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ID PMID Title PublicationDate abstract
17472988 Associations between the PTPN22 1858C->T polymorphism and radiographic joint destruction i 2007 Dec OBJECTIVE: To investigate whether the PTPN22 1858T risk variant is associated with the rate of radiographic progression in rheumatoid arthritis (RA). METHODS: A longitudinally followed cohort of 238 Norwegian patients with RA (the EURIDISS cohort) was genotyped for the PTPN22 1858C-->T polymorphism. Radiographic damage was assessed by hand radiographs at baseline and after 1, 2, 5 and 10 years, and the radiographs were scored with the Sharp method modified by van der Heijde (Sharp-van der Heijde score) by a single experienced reader. Baseline serum levels of rheumatoid factor and anti-cyclic citrullinated peptide autoantibodies were also examined. RESULTS: The reported association between RA susceptibility and carriage of the T allele (34.4% in patients vs 21.4% in controls; odds ratio 1.92, 95% confidence interval 1.36 to 2.71, p = 0.0002) was confirmed. An association between annual progression rate of Sharp-van der Heijde score and T-allele carriers (p = 0.01),was also found, which was also present when only patients positive for the shared epitope were analysed (p = 0.03). This association was also maintained in multivariate analyses adjusting for shared epitope and demographic variables. CONCLUSIONS: An association between the PTPN22 risk variant and increased progression rate for structural damage was found. The results indicate that the PTPN22 gene may not only be associated with disease susceptibility, but also with disease progression.
17444583 Acute exacerbation of preexisting interstitial lung disease after administration of etaner 2007 May A 70-year-old woman with a 6-year history of seropositive rheumatoid arthritis (RA) and asymptomatic interstitial lung disease (ILD) began taking etanercept for ongoing arthritis despite treatment with methotrexate (MTX) and bucillamine. MTX was discontinued before introduction of etanercept. She developed lung injury 8 weeks after starting etanercept. Etanercept was discontinued and oral prednisolone 40 mg/day was begun, and her clinical findings gradually improved. Lung injury, although rare, is a recently noticed, potentially fatal adverse effect of all 3 licensed biological anti-tumor necrosis factor (TNF) agents. We recommend caution in the use of anti-TNF agents in elderly RA patients with preexisting ILD.
16465615 Treatment of rheumatoid arthritis in the 21st century: targeting B-lymphocytes. 2006 Jan Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by persistent inflammation of synovial tissue. Although the initiating event of RA is still unknown, recent research has demonstrated the importance of the increased production of tumor necrosis factor (TNF) alpha in the perpetuation of the inflammatory process of this disease. Targeting this molecule with soluble receptors, i.e., etanercept, or antibodies, like infliximab or adalimumab, a new class of highly effective anti rheumatic drugs has been developed. Unfortunately, not all patients respond sufficiently to TNF blockade and some of the patients become unresponsive to TNF-blocking agents. Targeting B-lymphocytes in these patients has opened a new therapeutic window. It has been demonstrated that B-lymphocytes have an important impact in the pathophysiology of RA. These cells produce not only a variety of autoantibodies, but directly stimulate autoaggressive T lymphocytes in the synovium. Furthermore, B-lymphocytes produce a variety of proinflammatory cytokines that also activate monocytes and synoviocytes. Several placebo-controlled clinical trials have demonstrated the efficacy of B-lymphocyte-directed therapy in patients that have responded poorly to conventional disease-modifying drugs or TNF blockade. In addition, several other B-cell specific antigens are potential targets in different autoimmune diseases.
