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ID PMID Title PublicationDate abstract
21081190 Osteoclasts in arthritis and Th17 cell development. 2011 May Bone destruction associated with rheumatoid arthritis (RA) is mainly attributed to the abnormal activation of osteoclasts, which are terminally differentiated cells of monocyte/macrophage lineage that resorb bone matrix. Studies on the immune regulation of osteoclasts in RA have promoted the new research field of "osteoimmunology", which investigates the interplay of the skeletal and immune systems at the molecular level. This interdisciplinary field is proving to be crucial to advances in the treatment of diseases associated with the bone and/or immune systems. As for the mechanisms of the bone destruction found in RA, accumulating evidence lends support to the theory that interleukin (IL)-17-producing helper T (Th17) cells induce the expression of receptor activator of nuclear factor-κB ligand (RANKL) in synovial cells, which in turn stimulates the differentiation and activation of osteoclasts together with inflammatory cytokines. Thus, inhibition of Th17 is potentially beneficial for the amelioration of the bone damage which occurs in RA. A recent study revealed that IκBζ is essential to the development of Th17 cells. These findings comprise an important advance in our understanding of the pathogenesis of RA and potentially effective therapeutic strategies.
19864143 MRI and pathological findings of rheumatoid meningitis. 2010 Jan Rheumatoid meningitis (RM) is one of the most severe complications of rheumatoid arthritis. The mortality rate of RM is relatively high and diagnosis can be difficult. We present an 80-year-old woman who was diagnosed with microscopic findings of RM after analysis of biopsy specimens taken from a brain lesion. MRI scanning revealed meningeal enhancement in the brain, and the pathological findings were those of meningeal lymphocytic infiltration, vasculitis and rheumatoid nodules. RM is a treatable disease and in this patient RM was diagnosed on the basis of biopsy findings.
19180511 Unmasking of a protective tumor necrosis factor receptor I-mediated signal in the collagen 2009 Feb OBJECTIVE: To examine the relative importance of tumor necrosis factor receptor I (TNFRI) signaling in the hematopoietic tissue compartment in the progression of collagen-induced arthritis (CIA), a model of rheumatoid arthritis (RA). METHODS: DBA/1 mice were administered a lethal radiation dose and were then rescued with bone marrow derived from either DBA/1 or TNFRI(-/-) mice. CIA was then induced, and disease progression was characterized. RESULTS: Surprisingly, mice with CIA that received TNFRI(-/-) donor marrow developed increased disease severity as compared with control mice with CIA. This could not be attributed to an increased primary response to collagen or to the contribution of a non-DBA genetic background. In mice that received TNFRI(-/-) bone marrow, histologic markers of advanced disease were evident shortly after initiation of the immune response to collagen and long before clinical evidence of disease. Serum TNFalpha was undetectable, whereas serum interleukin-12 p40 levels were increased, at the end point of the study in mice that received TNFRI(-/-) bone marrow. CONCLUSION: These data raise the intriguing possibility of the existence of an antiinflammatory, TNFRI-mediated circuit in the hematopoietic compartment. This circuit bears a resemblance to the switch in TNFalpha function that has been observed during the resolution of bacterial infections. These data suggest that TNFRI-mediated signals in the radioresistant tissues contribute to disease progression, whereas TNFRI-mediated signals in the radiosensitive tissues can contribute to protection from disease. We thus put forward the hypothesis that the degree of response to TNFalpha blockade in RA is dependent in part on the relative genetic strengths of these 2 pathways.
