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ID PMID Title PublicationDate abstract
19644849 Golimumab, a human anti-tumor necrosis factor alpha monoclonal antibody, injected subcutan 2009 Aug OBJECTIVE: To assess the safety and efficacy of golimumab in methotrexate (MTX)-naive patients with active rheumatoid arthritis (RA). METHODS: MTX-naive patients with RA (n = 637) were randomized to receive placebo plus MTX (group 1), golimumab 100 mg plus placebo (group 2), golimumab 50 mg plus MTX (group 3), or golimumab 100 mg plus MTX (group 4). Subcutaneous injections of golimumab or placebo were administered every 4 weeks. The dosage of MTX/placebo capsules started at 10 mg/week and escalated to 20 mg/week. The primary end point, the proportion of patients meeting the American College of Rheumatology 50% improvement criteria (achieving an ACR50 response) at week 24, required significant differences between groups 3 and 4 combined (combined group) versus group 1 and significant differences in a pairwise comparison (group 3 or group 4 versus group 1). RESULTS: An intent-to-treat (ITT) analysis of the ACR50 response at week 24 did not show a significant difference between the combined group and group 1 (38.4% and 29.4%, respectively; P=0.053), while a post hoc modified ITT analysis (excluding 3 untreated patients) of the ACR50 response showed statistically significant differences between the combined group and group 1 (38.5% versus 29.4%; P=0.049) and between group 3 (40.5%; P=0.038) but not group 4 (36.5%; P=0.177) and group 1. Group 2 was noninferior to group 1 for the ACR50 response at week 24 (33.1%; 95% confidence interval lower bound -5.2%; predefined delta value for noninferiority -10%). The combination of golimumab plus MTX demonstrated a significantly better response compared with placebo plus MTX in most other efficacy parameters, including response/remission according to the Disease Activity Score in 28 joints. Serious adverse events occurred in 7%, 3%, 6%, and 6% of patients in groups 1, 2, 3, and 4, respectively. CONCLUSION: Although the primary end point was not met, the modified ITT analysis of the primary end point and other prespecified efficacy measures demonstrated that the efficacy of golimumab plus MTX is better than, and the efficacy of golimumab alone is similar to, the efficacy of MTX alone in reducing RA signs and symptoms in MTX-naive patients, with no unexpected safety concerns.
19585118 Successful treatment of refractory cardiac tamponade due to rheumatoid arthritis using per 2010 Jun Rheumatoid pericarditis occurs in patients with rheumatoid arthritis (RA). However, cardiac tamponade due to rheumatoid pericarditis is rare; we describe a case of a 72-year-old man with a 6-year history of rheumatoid arthritis who developed rheumatoid pericarditis with recurrent cardiac tamponade. The patient experienced relapse of the cardiac tamponade despite treatment with pericardiocentesis. Therefore, the patient underwent surgical pericardial drainage. The patient was also subsequently treated with increasing doses of corticosteroid, methotrexate and leukocytapheresis. These treatments resulted in a successful outcome without any complication. This case suggests that in addition to immunosuppressive therapy, pericardial drainage should be considered in the treatment of life-threatening refractory cardiac tamponade caused by rheumatoid arthritis.