17042013 Measuring sensation in the feet of patients with rheumatoid arthritis. 2006 Mar OBJECTIVES: (1) To determine the test-retest reliability of monofilaments pressed against the skin as a method of assessing sensation in the feet of patients with rheumatoid arthritis (RA) and in controls using two grades of monofilaments; (2) to determine the stability of findings over 6 weeks; and (3) to calculate initial estimates of frequency of loss of sensation and to investigate its association with disease status. METHOD: Clinical examination of the feet was undertaken in 51 patients with RA and 20 normal controls. Six sites on each foot were tested twice with both 10 g and 3 g research grade monofilaments and this was repeated after 6 weeks. Disease status was measured using the Disease Activity Score, the Health Assessment Questionnaire, visual analogue scales of pain, and the acute phase response using erythrocyte sedimentation rate and plasma viscosity. RESULTS: Reproducibility was high for 3 g (kappa=0.73) and 10 g (kappa=0.75) monofilaments. The best balance between sensitivity (58.8%) and specificity (87.5%) for distinguishing the feet of patients from the feet of controls was using the 3 g filament and defining reduced protective sensation as being sensitive to less than 11 of 12 applications. Using this definition, the prevalence of reduced protective sensation is 59% in the patient group and 12.5% in the feet of controls. There was some variation in sensation over 6 weeks in the patient group, but this was not related to measures of clinical status. CONCLUSION: The use of monofilaments in assessing sensation levels in the RA foot is repeatable and reproducible over a six-week period and requires only a short time to perform. The frequency of reduced sensation in the feet of patients with RA was greater than previously reported. Future studies should assess relationships with disease duration and inflammatory status.
18322992 Serum amyloid A activates nuclear factor-kappaB in rheumatoid synovial fibroblasts through 2008 May OBJECTIVE: Rheumatoid arthritis (RA) is a chronic, symmetric polyarticular joint disease and serum amyloid A (SAA) is an acute-phase protein that is upregulated during the course of RA. We investigated the role of SAA in the pathogenesis of RA. METHODS: Fibroblast-like synovial cells (FLS) were established from RA joints. SAA-stimulated expression of cytokines from FLS was evaluated by ELISA. Nuclear factor-kappaB (NF-kappaB) activation by SAA was evaluated by luciferase assay. NF-kappaB activation and IkappaBalpha degradation were evaluated by Western blotting and nuclear localization of p65 subunit of NF-kappaB in FLS. Expression of receptor for advanced glycation end-products (RAGE) in synovial tissue was evaluated by immunohistochemical study. Effects of preincubation of soluble RAGE on NF-kappaB activation by SAA was evaluated by Western blotting of IkappaBalpha. RESULTS: SAA stimulated the transcriptional activation by NF-kappaB in a dose-dependent manner and induced expression of the proinflammatory cytokines interleukin 6 (IL-6) and IL-8. Higher expression of RAGE in synovial tissue from patients with RA was noted. SAA induced IkappaBalpha degradation, with the peak effect around 30 minutes. Preincubation of SAA with soluble recombinant RAGE protein prevented SAA-induced IkappaBalpha degradation. SAA stimulation promoted nuclear translocation of NF-kappaB, whereas preincubation of SAA with RAGE inhibited nuclear translocation. CONCLUSION: Our data suggested that the SAA-RAGE-stimulated NF-kappaB signaling pathway has an important role in the pathogenesis of RA.
17409364 Costs of rheumatoid arthritis: new estimates from the human capital method and comparison 2007 Mar BACKGROUND: Individuals' valuation of changes in health states in monetary terms have been measured by examining changes in the direct and indirect costs of disease and by the willingness-to-pay (WTP) methodology. METHODS: In 2002, a 2-part study was conducted in Quebec. In one part of the study, 121 rheumatoid arthritis (RA) patients from the McGill University Health Centre were mailed the Stanford Cost Assessment Questionnaire, which enabled the elicitation of direct costs and indirect costs, according to the friction cost and the human capital methods. The other part was a phone survey conducted in a representative sample of the general population and in the same sample of patients, aiming to elicit the societal WTP for a complete cure of RA in the context of 2 different scenarios: a public coverage or private insurance. These estimates were then compared. RESULTS: Estimates of the cost of illness of RA ranged from 11,717 to 28,498 Canadian Dollars (CAD) depending on the method. These estimates are higher than those previously published in Canada from the 1990s, which is partly due to the recent and costly biological therapies and to a change in the measurement of productivity losses. These estimates are somewhat lower than the societal WTP elicited from the WTP survey, that is, 26,717 and 36,817 CAD per RA case, depending on the public or private health insurance context in which the cure would be available. CONCLUSION: Given that neither method is ideal, data from both methods would provide an important sensitivity analysis when monetary estimates of health state changes are required.