20424918 Association of polymorphisms in the human IL-10 and IL-18 genes with rheumatoid arthritis. 2011 Jan The decrease of anti-inflammatory cytokine and increase of pro-inflammatory cytokine was observed in rheumatoid arthritis (RA). Interleukin-10 (IL-10), a potent anti-inflammatory cytokine, has been demonstrated to suppress joint swelling and deformation in RA animal model. Interleukin-18 (IL-18), a widely distributed pro-inflammatory cytokine, induces the production of IFN-γ, activate NK cells, and promote inflammation. Recent studies demonstrated that the serum IL-10 and IL-18 levels may be influenced by genetics and related to susceptibility to several autoimmune diseases. In the present study, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing techniques, we analyzed the genotype and allele distributions of two single nucleotide polymorphisms (SNP) loci in the promoter region of IL-10 and IL-18 genes (IL-10-592 A/C and IL-18-607 A/C loci, respectively). Our results indicated that IL-10-592 allelic and genotypic frequencies were significantly different between the RA patients and normal subjects (P<0.05). In addition, significant differences of IL-10-592 allelic and genotypic frequencies were also detected between the patients with or without anti-cyclic citrullinated peptide antibody (anti-CCP) (P<0.05). In contrast, allelic and genotypic frequencies of IL-18-607 did not show significant difference between RA patients and normal subjects (P>0.05) or between anti-CCP-positive and anti-CCP-negative RA patients (P>0.05). Furthermore, ELISA detection of IL-10 and IL-18 serum levels revealed that the genotype of IL-10-592 was associated with IL-10 serum level (P<0.05), but the genotype and allele frequency of IL-18-607 was not associated with IL-18 serum level (P>0.05). Taken together, our findings provide new insight for the polymorphism of IL-10 gene in the pathogenesis of RA.
19882054 Comparison of xanthine oxidase levels in synovial fluid from patients with rheumatoid arth 2009 Nov OBJECTIVE: To search whether xanthine oxido-reductase (XOR) present in the synovium is also liberated, to determine its activity in synovial fluid and to establish a possible relationship between XOR levels in rheumatoid arthritis (RA) and non-RA patients. METHODS: This study was carried out in the Laboratory of Immunology, University Ferhat Abbas, Setif, Algeria from 2001-2008. This study is a retrospective controlled study matching cases with RA to non rheumatoid joint inflammations. Synovial fluid (SF) samples were collected with consent of the patients, at Setif University Hospital, from adults suffering from RA (n=36) or only with joint inflammations (n=52). After its detection in SF with indirect enzyme-linked immunosorbent assay (ELISA) and dot-immunobinding, using anti-bovine XOR as first antibodies, XOR was assayed with capture ELISA. RESULTS: Xanthine oxidoreductase is found in all studied SF. Capture ELISA showed levels up to 0.762 and 0.143 mg/mL in SF of RA and other joint inflammations patients, respectively. In most cases, more than 50% of synovial XOR is present as oxidase form. Positive correlation was observed between enzyme level and the disease severity since RA patients had a significantly high enzyme amount compared to patients with other less severe arthritic pathologies. CONCLUSION: These results suggest that the enzyme could well be involved in joint inflammation probably by producing reactive oxygen species.
21080925 Therapeutic potential of human umbilical cord mesenchymal stem cells in the treatment of r 2010 INTRODUCTION: Rheumatoid arthritis (RA) is a T-cell-mediated systemic autoimmune disease, characterized by synovium inflammation and articular destruction. Bone marrow mesenchymal stem cells (MSCs) could be effective in the treatment of several autoimmune diseases. However, there has been thus far no report on umbilical cord (UC)-MSCs in the treatment of RA. Here, potential immunosuppressive effects of human UC-MSCs in RA were evaluated. METHODS: The effects of UC-MSCs on the responses of fibroblast-like synoviocytes (FLSs) and T cells in RA patients were explored. The possible molecular mechanism mediating this immunosuppressive effect of UC-MSCs was explored by addition of inhibitors to indoleamine 2,3-dioxygenase (IDO), Nitric oxide (NO), prostaglandin E2 (PGE2), transforming growth factor β1 (TGF-β1) and interleukin 10 (IL-10). The therapeutic effects of systemic infusion of human UC-MSCs on collagen-induced arthritis (CIA) in a mouse model were explored. RESULTS: In vitro, UC-MSCs were capable of inhibiting proliferation of FLSs from RA patients, via IL-10, IDO and TGF-β1. Furthermore, the invasive behavior and IL-6 secretion of FLSs were also significantly suppressed. On the other hand, UC-MSCs induced hyporesponsiveness of T cells mediated by PGE2, TGF-β1 and NO and UC-MSCs could promote the expansion of CD4(+) Foxp3(+) regulatory T cells from RA patients. More importantly, systemic infusion of human UC-MSCs reduced the severity of CIA in a mouse model. Consistently, there were reduced levels of proinflammatory cytokines and chemokines (TNF-α, IL-6 and monocyte chemoattractant protein-1) and increased levels of the anti-inflammatory/regulatory cytokine (IL-10) in sera of UC-MSCs treated mice. Moreover, such treatment shifted Th1/Th2 type responses and induced Tregs in CIA. CONCLUSIONS: In conclusion, human UC-MSCs suppressed the various inflammatory effects of FLSs and T cells of RA in vitro, and attenuated the development of CIA in vivo, strongly suggesting that UC-MSCs might be a therapeutic strategy in RA. In addition, the immunosuppressive activitiy of UC-MSCs could be prolonged by the participation of Tregs.