20131291 Protection against anti-citrullinated protein antibody-positive rheumatoid arthritis is pr 2010 May OBJECTIVE: The protective effect of HLA-DRB1 alleles on the development of rheumatoid arthritis (RA) is poorly understood. The aim of this study was to perform a meta-analysis of 4 European populations to investigate which HLA-DRB1 alleles are associated with protection in anti-citrullinated protein antibody (ACPA)-positive RA and ACPA-negative RA. METHODS: Data for >2,800 patients and >3,000 control subjects for whom information on HLA-DRB1 typing and ACPA status was available were collected from 4 European countries: Norway, Sweden, The Netherlands, and Spain. The odds ratios (ORs) and 95% confidence intervals (95% CIs) associated with the different HLA-DRB1 alleles were analyzed in a combined meta-analysis focused on protective alleles and classifications. The analysis of ACPA-positive RA was stratified for the shared epitope (SE) alleles, to correct for skewing due to this association. RESULTS: In ACPA-positive RA, the only alleles that conveyed protection after stratification for SE were HLA-DRB1*13 alleles (OR 0.54 [95% CI 0.38-0.77]). The protective effect of the allele classifications based on the DERAA and D70 sequences was no longer present after exclusion of DRB1*13 (for D70, OR 0.97 [95% CI 0.75-1.25]), indicating that DRB1*13, rather than the DERAA or D70 sequence as such, is associated with protection. Among the DRB1*13 alleles, only DRB1*1301 was associated with protection (OR 0.24 [95% CI 0.09-0.59]). Protection appeared to follow a north-to-south gradient, with the strongest association in northern European countries. In ACPA-negative RA, there were no robust associations with HLA-DRB1 alleles. CONCLUSION: Our data do not support any of the classifications of protective alleles and indicate that protection against ACPA-positive RA is predominantly associated with HLA-DRB1*1301.
19370188 [Analysis of foot structural damage in rheumatoid arthritis: clinical evaluation by valida 2009 Jan OBJECTIVE: To examine foot involvement in rheumatoid arthritis (RA) and to characterize structural alterations in patients with anti-cyclic citrullinated peptide (CCP) antibody-positive and -negative disease. METHODS: Seventy-eight patients with RA with foot pain were consecutively enrolled. The Manchester Hallux Valgus (MHV) rating scale was used to evaluate the hallux valgus deformity degree. The Foot Posture Index (FPI6), a novel, foot-specific outcome measure, was adopted in order to quantify variation in the position of the foot. The findings were correlated with disease duration and presence or absence of anti-CCP antibodies. RESULTS: About 84.6% patients had different degrees of hallux valgus and 65.4% subjects had a pronated foot. These two foot alterations were prevalently found in patients with long-standing disease and circulating anti-CCP antibodies. On the contrary, RA patients without anti-CCP and early disease essentially displayed a supinated foot without relevant hallux valgus deformity. CONCLUSION: Our findings allowed to identify different anatomic foot alterations in RA patients according to disease duration and negative prognostic factors such as anti-CCP antibodies. Our findings support the role of an accurate analysis of foot structural damage and may suggest the usefulness of a correct plantar orthosis prescription also in early phases of the disease.
19289297 What can we learn from the presence of anti-cyclic citrullinated peptide antibodies in sys 2009 Oct BACKGROUND: Anti-cyclic citrullinated peptide (anti-CCP) antibodies have proved to be a specific marker for the diagnosis of rheumatoid arthritis (RA). However, the antibodies can also be detected in other rheumatic diseases, especially systemic lupus erythematosus (SLE). Recent studies have shown anti-CCP antibodies are associated with erosive arthritis in SLE patients. Since erosive arthritis is not common in SLE and many patients with non-erosive arthritis also have anti-CCP antibodies, the clinical significance of anti-CCP antibodies in SLE needs to be further studied. OBJECTIVE: To investigate the prevalence and clinical significance of anti-CCP antibodies in Chinese SLE patients. METHODS: Serum samples from 138 SLE patients were examined for anti-CCP with the second generation anti-CCP detection kit. The associations of anti-CCP with clinical and laboratory features, especially arthritis, in such SLE patients were analyzed. RESULTS: The prevalence of anti-CCP was 13.8% (19/138) in Chinese SLE patients. Seventy of 138 SLE patients had experienced arthritis, of whom 14 patients were anti-CCP+. Significantly, anti-CCP antibodies were more frequently found in SLE patients with arthritis than without arthritis (20% vs 7.4%, P<0.05). A statistical correlation between anti-CCP and rheumatoid factor (RF) was found in SLE patients with arthritis (r=0.36, P=0.002). The frequency of arthritis was significantly higher in SLE patients with anti-CCP than without (73.7% vs 47.1%,P<0.05). Eight out of 138 SLE patients showed joint erosions on radiographs. When compared with anti-CCP- patients, erosive arthritis occurred more often in anti-CCP+ patients (35.7% vs 5.4%, P<0.001). Interestingly, two patients without anti-CCP and RF who had erosive arthritis were anti-RA33 antibodies positive. All of 8 SLE patients with erosive arthritis in our study fulfilled 1987 ACR criteria for RA. With regard to other clinical and laboratory features, there were no differences between SLE patients with arthritis and without or between anti-CCP+ patients and anti-CCP- patients. CONCLUSIONS: Anti-CCP antibodies have a frequency of 13.8% in Chinese SLE patients and its presence is closely associated with the onset of arthritis and bone erosion.
