. CONCLUSION: Our results suggest that RA is associated with changes in the subcortical gray matter rather than with cortical gray matter atrophy. Since the basal ganglia play an important role in motor control as well as in pain processing and in modulating behavior in response to aversive stimuli, we suggest that these changes may result from altered motor control or prolonged pain processing. The differences in brain volume may reflect either generalized atrophy or differences in brain development.
22143913 MRI identifies plantar plate pathology in the forefoot of patients with rheumatoid arthrit 2012 Apr Previous cadaveric studies have suggested that forefoot deformities at the metatarsophalangeal (MTP) joints in patients with rheumatoid arthritis (RA) might result from the failure of the ligamentous system and displacement of the plantar plates. This study aimed to examine the relationship between plantar plate pathology and the rheumatoid arthritis magnetic resonance imaging score (RAMRIS) of the lesser (second to fifth) MTP joints in patients with RA using high-resolution 3 T magnetic resonance imaging (MRI). In 24 patients with RA, the forefoot was imaged using 3 T MRI. Proton density fat-suppressed, T2-weighted fat-suppressed and T1-weighted post gadolinium sequences were acquired through 96 lesser MTP joints. Images were scored for synovitis, bone marrow oedema and bone erosion using the RAMRIS system and the plantar plates were assessed for pathology. Seventeen females and 7 males with a mean age of 55.5 years (range 37-71) and disease duration of 10.6 years (range 0.6-36) took part in the study. Plantar plate pathology was most frequently demonstrated on MRI at the fifth MTP joint. An association was demonstrated between plantar plate pathology and RAMRIS-reported synovitis, bone marrow oedema and bone erosion at the fourth and fifth MTP joints. In patients with RA, 3 T MRI demonstrates that plantar plate pathology at the lesser MTP joints is associated with features of disease severity. Plantar plate pathology is more common at the fourth and fifth MTP joints in subjects with RA in contrast to the predilection for the second MTP reported previously in subjects without RA.
21948985 B cell depletion enhances T regulatory cell activity essential in the suppression of arthr 2011 Nov 1 The efficacy of B cell-depletion therapy in rheumatoid arthritis has driven interest in understanding the mechanism. Because the decrease in autoantibodies in rheumatoid arthritis does not necessarily correlate with clinical outcome, other mechanisms may be operative. We previously reported that in proteoglycan-induced arthritis (PGIA), B cell-depletion inhibits autoreactive T cell responses. Recent studies in B cell-depletion therapy also indicate a role for B cells in suppressing regulatory mechanisms. In this study, we demonstrate that B cells inhibited both the expansion and function of T regulatory (Treg) cells in PGIA. Using an anti-CD20 mAb, we depleted B cells from mice with PGIA and assessed the Treg cell population. Compared to control Ab-treated mice, Treg cell percentages were elevated in B cell-depleted mice, with a higher proportion of CD4(+) T cells expressing Foxp3 and CD25. On a per-cell basis, CD4(+)CD25(+) cells from B cell-depleted mice expressed increased amounts of Foxp3 and were significantly more suppressive than those from control Ab-treated mice. The depletion of Treg cells with an anti-CD25 mAb concurrent with B cell-depletion therapy restored the severity of PGIA to levels equal to untreated mice. Although titers of autoantibodies did not recover to untreated levels, CD4(+) T cell recall responses to the immunizing Ag returned as measured by T cell proliferation and cytokine production. Thus, B cells have the capacity to regulate inflammatory responses by enhancing effector T cells along with suppressing Treg cells.
23981747 Disease patterns of rheumatology outpatients seen in a tertiary hospital serving a multi-e 2013 Jun AIMS: To describe the spectrum of diseases seen in an outpatient setting in the Singapore General Hospital, the largest tertiary referral centre in Singapore. METHODS: In this cross-sectional study, medical records of patients scheduled for an appointment at the rheumatology specialist outpatient clinics over a 4-month period (10 August 2010-31 December 2010) were reviewed. Primary diagnoses documented by the attending physician at the latest visit were recorded. RESULTS: Among 4180 patients (29.5% male; mean [SD] age: 53.5 [15.1] years; 77.0% Chinese, 8.0% Malay, 8.8% Indian and 6.2% others), the spectrum of diseases seen was as follows [disease - definite n (%), probable n (%)]: Arthritis: rheumatoid arthritis - 958 (22.9%), 68 (1.6%); osteoarthritis - 452 (10.8%), 39 (0.9%); crystal arthritis - 417 (10.0%), 18 (0.4%); spondyloarthritis - 227 (5.4%), 61 (1.5%); psoriatic arthritis - 158 (3.8%), 9 (0.2%); other inflammatory arthritis - 153 (3.7%), 94 (2.2%); Connective tissues diseases: systemic lupus erythematosus - 412 (9.9%), 26 (0.6%); vasculitis - 105 (2.5%), 22 (0.5%); Sjögren's syndrome - 81 (1.9%), 32 (0.8%); overlap syndromes - 73 (1.8%); scleroderma - 50 (1.2%), 4 (0.1%); undifferentiated connective tissue diseases - 45 (1.1%), 106 (2.5%); myositis - 41 (1.0%), 12 (0.3%); antiphospholipid syndrome - 22 (0.5%), 7 (0.2%); polymyalgia rheumatica - 16 (0.4%); Others: soft tissue rheumatism - 155 (3.7%); osteoporosis - 61 (1.5%); other non-rheumatologic conditions - 189 (4.5%); other rheumatologic conditions - 67 (1.6%). CONCLUSION: Rheumatoid arthritis, osteoarthritis and crystal arthritis were the three most common rheumatological diseases seen in a tertiary referral centre serving a multi-ethnic urban Asian population in Singapore.