19919943 Circulating microparticles remain associated with complement activation despite intensive 2010 Jul OBJECTIVES: Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease characterised by synovitis and joint destruction. The pathogenesis of RA is not clear, but is considered to be an immune-mediated inflammatory disorder, in which the complement system plays an important role. Although cell-derived microparticles (MPs) have been associated with inflammation and complement activation, it is unknown whether MPs are either cause or consequence. Therefore, we investigated whether circulating MPs differ between patients with very early as yet untreated arthritis and healthy controls, and whether intensive anti-inflammatory treatment of such patients affects circulating MPs. METHODS: Patients with RA (n=24) and controls (n=15) were included. Nine patients with RA were re-evaluated after 8 weeks of intensive treatment with a combination of drugs ('COmBination therapy in Rheumatoid Arthritis' (COBRA) scheme). Disease activity was measured by erythrocyte sedimentation rate (ESR), C reactive protein (CRP) and Disease Activity Score for 28 joints (DAS28). Flow cytometry was used to study MPs and exposure of complement activator molecules and complement components. RESULTS: At baseline, concentrations of MPs exposing C1q, CRP or serum amyloid-P (SAP)were all significantly elevated in patients with early RA compared to controls (p=0.003, p=0.002 and p=0.003, respectively). Upon treatment, DAS28 score, ESR and CRP levels significantly decreased (p=0.008, p=0.008 and p=0.012), but the concentrations of circulating MPs and MPs exposing complement components or activator molecules were unaffected. CONCLUSION: Circulating MPs exposing complement components or activator molecules are elevated in early RA. Since a strong anti-inflammatory therapy suppressed inflammation in patients with early RA but not levels of circulating MPs, it is unlikely that inflammation is the main underlying cause of MP release in these patients.
20646949 Rheumatoid arthritis and periodontal disease. 2010 Dec The prevalence of periodontal disease has increased two-fold among patients with rheumatoid arthritis (RA) compared to the general population. This increased prevalence is unrelated to secondary Sjögren's syndrome but instead reflects shared pathogenic mechanisms, including an increased prevalence of the shared epitope HLA-DRB1-04; exacerbated T-cell responsiveness with high tissue levels of IL-17; exaggerated B-cell responses, with plasma cells being the predominant cell type found within gingival tissue affected with periodontitis and B cells being twice as numerous as T cells; RANK overexpression; and an increase in the ratio of RANK-L over osteoprotegerin with a high level of RANK-L expression on gingival B cells, most notably those capable of recognizing Porphyromonas gingivalis. Other factors conducive to periodontitis include smoking and infection with the Epstein-Barr virus or cytomegalovirus, which act by promoting the growth of organisms such as P. gingivalis, whose DNA is often found in synovial tissue from RA patients. P. gingivalis produces the enzyme peptidylarginine deiminase that induces citrullination of various autoantigens, and levels of anti-CCP antibodies are considerably higher in RA patients with than without periodontal disease, suggesting that periodontitis may contribute to the pathogenesis of RA. Further support for this hypothesis comes from evidence that other antigens involved in RA, such as HC-gp39, are also present in gingival tissue. TNFα antagonists slow alveolar resorption but may perpetuate infection of periodontal pockets. Therefore, rheumatology patients, including those taking biotherapies, are likely to benefit from increased referral to dental care (e.g., scaling, root planing and, if needed, dental surgery), particularly as periodontitis is also associated with an increased risk of premature atheroma.