19015209 Early occupational therapy programme increases hand grip strength at 3 months: results fro 2009 Mar AIM: The goal of occupational therapy (OT) is to facilitate adjustments to lifestyle and to prevent function loss. This study evaluated the effects of an early OT programme in early rheumatoid arthritis (RA). METHODS: We conducted a randomised, blind, controlled trial enrolling 60 patients with early RA, divided into 2 groups. At baseline, group 1 received the full information programme and group 2 received no information. In an extension phase, patients in group 2 received the full information programme at 3 months and were assessed at 6 months. The main outcomes were grip strength of hands (as objective assessment) and Health Assessment Questionnaire (HAQ) score (as subjective assessment). RESULTS: At 3 months, grip strength of the dominant and non-dominant hands increased more in group 1 than in group 2 (p = 0.021 and 0.047 respectively). HAQ score decreased more in group 1 than in group 2 (p<0.001). In the extension phase, changes in grip strength and HAQ score in group 2 were similar to those seen in group 1 between baseline and 3 months. CONCLUSIONS: This study comparing two schedules of OT programme showed that an early extended information programme improved hand function in patients with early RA.
18789914 Mitochondrial depolarisation and oxidative stress in rheumatoid arthritis patients. 2008 Nov OBJECTIVES: To investigate mitochondrial membrane integrity, lipid peroxidation and cytotoxicity in peripheral lymphocytes (PL) from rheumatoid arthritis (RA) patients. DESIGN AND METHODS: South African black RA patients (HIV(-)) were recruited into the study. Mitochondrial membrane potential (Deltapsi(m)) was analysed in PL using the JC-1 dye distribution assay and flow cytometry. Correlations between Deltapsi(m) and clinical parameters were tested for statistical significance. Cytotoxicity (LDH) and lipid peroxidation (thiobarbituric acid reactive substances (TBARS)) was also determined. RESULTS: Our findings show significantly elevated levels of cytotoxicity (p=0.0029) and lipid peroxidation (p=0.0030) in RA. A significantly higher percentage of circulating PL contained depolarised mitochondria (p=0.0003) which correlated with disease activity and C-reactive protein levels in patients. Collapse of Deltapsi(m) also negatively correlated to absolute lymphocyte counts (r=-0.4041; p=0.0197). CONCLUSION: These findings suggest a possible role for mitochondrial membrane alterations in the pathology of RA.
18037688 Inter-observer agreement of standard joint counts in early rheumatoid arthritis: a compari 2008 Jan OBJECTIVES: The aims of the present study were to assess the inter-observer agreement of standard joint count and to compare clinical examination with grey scale ultrasonography (US) findings in patients with early rheumatoid arthritis (RA). METHODS: The study was conducted on 44 RA patients with a disease duration of <2 yrs. Clinical evaluation was performed independently by two rheumatologists for detection of tenderness in 44 joints and swelling in 42 joints. All patients underwent US assessment by a rheumatologist experienced in this method and blinded to the clinical findings. Joint inflammation was detected by US when synovial fluid and/or synovial hypertrophy was identified using OMERACT preliminary definitions. The inter-observer reliability was calculated by overall agreement (percentage of observed exact agreement) and kappa (kappa)-statistics. The reliability of US was calculated in 12 RA patients. RESULTS: There was fair to moderate inter-observer agreement on individual joint counts for either tenderness or joint swelling apart from the glenohumeral joint. US detected a higher number of inflamed joints than did clinical examination. The mean (+/-S.D.) US joint count for joint inflammation was 19.1 (+/-4.1), while the mean (+/-S.D.) number of swollen joints was 12.6 (+/-3.6), with a significant difference of P = 0.01. CONCLUSIONS: Our results provide evidence in favour of the hypothesis that clinical examination is far from optimal for assessing joint inflammation in patients with early RA. Furthermore, this study suggests that US can considerably improve the detection of signs of joint inflammation both in terms of sensitivity and reliability.