19029133 Lactoferrin is a survival factor for neutrophils in rheumatoid synovial fluid. 2009 Jan OBJECTIVES: Lactoferrin is an iron-binding protein that is released from activated neutrophils at sites of inflammation and has anti-microbial as well as anti-inflammatory properties. This study set out to determine whether lactoferrin can delay neutrophil apoptosis and could act as a survival factor for neutrophils in SF. METHODS: Human peripheral blood and SF neutrophils were incubated with iron-free lactoferrin and apoptosis determined after 9 h. SF from patients with RA was added to isolated neutrophils, with or without immunodepletion of lactoferrin, and effects on neutrophil apoptosis determined. Levels of lactoferrin in SF were assessed and related to disease duration and markers of disease activity. RESULTS: Iron-free lactoferrin significantly delayed apoptosis of peripheral blood neutrophils, in a concentration-dependent manner after 9 h in culture (P < 0.04). Lactoferrin could also delay apoptosis of neutrophils isolated from SF of patients with RA. SF from patients with established RA delayed apoptosis of peripheral blood neutrophils and this effect was significantly reduced by depletion of lactoferrin (P < 0.03). Lactoferrin levels in SF from patients with established RA did not correlate with disease severity, but did correlate with markers of inflammation (CRP) and with the presence of RF. SF from patients with arthritis of <12 weeks duration did not contain significant levels of lactoferrin. CONCLUSION: Lactoferrin contributes to extended neutrophil survival in the rheumatoid joint in the established phase of RA but not in very early arthritis.
20200013 New understanding and approaches to treatment in rheumatoid arthritis. 2010 Rheumatoid arthritis (RA) is the most common autoimmune inflammatory polyarthritis. Significant advances in the understanding of its pathogenesis have led in the past two decades to major advancement in its therapy. We used data from articles in Cochrane Database of Systematic Reviews on 'rheumatoid arthritis', meta-analyses and randomized controlled trials on adult RA (age >19 years) published in English within the past 5 years and identified in PubMed, and other key papers on management of RA. Appropriate, early and aggressive therapy is required for confirmed active cases of RA. The choice of disease-modifying drugs and different combinations, especially the newer biologic agents in regards of their early and long-term usage remains debated because of high costs and long-term safety concerns. Development of newer biologic agents working on different pathways of inflammation is underway in different stages. It remains to be determined how and when each of these agents will fit in the overall management of RA. Furthermore, post-marketing surveillance of the safety and response sustainability of these drugs is warranted.