20430577 Response times follow lognormal or gamma distribution in arthritis patients. 2010 Dec OBJECTIVE: This study evaluated the statistical distribution of time to treatment response in patients with rheumatic diseases. STUDY DESIGN AND SETTING: The study used a secondary data analysis design. Data from the trial of etanercept and methotrexate with radiographic patient outcomes were used to model the response times for etanercept (ETN), methotrexate (MTX), and combined ETN+MTX in patients with rheumatoid arthritis. The German etanercept registry was used to evaluate the response time distributions in patients with juvenile idiopathic arthritis. RESULTS: For MTX, the lognormal distribution was considered to be the best model for the outcome American College of Rheumatology (ACR20), lognormal, generalized gamma, and log-logistic distributions for ACR50, and lognormal and generalized gamma for ACR70. For ETN, the lognormal model was best for ACR20, the generalized gamma for ACR50, and both lognormal and generalized gamma distributions for ACR70. For combined treatment, the best model was the log-logistic distribution for ACR20, generalized gamma for ACR50, and both lognormal and generalized gamma distributions for ACR70. For the German etanercept registry, the lognormal distribution was the best model for all three outcomes of pediatric ACR30, ACR50, and ACR70 without interval censoring. CONCLUSION: Study designs might be more efficient if the response distributions are taken into consideration during planning.
21073280 IL-19, IL-20 and IL-24: potential therapeutic targets for autoimmune diseases. 2011 Feb IL-19, IL-20 and IL-24 are members of the IL-10 family of cytokines, the human IL-19, IL-20 and IL-24 genes are all located on the q32 region of chromosome 1, and the three cytokines also share a common receptor IL-20R1/IL-20R2 heterodimer. These cytokines due to the similarity and shared receptor usage, are quite overlapping in function. Recently, the available evidence has indicated that interaction of these cytokines with their receptors might exhibit pro-inflammatory effects on autoimmune diseases, particularly psoriasis and rheumatoid arthritis. Since an imbalance between anti- and pro-inflammatory cytokines contribute to the development of autoimune diseases, these cytokines may be implicated in the pathogenesis of autoimmunity. In this paper, we concisely discuss the biological features of IL-19, IL-20 and IL-24, and focus on their potential roles in autoimmune diseases. Hopefully the information obtained will lead to a better understanding of the pathogenesis and development of novel therapeutic strategies for autoimmune diseases.
19727993 Revision total knee arthroplasty for aseptic and septic causes in patients with rheumatoid 2010 Jan Revision total knee arthroplasty in patients with rheumatoid arthritis can be challenging. We asked whether we could confirm previously reported high failure rates following revision total knee arthroplasty in patients with rheumatoid arthritis. We therefore determined the Knee Society knee score and function scores, radiographic evidence of failure, and overall survival of the revision procedure in these patients. We retrospectively reviewed 39 patients with rheumatoid arthritis who underwent 45 TKA revisions from 1994 to 2006. Twenty-seven of the 45 TKA revisions were for mechanical failure of the prosthetic components and 18 for infection. Five of the 27 knees (19%) revised for mechanical failure subsequently failed a second time. Five of the 18 patients who underwent revision for infection died within 6 months and three of the remaining knees failed secondary to reinfection. Excluding the knees that failed, the average Knee Society knee score and function score improved in both subgroups. Two knees had radiographic evidence of nonprogressive tibial radiolucencies. The probability of survival for all knees (revision as the end point) was 76% +/- 9% at 5 years. We confirmed the previously reported high mortality and subsequent failure rates following revision total knee arthroplasty for both mechanical issues and infection in patients with rheumatoid arthritis and emphasize the potential difficulties in treating these patients. LEVEL OF EVIDENCE: Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.