22280240 Inflammation-associated changes in bone homeostasis. 2012 Jun Bone is a dynamic tissue undergoing constant remodelling and repair. Its homeostasis is regulated by a coordinated process executed by bone forming and bone resorbing cells. Apart from being a major component of the locomotive system, bone provides protection for internal organs and represents a main mineral storage. Furthermore, it houses the haematopoietic system and is hence essential for the body's immune response. In turn, the innate and adaptive immune system itself, critically affect bone homeostasis. This is most evident during chronic inflammatory diseases, such as Rheumatoid Arthritis, where bone mass is critically reduced. Recently the field of osteoimmunology, focusing on this crosstalk between the immune system and bone homeostasis, has gained increasing attention. This review will highlight cellular and molecular mechanisms linking the innate and adaptive immune response to bone biology and provide an overview about involved cytokines and cells. Moreover, chronic inflammation and its consequences for bone turnover are discussed.
22175542 Tissue-specific expression of human calcineurin-binding protein 1 in mouse synovial tissue 2012 Jan Calcineurin (CN) is a calcium- and calmodulin-dependent serine/threonine phosphatase. In immune cells, CN controls the activity of a wide range of transcription factors, including nuclear factor of activated T, nuclear factor-kappa B, c-fos, and Elk-1. CN plays an important role in synoviocyte activation and arthritis progression in vivo and this function is tightly linked to dysregulated intracellular Ca(2+) store and Ca(2+) response triggered by proinflammatory cytokines. In the present study, transgenic mice expressing human calcineurin-binding protein 1 (hCabin1) were generated, driven by type II collagen promoter, and the efficiency of these mice was investigated by experimental arthritis. These transgenic mice successfully expressed hCabin1 in joint tissue as well as other organs such as liver, heart, and brain. The overexpression of hCabin1 reduced the disease severity during collagen-induced arthritis. In fibroblast-like synoviocytes (FLSs) from hCabin1 transgenic mice, the productions of these cytokines, including interleukin (IL)-2, IL-4, and IFN-γ, were decreased and matrix metalloproteinases were also depressed in transgenic mice FLS. In addition, these effects were only found in the joint tissue, which is a major inflammation site. These findings will provide a better knowledge of the pathogenic mechanisms of rheumatoid arthritis and a potential animal model of the chronic inflammatory conditions, including atherosclerosis and transplantation.
21931941 Satisfaction and attitudes toward therapy in patients with rheumatoid arthritis. 2012 Jun We examined associations between patient satisfaction and data obtained in routine clinical practice, and associations with therapeutic attitude in patients with rheumatoid arthritis (RA). A total of 220 patients with RA were enrolled in this cross-sectional evaluation. Demographic data, current disease state of RA, history of adverse events and self-reported questionnaire of patient satisfaction, attitudes toward therapy and reasons for being unwilling to change therapy were collected and analyzed. Multiple linear regression was used to identify characteristics. Age, Stanford Health Assessment Questionnaire (HAQ) score, and a visual analogue scale score of general health were the dominant correlates of satisfaction. Among the participants, 70% reported that they would not want to change therapy. The main reasons given were satisfaction with the current disease state (58%) and concern about the risk of side effects if therapy were to be changed (34%). Patients who were unwilling to change therapy due to concerns about side effects of new drugs did not have a significantly higher frequency of a past history of side effects, but showed significantly higher disease activity and a lower level of satisfaction with therapy. To summarize, patient satisfaction was associated with the HAQ. Patients who worried about the risk of side effects showed poor physical function and higher disease activity.