21794790 [Descriptive study of the use of DMARD in patients with rheumatoid arthritis or persistent 2011 Mar INTRODUCTION: Rheumatoid arthritis is clinically very heterogeneous and variable in its progression, and no one treatment works the same for all patients, as this will depend on the clinical course and specific situations. OBJECTIVE: To describe the treatment with DMARDs established for the first time in patients with rheumatoid arthritis (RA) or persistent arthritis (PA) in routine clinical practice in Spain. MATERIAL AND METHODS: Epidemiological, cross-sectional, uncontrolled, multicenter study in 15 regions of Spain during a period of five months (July to November 2006). We included patients of both genders, aged 18 years and diagnosed with RA according to ACR criteria or PA defined as any arthritis (oligoarthritis or polyarthritis) lasting ≥12 weeks, which would be given DMARD to treat their disease. RESULTS: 1079 patients were recruited, 915 analyzed (33% ♂/♀ 67%) meeting all the criteria required to be evaluated in the study. Mean age of patients was 54.6 (SD=15.4) years. The mean time from onset of symptoms until the 1st visit with the rheumatologist was 6.3 (11.3) months and the time from the 1st visit with the rheumatologist and the start of treatment was 4 (13.5) months. Of the patients tested, 96.7% was treated with at least one DMARD, 62.1% were given NSAIDs, corticosteroids to 59.2% and 3.8% biological therapy. In patients who received DMARDs, 90.3% received treatment with a single DMARD, 9.5% with 2 DMARDs and 0.2% with three DMARDs. In polytherapy, the DMARDs that are most often administered together were MTX + hydroxychloroquine (4.8%), MTX + leflunomide (2.0%) and MTX + sulfasalazine (1.5%). The most frequently used DMARD in monotherapy was MTX (81.3%), followed by leflunomide (4.1%) and hydroxychloroquine (3.2%). In 89.6%, the treatment of first choice was adequate according to the SER. CONCLUSION: The most common pattern of initial treatment of RA is MTX monotherapy. Treatment of RA by rheumatologists has been homogenized in recent years.
20058046 Impact of biologics on the prevalence of orthopedic surgery in the National Database of Rh 2010 Jun The aim of this study was to investigate changes in the treatment strategy of rheumatoid arthritis (RA) and the prevalence of RA-related surgeries after approval of biologics in Japan and to analyze the impact of biologics on the incidence of orthopedic surgeries using a nationwide observational cohort database of rheumatic diseases [National Database of Rheumatic Diseases by iR-net in Japan (NinJa)]. The proportion of patients using biologics linearly increased from 2004 (1.8%) to 2007 (10.0%), but neither the number nor type of RA-related surgery significantly changed during this period. Patients treated with biologics exhibited relatively more severe disease activity and lower physical function. Among patients using biologics, those who underwent RA-related surgeries exhibited background characteristics of longer disease duration and worse physical function, while disease activity was not different from patients without surgery. These results suggest that the potential value of biologics in avoiding surgical procedure is limited in patients with severe functional disorders caused by long disease duration. Further investigation with a longer observation period is required to obtain more definite conclusions as to the impact of biologics usage on orthopedic surgeries.
21303479 Clinical factors related to the efficacy and complications of orthopedic surgery for rheum 2011 Feb AIMS: To determine what clinical factors relating to efficacy besides complications of orthopedic surgery for patients treated with anti-tumor necrosis factor (TNF)-α therapy (infliximab), we analyzed the clinical data of 52 cases of orthopedic surgery, such as total hip arthroplasy (THA), total knee arthroplasty (TKA), total shoulder arthroplasy (TSA), total elbow arthroplasty (TEA), arthroscopic synovectomy, foot arthroplasty, spine surgery, hand surgery and fracture. METHODS: We analyzed clinical factors including age, disease duration, preoperative C-reactive protein (CRP), disease activity score (DAS)-28, matrix metalloproteinase (MMP)-3, and rheumatoid arthritis particle-agglutination (RAPA) in 52 cases of rheumatoid arthritis (RA) undergoing orthopedic surgery. For complications of orthopedic surgery, signs of postoperative infection were recorded, including rubor, discharge, systemic infection and frequencies of wound dehiscence, as well as the incidence of any surgical complication requiring a secondary revision procedure were measured. RESULTS: Signs of infection or surgical complications occurred in two of 52 patients (3.8%). There is significant correlation between RAPA and improvement of CRP 3 months after surgery; however, there is no correlation between infection and clinical factors including age, disease duration, preoperative CRP, MMP-3, RAPA and the period until surgery after infliximab infusion. CONCLUSION: Infliximab did not increase the risk of either infections or surgical complications occurring in patients with RA within 1 year of orthopedic surgery. Improvement of CRP after surgery is likely to be due to infliximab for high RAPA in RA patients.