19472967 High revision rate after total elbow arthroplasty with a linked semiconstrained device. 2009 May The clinical results of semiconstrained total elbow arthroplasty have been encouraging, especially in rheumatoid arthritis. This article presents medium-term clinical results, revision rates, and reasons for revision of a semiconstrained linked total elbow device (Solar Total Elbow; Stryker, Mahwah, New Jersey). We retrospectively reviewed 17 consecutive total elbow arthroplasty patients operated on between February 1994 and March 2001. Thirteen patients were available for clinical evaluation with an average follow-up of 8.4 years (range, 4-12.6 years). The presenting diagnosis was posttraumatic arthritis in 6 patients, rheumatoid arthritis in 6, and gouty arthritis in 1, with an average patient age of 63.4 years. The results were analyzed with regard to complications following the procedure, functional outcome using the Mayo Elbow Performance Score (MEPS), and radiological evaluation at latest follow-up. The mean MEPS improved from 32.1 to 65 at latest follow-up. Three patients had excellent results, 5 had good results, 1 had a fair result, and 4 had poor results. Seven patients required at least 1 revision surgery, including 2 with humeral component loosening, 2 with ulnar component loosening, and 2 with bushing failure. One patient required resection arthroplasty for deep periprosthetic infection. Three patients eventually sustained periprosthetic fractures. Five patients with rheumatoid arthritis and 2 patients with posttraumatic arthritis underwent revision surgery. Poor clinical outcomes and a high revision rate were noted in patients with posttraumatic arthritis. Further comparative studies with other semiconstrained devices are necessary to determine their clinical effectiveness in patients with rheumatoid arthritis.
19604347 Mesenteric rheumatoid nodules masquerading as an intra-abdominal malignancy: a case report 2009 Jul 15 BACKGROUND: Rheumatoid nodules are the most common extra-articular findings in patients with rheumatoid arthritis. They occur most commonly at pressure points such as the extensor surfaces of the forearms, fingers, and occiput, but have also been reported to occur in unusual locations including the central nervous system, pericardium, pleura, and sclera. We present the unusual case of rheumatoid nodules in the small bowel mesentery masquerading as an intra-abdominal malignancy. CASE PRESENTATION: A 65-year-old-male with a known history of longstanding erosive, nodular, seropositive rheumatoid arthritis was incidentally found to have a mesenteric mass on computed tomography (CT) exam of the abdomen. This mass had not been present on prior imaging studies and was worrisome for a malignancy. Attempts at noninvasive biopsy were nondiagnostic but consistent with a "spindle" cell neoplasm. Laparotomy revealed extensive thickening and fibrosis of the small bowel mesentery along with large, firm nodules throughout the mesentery. A limited bowel resection including a large, partially obstructing, nodule was performed. Pathology was consistent with an unusual presentation of rheumatoid nodules in the mesentery of the small bowel. CONCLUSION: Rheumatoid nodules should be considered in the differential diagnosis of a patient who presents with an intra-abdominal mass and a history of rheumatoid arthritis. Currently, no tests or imaging modality can discriminate with sufficient accuracy to rule out a malignancy in this difficult diagnostic delimma. Hopefully, this case will serve as impetus for further study and biomarker discovery to allow for improved diagnostic power.
20454862 The relationship between change in subjective outcome and change in disease: a potential p 2010 Sep BACKGROUND: Response shift theory suggests that improvements in health lead patients to change their internal standards and re-assess former health states as worse than initially rated when using retrospective ratings via the then-test. The predictions of response shift theory can be illustrated using prospect theory, whereby a change in current health causes a change in reference frame. Therefore, if health deteriorates, the former health state will receive a better rating, whereas if it improves, the former health state will receive a worse rating. OBJECTIVE: To explore the predictions of response shift and prospect theory by relating subjective change to objective change. METHODS: Baseline and 3-month follow-up data from a cohort of rheumatoid arthritis patients (N = 197) starting on TNFalpha-blocking agents were used. Objective disease change was classified according to a disease-specific clinical outcome measure (DAS28). Visual analogue scales (VAS) for general health (GH) and pain were used as self-reported measures. Three months after starting on anti-TNFalpha, patients used the then-test to re-rate their baseline health with regard to general health and pain. Differences between then-test value and baseline values were calculated and tested between improved, non-improved and deteriorated patients by the Student t-test. RESULTS: At 3 months, 51 (25.9%) patients had good improvement in health, 83 (42.1%) had moderate improvement, and 63 (32.0%) had no improvement or deteriorated in health. All patients no matter whether they improved, did not improve, or even became worse rated their health as worse retrospectively. The difference between the then-test rating and the baseline value was similarly sized in all groups. CONCLUSION: More positive ratings of retrospective health are independent of disease change. This suggests that patients do not necessarily change their standards in line with their disease change, and therefore it is inappropriate to use the then-test to correct for such a change. If a then-test is used to correct for shifts in internal standards, it might lead to the paradoxical result that patients who do not improve or even deteriorate increase significantly on self-reported health and pain. An alternative explanation for differences in retrospective and prospective ratings of health is the implicit theory of change which is more successful in explaining our results than prospect theory.