18270855 Share epitope, citrullinated cyclic peptide antibodies and smoking in Brazilian rheumatoid 2008 Feb The events involved in the pathogenesis of rheumatoid arthritis (RA) still remain unclear, but certainly the etiology is multifactorial. Shared epitope (SE) of HLADRbeta1 is the most important genetic risk factor. Environmental risk factors are less understood. Smoking is a candidate, associated with the rising of citrullinated cyclic peptide antibodies (anti-CCP). Anti-CCP antibodies are highly specific for RA. In this study, we investigated whether the association between anti-CCP production and smoking was influenced by carriage of SE in a highly miscegenated population of patients with RA. One hundred Brazilian patients were inquired about cigarette smoking. For all of them, DNA for HLA typing and serum to anti-CCP antibodies quantification were obtained. Forty-two were smokers and 58 were nonsmokers. The SE was present in 61 patients and the anti-CCP was positive in 71 patients. We found that, among smokers, 25 were SE-positive, 22 presented with anti-CCP and 3 without anti-CCP, and 17 were SE-negative, 9 presented with anti-CCP and 8 without anti-CCP (OR 6.5, 95% CI 1.40 to 30.20). These results suggest that environmental factors contribute to the raising of anti-CCP in individuals with HLA background to RA, smoking being a strong candidate.
16870095 Anti-cyclic citrullinated peptide antibody in rheumatoid arthritis: relation with disease 2006 May OBJECTIVES: To analyse the value of the anti-cyclic citrullinated peptide antibody (anti-CCP) in patients with rheumatoid arthritis (RA) as a prognostic factor, as well as its relationship with disease activity. METHODS: A cross-sectional study was made on 89 patients with RA. The following values were assessed: erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), anti-CCP, Disease Activity Score 28 (DAS 28), Modified Health Assessment Questionnaire score (M-HAQ) and simplified radiologic score of Sharp/Van der Heijde (SENS: simple erosion narrowing score). RESULTS: Sixty-four percent of the patients were anti-CCP positive, from which 36.8% were negative for RF. Among negative RF patients, 48.3% had anti-CCP antibody. The average value of DAS 28 in anti-CCP positive patients was 4.31 (SD 1.27) compared to 3.30 (SD 1.55) for anti-CCP negative (p 200 U/ml) had higher SENS (p < 0.05). There was no correlation between M-HAQ and anti-CCP. CONCLUSION: Prevalence of anti-CCP was higher among patients with higher activity. Patients with higher levels of anti-CCP antibody had more aggressive disease, with greater activity (elevated values in DAS 28 and CRP) and more severe radiological damage (more erosions and higher radiological damage, SENS).
16572445 Association of tumor necrosis factor alpha polymorphism, but not the shared epitope, with 2006 Apr OBJECTIVE: To determine whether the tumor necrosis factor alpha (TNFA) -308 guanine-to-adenosine polymorphism and/or the shared epitope (SE) is associated with radiographic damage in patients with early rheumatoid arthritis (RA). METHODS: The cohort consisted of 189 patients with early seropositive RA (median 5.6 months since symptom onset) who had active disease, no previous disease-modifying antirheumatic drug treatment, and >or=2 sets of scored radiographs of the hands/wrists and forefeet. TNFA -308 polymorphism was analyzed by polymerase chain reaction pyrosequencing. The SE was defined as presence of any 1 of the following HLA-DRB1 alleles: *0101, *0102, *0401, *0404, *0405, *0408, *0410, *1001, *1402, or *1406. Radiographic progression was assessed by the total Sharp score. RESULTS: Using a weighted least-squares regression analysis, patients with the -308 TNFA AA plus AG genotypes (n=49) had significantly higher rates of progression in erosion scores (median 0.84 versus 0.48 units/year), joint space narrowing (JSN) scores (0.42 versus 0.04), and total Sharp scores (1.70 versus 0.61) compared with patients with the TNFA GG genotype (n=140). Presence of the SE (n=137) was associated with significantly lower progression rates (per year) for total Sharp scores (median 0.9 versus 1.25 units/year) and JSN scores (0.04 versus 0.41), but not for erosion scores (0.50 versus 0.61) compared with patients without the SE (n=52). In a least-squares multiple linear regression model, the presence of the AA plus AG genotypes was associated with a significantly higher progression rate after adjusting for the presence of the SE, interaction between the SE and the AA plus AG genotypes, baseline log C-reactive protein level, Health Assessment Questionnaire Disability Index, total Sharp score, swollen joint count, and presence of osteophytes (osteoarthritis). There was a strong linkage disequilibrium between DRB1*0301 and TNFA polymorphism (D'=0.84, r2=0.45, P<0.001). CONCLUSION: This study showed an association between the TNFA -308 polymorphism and progression of radiographic damage in patients with early seropositive RA. This association appeared to be independent of the SE, but might be dependent on other genetic variants in linkage disequilibrium with the -308 TNFA A allele and DRB1*0301. Further studies should be conducted to validate these results in both longitudinal observational cohorts and randomized clinical trials.