20213705 Bootstrap-based methods for estimating standard errors in Cox's regression analyses of clu 2010 Mar 30 We propose two bootstrap-based methods to correct the standard errors (SEs) from Cox's model for within-cluster correlation of right-censored event times. The cluster-bootstrap method resamples, with replacement, only the clusters, whereas the two-step bootstrap method resamples (i) the clusters, and (ii) individuals within each selected cluster, with replacement. In simulations, we evaluate both methods and compare them with the existing robust variance estimator and the shared gamma frailty model, which are available in statistical software packages. We simulate clustered event time data, with latent cluster-level random effects, which are ignored in the conventional Cox's model. For cluster-level covariates, both proposed bootstrap methods yield accurate SEs, and type I error rates, and acceptable coverage rates, regardless of the true random effects distribution, and avoid serious variance under-estimation by conventional Cox-based standard errors. However, the two-step bootstrap method over-estimates the variance for individual-level covariates. We also apply the proposed bootstrap methods to obtain confidence bands around flexible estimates of time-dependent effects in a real-life analysis of cluster event times.
19591638 Predicting the future of anti-tumor necrosis factor therapy. 2009 Tumor necrosis factor (TNF) antagonists are approved worldwide for the treatment of rheumatoid arthritis (RA). Clinical experience revealed that TNF-blocking therapy is effective for only approximately two thirds of patients, reflecting that there are 'responders' as well as 'nonresponders'. Given the destructive nature of RA, the risk of adverse effects, and considerable costs for therapy, there is a strong need to make predictions on success before the start of therapy. In the current issue of Arthritis Research & Therapy, Hueber and colleagues become the first to present a multi-parameter serum protein biomarker set that has predictive value prior to the start of anti-TNF treatment. Ultimately, this finding may contribute to a personalized form of medicine, whereby a specific therapy will be applied that is best suited to an individual patient.
19180516 Evaluation of the efficacy and safety of pamapimod, a p38 MAP kinase inhibitor, in a doubl 2009 Feb OBJECTIVE: To determine the efficacy and safety of pamapimod (a selective inhibitor of the alpha-isoform of p38 MAP kinase) as monotherapy in comparison with methotrexate (MTX) treatment in adult patients with active rheumatoid arthritis (RA). METHODS: Patients were randomly assigned to 1 of 4 treatment groups and received 12 weeks of double-blind treatment. One group received MTX (7.5 mg/week with planned escalation to 20 mg/week), and 3 groups received pamapimod (50, 150, or 300 mg) once daily. The primary efficacy end point was the proportion of patients meeting the American College of Rheumatology 20% improvement criteria (achieving an ACR20 response) at 12 weeks. Secondary end points included ACR50 and ACR70 responses, change from baseline in the Disease Activity Score in 28 joints (DAS28), categorical analyses of DAS28/European League Against Rheumatism response, and change from baseline in each parameter of the ACR core set of measures. Safety monitoring included recording of adverse events (AEs), laboratory testing, immunology assessments, administration of electrocardiograms, and assessment of vital signs. RESULTS: Patients assigned to receive MTX and pamapimod had similar demographics and baseline characteristics. At week 12, fewer patients taking pamapimod had an ACR20 response (23%, 18%, and 31% in the 50-, 150-, and 300-mg groups, respectively) compared with patients taking MTX (45%). Secondary efficacy end points showed a similar pattern. AEs were typically characterized as mild and included infections, skin disorders, and dizziness. Pamapimod was generally well tolerated, but the 300-mg dose appeared to be more toxic than either the 2 lower doses or MTX. CONCLUSION: The present results showed that pamapimod was not as effective as MTX in the treatment of active RA.