20980704 Fcγ receptor IIIb polymorphism and use of glucocorticoids at baseline are associated with 2011 Feb OBJECTIVE: Infusion reaction is a major adverse event in patients with rheumatoid arthritis (RA) treated with infliximab. The possible factors including Fcγ receptor (FcγR) polymorphism associated with the development of infusion reactions in patients with RA receiving infliximab were prospectively examined. METHODS: 96 patients with RA were enrolled and scheduled to receive infliximab at a dose of 3 mg/kg at weeks 0, 2 and 6 and every 8 weeks thereafter. Genetic polymorphisms for FcγR were examined in FCGR3A 176F/V and FCGR3B NA1/2 alleles by allele-specific PCR analysis. RESULTS: An infusion reaction was observed in 17 patients (18%) during 52 weeks of treatment with infliximab. The FCGR3B NA1/NA1 genotype was found in 75% of the patients with infusion reactions and in only 37% of those without (p=0.01), whereas the FCGR3A 176F/V genotype was equally distributed in the patients with or without infusion reactions. Glucocorticoids were used in 53% of the patients who developed an infusion reaction and in 80% of those without an infusion reaction (p=0.02). A multivariable logistic regression model showed that the FCGR3B NA1/NA1 genotype and use of glucocorticoids at baseline could be used as independent predictive factors for infusion reactions (OR 6.1 (95% CI 1.9 to 24.3) and OR 0.26 (95% CI 0.08 to 0.84), respectively). The presence of anti-infliximab antibody during infliximab treatment was also associated with infusion reactions. CONCLUSION: FCGR3B NA1/NA1 genotype, use of glucocorticoids and the presence of anti-infliximab antibody accounted for nearly all patients with RA who developed infusion reactions.
19797509 Pulmonary nodulosis and aseptic granulomatous lung disease occurring in patients with rheu 2009 Nov OBJECTIVE: To describe cases of development of pulmonary nodulosis or aseptic granulomatous lung disease in patients with rheumatoid arthritis (RA) receiving anti-tumor necrosis factor-alpha (TNF-alpha) therapy. METHODS: A call for observation of such cases was sent to members of the French "Club Rhumatismes et Inflammation." The cases had to occur after introduction of TNF-alpha-blocking therapy. RESULTS: Eleven cases were examined: 6 patients were treated with etanercept, 2 with infliximab, and 3 with adalimumab. Pulmonary nodular lesions were observed after a mean treatment period of 23.3 +/- 15.3 months. Clinical symptoms were observed in 5 cases. Radiographs or computed tomography of the chest showed single or multiple nodular lesions in 10 cases and hilar adenopathies in 1 case. Biopsy of the nodular chest lesions or mediastinal lymphadenopathies were performed in 8 patients, and revealed typical rheumatoid nodules in 4 cases and noncaseating granulomatous lesions in 4 cases. Mycobacterial or opportunistic infections were excluded for all cases. Outcome was favorable for all the patients, with either discontinuation or maintenance of anti-TNF-alpha treatment. CONCLUSION: Aseptic pulmonary nodular inflammation corresponding to rheumatoid nodules or noncaseating granulomatous inflammation can occur during anti-TNF-alpha therapy for RA, mainly etanercept. The mechanism explaining such a reaction is not clear but certainly includes different processes. These cases of pulmonary nodular inflammation generally have a benign course and do not systematically require withdrawal of treatment.