17541497 Use of complementary and alternative medicine by rheumatoid arthritis patients in Korea. 2008 Jan This study measured the prevalence of use of complementary and alternative medicine (CAM) in Korean patients with rheumatoid arthritis (RA). A trained nurse conducted 20-min questionnaire-based interviews at the hospitals when each patient visited as an outpatient. The questionnaire included questions on demographic information, clinical information, and the use of CAM. Of the 153 respondents, 125 (82%) had used CAM; 37% of those who used CAM had started taking CAM products following suggestions from family members and other relatives. In users of CAM, 35% considered that it improved the symptoms of RA, and 14% felt it was effective in achieving psychological relaxation. We categorized treatment into six CAM categories used by the respondents: 84.0% of patients used traditional Oriental medical treatments, 70.4% used plant- and animal-derived over-the-counter health care products, and 13.6% used manual therapies. Most RA patients (64%) would like to try a new type of CAM. About half of the respondents (48%) expected to receive information about CAM from their general practitioner even if most (72%) did not discuss their use of CAM with their doctor. Most of the RA patients in this study used CAM, and half reported beneficial effects. Despite the presence of adverse side effects, patients tended to use CAM without discussing it with their main physicians, suggesting that physicians should be actively involved in the prescription and use of CAM.
16915981 Management of shoulder hemiarthroplasty in a patient with rheumatoid arthritis. 2006 Aug STUDY DESIGN: Case report. BACKGROUND: Rehabilitation after shoulder hemiarthroplasty for rotator cuff tear arthropathy (RCTA) represents a significant challenge to physical therapists. Limited goals have been defined for this patient population and include no pain or slight pain at rest, moderate pain with vigorous activity, shoulder external rotation active range of motion (AROM) greater than 20 degrees, and shoulder abduction AROM greater than 90 degrees. CASE DESCRIPTION: The patient was a 60-year-old female elementary school teacher with functional class III adult-onset rheumatoid arthritis, who came to physical therapy 2 weeks after undergoing a hemiarthroplasty for RCTA of the right shoulder. Physical therapy included 33 treatment sessions involving 4 to 11 exercises each session. All sessions were performed under the direct supervision of a physical therapist utilizing specially designed equipment. Physical therapy emphasized early active assisted elevation range of motion (ROM), graded progressive exercise, and functional training. All exercises were performed in a pain-free ROM or a ROM that did not increase shoulder pain. OUTCOMES: Following physical therapy, subjective pain scale at rest was 0/10 and during vigorous activity 1/10 to 2/10. Shoulder AROM was normal and shoulder rotation and elevation strength was good. There was a significant improvement in shoulder proprioception and the patient demonstrated a negative belly press test for subscapularis muscle integrity. Additionally, the patient's score on the self-report section of the American Shoulder and Elbow Surgeons Assessment Form increased from 0% at the initial examination to 70% at discharge. DISCUSSION: Despite limited expectations, this patient achieved normal shoulder ROM and near normal shoulder strength after 14 weeks of physical therapy. Overall, an early, aggressive, progressively graded exercise program appears to be a safe and effective form of treatment after shoulder hemiarthroplasty for RCTA.