19290479 The investigation of synovial genomic targets of bucillamine with microarray technique. 2009 Sep OBJECTIVE: To identify the molecular mechanisms of bucillamine activity, global gene expression analysis and pathway analysis were conducted using IL-1 beta-stimulated human fibroblast-like synovial cells (FLS). METHODS: Normal human FLS were treated with IL-1 beta in the presence or absence of 10 and 100 microM bucillamine for 6 h. Total RNA was extracted and global gene expression levels were detected using a 44 k human whole genome array. Data were analyzed using Ingenuity pathway analysis. RESULTS: Numerous pathways were activated by IL-1 beta stimulation. At both concentrations, bucillamine suppressed nine signal pathways stimulated by IL-1 beta. CONCLUSIONS: Bucillamine effectively inhibited fibroblast growth factor (FGF) signaling and tight junction signaling activated by IL-1 beta in FLS. Suppression of these signal pathways may correlate with the pharmacologic mechanisms of bucillamine. In particular, the suppression of FGF signaling by bucillamine is remarkable because the activation of FGF signaling may be involved in rheumatoid arthritis pathology.
19541452 Items from patient-oriented instruments can be integrated into interval scales to operatio 2009 Sep OBJECTIVE: To exemplify the construction of interval scales for specified categories of the International Classification of Functioning, Disability and Health (ICF) by integrating items from a variety of patient-oriented instruments. STUDY DESIGN AND SETTING: Psychometric study using data from a convenience sample of 122 patients with rheumatoid arthritis. Patients completed six different patient-oriented instruments. The contents of the instrument items were linked to the ICF. Rasch analyses for ordered-response options were used to examine whether the instrument items addressing the ICF category b130: Energy and drive functions constitute a psychometrically sound interval scale. RESULTS: Nineteen items were linked to b130: Energy and drive functions. Sixteen of the 19 items fit the Rasch model according to the chi-square (chi(2)) statistic (chi(2)(df=32)=38.25, P=0.21) and the Z-fit statistic (Z(Mean)=0.451, Z(SD)=1.085 and Z(Mean)=-0.223, Z(SD)=1.132 for items and persons, respectively). The Person Separation Index r(beta) was 0.93. CONCLUSION: The ICF category interval scales to operationalize single ICF categories can be constructed. The original format of the items included in the interval scales remains unchanged. This study represents a step forward in the operationalization and future implementation of the ICF.
19821006 Decoy receptor 3 is highly expressed in patients with rheumatoid arthritis. 2010 Feb Decoy receptor 3 (DcR3), a member of the tumor necrosis factor receptor (TNFR) superfamily, is a soluble receptor that binds to the TNF family including Fas ligand (Fas-L), LIGHT, and TL1A. DcR3 is mostly expressed in tumor cells and competitively inhibits the TNF family. We previously demonstrated that overexpressed DcR3 in rheumatoid synovial cells protects the cells from apoptosis in vitro. The objective of the study was to investigate DcR3 expression in serum and joint fluids of patients with rheumatoid arthritis (RA) and osteoarthritis (OA), and to analyze the correlations with disease activities and TNFalpha expression. Sera and joint fluids were collected from patients with RA and OA. Expression of DcR3 in sera and joint fluids was measured by ELISA. The concentration of DcR3 in sera and joint fluids of RA patients was significantly higher than that in sera and joint fluids of OA patients. A correlation between serum DcR3 concentration and disease activity was not observed, but the serum DcR3 concentration was strongly correlated with the TNFalpha concentration. DcR3 was highly expressed in serum and joint fluids of RA patients.