17134492 The pendulum test as a tool to evaluate passive knee stiffness and viscosity of patients w 2006 Nov 29 BACKGROUND: The pendulum test of Wartenberg is a technique commonly used to measure passive knee motion with the aim to assess spasticity. We used this test to evaluate changes of the knee angular displacement, passive stiffness and viscosity in rheumatoid arthritis patients. Stiffness and viscosity represent passive resistances to joint motion associated with the structural properties of the joint tissue and of the muscular-tendon complex. Stiffness can be considered an intrinsic property of the tissues to resist deformation, while viscosity is related to cohesive forces between adjacent layers of tissues. Both parameters may influence the joint range of motion affecting angular displacement. METHODS: Nine women with rheumatoid arthritis were compared with a group of healthy women. With the subject half-lying, the relaxed knee was dropped from near-full extension and the characteristics of the ensuring damped unsustained knee oscillation evaluated. The kinematics of leg oscillations was recorded using ultrasonic markers (Zebris CMS HS 10) and the kinetic data were calculated from kinematic and anthropometric measures. RESULTS: Knee stiffness significantly increased (p < 0.001) in patients with respect to the control group, while differences in viscosity were not significant. Moreover, the amplitudes of first knee flexion (the maximal flexion excursion after knee release) and first knee extension (the maximal extension excursion after the first knee flexion) were significantly decreased (p < 0.001). A regression analysis showed that disease severity correlated moderately with stiffness (R2 = 0.68) and first flexion (R2 = 0.78). Using a multivariate regression, we found that increasing stiffness was the main factor for the reduction of flexion and extension motions. CONCLUSION: We showed that the Wartenberg test can be considered a practical tool to measure mechanical changes of knee caused by rheumatoid arthritis. This novel application of Wartenberg test could be useful to follow up the effects of pharmacological and rehabilitative interventions in this disease.
17713879 [Spontaneous tongue necrosis consecutive to rheumatoid hyperviscosity syndrome. A case rep 2008 Jan BACKGROUND: Because the tongue is an organ known for its excellent blood supply, ischaemic lingual necrosis is extremely rare within clinical everyday life. Acute lingual circulatory disturbances can result from impairment of venous drainage or more often from ischaemic arterial occlusion. Due to permanent function loss of the tongue, apparent lingual necrosis may lead to severe mutilation of the patient. While vasculitis of the lingual arteries in temporal arteritis is said to be the most frequent causation of tongue necrosis, diagnosing the underlying disease of lingual ischaemia may sometimes be challenging for the clinician. PATIENTS AND METHODS: We present the first reported case of a spontaneous lingual necrosis in a patient with rheumatoid arthritis, due to polyclonal gammopathy with extensive hyperviscosity syndrome and local vasculitis. RESULTS: Clinical symptoms, diagnosis and therapy of tongue necrosis are presented in a case report. Besides an overview on the disorder of hyperviscosity syndrome, the discussion will illustrate pathogenetic, diagnostic and therapeutic considerations of lingual ischaemia. The international medical literature is reviewed to summarize the causes of tongue necroses that are described up to now. The particular importance of temporal arteritis Horton for the otolaryngologist in general and for the development of lingual necrosis in particular is highlighted. CONCLUSIONS: Apart from the presentation of the first reported case of lingual necrosis in rheumatoid hyperviscosity syndrome, the intention of this article is to draw the clinician's attention on the fundamental aspects of lingual ischaemia and of temporal arteritis.
17804530 Surface expression of fractalkine receptor (CX3CR1) on CD4+/CD28 T cells in RA patients an 2007 Jun Rheumatoid arthritis (RA) is associated with accelerated atherosclerosis. Fractalkine, a CX3C/chemokine (CX3CL1), mediates monocytes-macrophage infiltration in activated endothelium, suggesting its specific role in atherosclerosis-related inflammation. In this study, we evaluate the following in early RA patients: the expression of fractalkine receptor (CX3CR1) on CD4+/CD28- T cells, a subset involved in atherosclerotic infiltration; the correlation between this subset and validated markers of early atherosclerosis. CD4+ T cells were isolated by immunomagnetics beads in 50 early RA patients and 26 healthy controls (HC). After isolation, CD4+/CD28-/CX3CR1+ T lymphocytes were assessed by FACS analysis. Endothelial dysfunction was evaluated by both carotid intima-media thickness (IMT) and flow-mediated vasodilation (FMV). We observed: a higher expansion of CD4+/CD28- subset in RA patients when compared to HC (7.7%, 5.15-9.7 vs. 0.7%, 0.2-1.5, P < 0.01; respectively); this expansion directly correlated with increased IMT (0.91 mm, 0.5-1.3 vs. 0.7 mm, 0.2-1, P < 0.01; RA vs. C, respectively) and inversely correlated with FMV (3.5%, 1.7-7 vs. 9%, 3.5-11, P < 0.01; RA vs. C, respectively); the large majority of CD4+/CD28-, in RA, coexpressed CX3CR1 (93%, 67-99 vs. 30%, 10-48, P < 0.01; RA vs. C, respectively); this expansion significantly correlated with both the parameters of premature vascular damage and DAS 28. Our data suggest that CX3CL1/CX3CR1 axis might play a role in the induction and development of the endothelial dysfunction during RA.
17477484 Rationale and strategies for reevaluating the ACR20. 2007 May OBJECTIVE: To assess whether the American College of Rheumatology response criteria ACR20 should be replaced by another definition of response with enhanced discriminant validity. METHODS: We worked with statisticians to define over 100 different ways of defining response, including dichotomous definitions (e.g., ACR20; ACR50; ACR70; low disease activity), ordinal definitions (EULAR response; ACR20, ACR50, ACR70), disease activity indexes [Disease Activity Score (DAS); Disease Activity Index, SDAI], continuous definitions (mean percentage improvement in all core set measures; nACR, ACRn), and hybrid definitions (ACR20, ACR50, ACR70 defined for a patient as 0, 1, 2, 3 scale with continuous measures between intervals) along with variations on each of these approaches (e.g., percentage vs absolute change in DAS; e.g., measures requiring vs not requiring joint count improvement). To test clinical validity, we administered a survey using patients from a trial who had various levels of improvement and asked rheumatologists whether and by how much these patients improved. For Sn-to-Chge, we are collecting data from large disease modifying antirheumatic drug multicenter trials in rheumatoid arthritis and ranking candidate definitions of response on their average p values in distinguishing active treatment from placebo or combination compared to single comparator. RESULTS: We surveyed 52 rheumatologists about which trial patients had improved and by how much. Trial data were obtained and tested for sensitivity to change. CONCLUSION: A rigorous data-driven consensus process was used to reassess the ACR20.
16458876 High redox thioredoxin but low thioredoxin reductase activities in the serum of patients w 2006 May BACKGROUND: Thioredoxin (Trx)/thioredoxin reductase (TrxR) is a redox-active system induced by oxidative stress. We investigated its status as a function of RA disease activity. METHODS: 64 consecutive RA patients and 27 healthy subjects were enrolled in the study. Serum Trx protein levels were evaluated using an immunoassay and immunoblot, while redox Trx and TrxR activities and oxidative stress markers (carbonyl groups, thiols), were determined using spectrophotometric methods. RESULTS: Redox Trx activity and Trx protein concentrations were significantly higher in RA patients than in controls (redox Trx activity: 37.7+/-22.6 versus 21.1+/-7.9 ng/mL, p<0.01; Trx protein: 25.5+/-12.0 versus 12.3+/-5.1 ng/mL, p<0.0001). Redox Trx activity correlated with the DAS score (r=0.45, p=0.004) and with the tender joint count (r=0.49, p=0.002) whereas there was no correlation with Trx protein concentrations. Immunoblot analysis showed that circulating Trx was partially aggregated. TrxR activity was lower in the serum of RA patients than in healthy subjects (197+/-70 versus 263+/-56 U/L, p=0.002). TrxR activity was correlated with the DAS score (r=0.53, p<0.001) and with the tender joint count (r=0.36, p<0.01). There were no correlations between oxidative stress marker levels and redox Trx activity, Trx protein concentrations or TrxR activity. CONCLUSION: Redox Trx and TrxR activities correlated with the disease activity of RA patients consistent with the hypothesis that Trx/TrxR activities may contribute to disease activity in RA.
17951651 Immunohistochemistry of the inflamed synovium. 2007 The development in the techniques for obtaining synovial tissue biopsy, especially through arthroscopy, have resulted in greater access to high-quality synovial tissue. The use of immunohistochemistry in arthritis research has greatly furthered our understanding of the varied immunological and biochemical pathways involved in inflammatory arthropathopies such as rheumatoid and psoriatic arthritis. Immunohistochemistry provides a strikingly visual narrative of the essential elements involved in inflammatory arthritis, from the infiltrating inflammatory cells (e.g., T-cells, macrophages, B-cells, and neutrophils), their products (e.g., cytokines, metalloproteinases) and their varied receptor molecules. This chapter describes the standard three-stage immunoperoxidase technique used in our laboratory and widely in the literature. Some problems that may be encountered and how they may be overcome are commented on. Also described is a method for dual-labeled immunofluoresence staining.