19415375 Rheumatoid leptomeningitis: rare complication of rheumatoid arthritis. 2009 Sep Rheumatoid leptomeningitis is a rare complication of rheumatoid arthritis (RA). We describe a woman with rheumatoid leptomeningitis presenting with acute-onset behavioral changes and consciousness disturbance in the early stage of RA. On fluid-attenuated inversion recovery images or diffusion-weighted images, high-signal-intensity lesions in the subarachnoid spaces of the right frontal lobe were observed. Biopsies of brain tissues and the dura mater located in the right frontal lobe were obtained. On the basis of the findings of histopathological analysis, a diagnosis of necrotizing granulomas involving the leptomeninges consistent with rheumatoid leptomeningitis was made. An early diagnosis of rheumatoid leptomeningitis and immediate initiation of treatment may prevent neurological sequelae.
19137354 Translation and validation of the Persian version of the Arthritis Impact Measurement Scal 2009 May Cultural adaptation and validation of the Persian version of the Arthritis Measurement Scales 2-Short Form (AIMS2-SF). The translation and cultural adaptation of the original questionnaire was carried out in accordance with published guidelines. Three hundred and fifty consecutive Persian-speaking patients with rheumatoid arthritis (RA) were asked to complete the AIMS2-SF, the Short Form Health Survey (SF-36), and four visual analog scales (VAS) for pain, joint stiffness, and patient's and physician's global assessment to test convergent validity. In addition, 90 randomly selected patients were asked to complete the questionnaire 48 h later for the second time. Moderate to high correlation were found between the AIMS2-SF and subscales of the SF-36 and VAS for pain, morning stiffness, and patient's and physician's global assessment. Cronbach's alpha coefficient for the Persian AIMS2-SF scales ranged from 0.74 to 0.89. The Persian AIMS2-SF scales showed excellent test-retest reliability with Intraclass Correlation Coefficient ranging from 0.83-0.93 (p < 0.01). The results of the present study showed that the Persian AIMS2-SF has reasonably good convergent validity, internal consistency, and test-retest reliability in patients with RA. It can now be applied in clinical settings and future outcome studies in Iran.
20642867 Remission makes its way to rheumatology. 2010 Remission was a rare event, even in the most advanced rheumatology clinics, until recent times. However, in the early 1990s, it was chosen as the treatment goal and the primary outcome measure for the Finnish Rheumatoid Arthritis Combination Therapy (FIN-RACo) trial, which can be considered the beginning of remission's way to rheumatology. In addition to remission in patients with rheumatoid arthritis, remission in patients with psoriatic arthritis is now being studied, although remission criteria for psoriatic arthritis have yet to be defined. Better treatment results with more active treatment strategies and availability of biologic agents motivate rheumatologists to monitor their patients as part of usual rheumatology care.
20476861 Expression of full-length and splice forms of FoxP3 in rheumatoid arthritis. 2010 Aug OBJECTIVE: The aim of our study was to compare the presence of full-length and alternative splice forms of FoxP3 mRNA in CD4 cells from rheumatoid arthritis (RA) patients and healthy controls. METHODS: A quantitative real-time polymerase chain reaction (QRT-PCR) method was used to measure the amount of FoxP3 mRNA full-length and splice forms. CD4-positive T cells were isolated from peripheral blood from 50 RA patients by immunomagnetic separation, and the FoxP3 mRNA expression was compared with the results from 10 healthy controls. RESULTS: We observed an increased expression of full-length FoxP3 mRNA in RA patients when compared to healthy controls, as well as an increase in CD25 mRNA expression, but no corresponding increase in CTLA-4 mRNA expression. The presence of an alternative splice form of FoxP3 lacking exon 2 was confirmed in both RA patients and healthy controls, but with no significant difference in expression between the two groups. There was a positive correlation between the amount of FoxP3 mRNA and the clinical inflammation parameters C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), and a negative correlation between FoxP3 mRNA and the dose of methotrexate (MTX) given to the patients. CONCLUSION: RA patients express more full-length FoxP3 than healthy controls in peripheral blood CD4-positive cells, suggesting an increased number of regulatory T cells (Tregs). However, no concomitant increase in CTLA-4 expression was seen. We therefore propose that the Tregs are left unable to suppress the ongoing inflammation due to a deficiency in CTLA-4 needed for cell contact-dependent suppression.