19741011 Evaluation of two strategies (initial methotrexate monotherapy vs its combination with ada 2009 Nov OBJECTIVES: In early and active RA despite MTX, continuous treatment with TNF blockers in combination with MTX is recommended. To compare this strategy with an initial combination of MTX and adalimumab (ADA) given for 3 months and then adjusted based on the disease activity status. METHODS: Prospective unblinded randomized multicentre controlled 1-year trial in which 65 patients with early (<6 months) and active [disease activity score (DAS28(ESR)) >5.1] RA were assigned to Group 1 (32 patients): MTX (0.3 mg/kg/week, maximum of 20 mg/week, without escalating dose regimen) or to Group 2 (33 patients): initial combination therapy with MTX (as in Group 1) and ADA (40 mg eow). In both groups, treatment was adjusted every 3 months. The aim was to achieve a low DAS (DAS28(ESR) <3.2). RESULTS: From Week 12 until Week 52, seven patients in Group 1 and 11 patients in Group 2 remained in low disease activity state while receiving MTX monotherapy (P = 0.28). The 1-year area under the curve (AUC) of DAS28 was lower in Group 2 owing to an initial better response. The total intake of anti-TNF-alpha and the mean increase in total modified Sharp score was similar in the two groups. CONCLUSIONS: Initial combination of MTX and ADA and then an adjusted based on the disease activity status achieved a faster control of disease activity but did not increase the number of patients for whom anti-TNF-alpha treatment was not needed after 12 weeks nor a better subsequent clinical or radiological outcome than a 3-month delayed initiation of anti-TNF in patients with still active disease despite MTX.
19643412 Atherogenic lipoprotein phenotype and LDL size and subclasses in drug-naïve patients with 2009 Dec OBJECTIVE: Subjects with rheumatoid arthritis (RA) have increased cardiovascular risk and may show atherogenic forms of dyslipidemia. The present study investigated whether patients with early RA, beyond alterations in plasma lipids, also show lower LDL size and altered LDL subclass distribution. DESIGN AND METHODS: We identified 25 subjects with RA (47+/-8 years, body mass index (BMI) 25+/-4kg/m(2)) by the American College of Rheumatology diagnostic criteria, with a disease durations <1 year and no prior treatment against it. In patients and 22 healthy subjects matched for age and BMI (controls) we measured plasma lipids and LDL size and subclasses by gradient gel electrophoresis. RESULTS: As compared to controls RA patients had higher plasma triglycerides (1.8+/-0.5 vs. 1.0+/-0.5mmol/L, p<0.0001) and lower HDL-cholesterol concentrations (1.2+/-0.2 vs. 1.4+/-0.2mmol/L, p=0.0027), while total- and LDL-cholesterol concentrations were similar. LDL particle size was lower in RA patients than controls (264+/-7 vs. 281+/-9A, p<0.0001), due to less LDL-I (31+/-6 vs. 38+/-7%, p=0.0004) and LDL-IIA (14+/-3 vs. 16+/-3%, p=0.0182), and more LDL-IIIB (7+/-1 vs. 5+/-1%), -IVA (11+/-2 vs. 8+/-2%) and -IVB particles (12+/-2 vs. 9+/-2%,) (p<0.0001 for all). Further, about 1/3 of patients showed the complete "atherogenic-lipoprotein-phenotype" (e.g. the concomitant presence of high triglycerides, low HDL-cholesterol and elevated small, dense LDL). CONCLUSIONS: Beyond plasma lipids, increased levels of small, dense LDL seems to be common in drug-naïve patients with early RA. Yet, whether these findings affect the atherogenic process and the clinical endpoints in these subjects remains to be determined by future prospective studies.
18979150 Study of active controlled tocilizumab monotherapy for rheumatoid arthritis patients with 2009 We investigated the clinical efficacy and safety of tocilizumab (a humanized anti-IL-6 receptor antibody) monotherapy in active rheumatoid arthritis (RA) patients with an inadequate response to low dose methotrexate (MTX). In a multicenter, double-blind, randomized, controlled trial, 125 patients were allocated to receive either tocilizumab 8 mg/kg every 4 weeks plus MTX placebo (tocilizumab group) or tocilizumab placebo plus MTX 8 mg/week (control group) for 24 weeks. The clinical responses were measured using the American College of Rheumatology (ACR) criteria and the Disease Activity Score in 28 joints. Serum vascular endothelial growth factor (VEGF) levels were also monitored. At week 24, 25.0% in the control group and 80.3% in the tocilizumab group achieved ACR20 response. The tocilizumab group showed superior ACR response criteria over control at all time points. Additionally, serum VEGF levels were significantly decreased by tocilizumab treatment. The overall incidences of adverse events (AEs) were 72 and 92% (serious AEs: 4.7 and 6.6%; serious infections: 1.6 and 3.3%) in the control and the tocilizumab groups, respectively. All serious adverse events improved by adequate treatment. Tocilizumab monotherapy was well tolerated and provided an excellent clinical benefit in active RA patients with an inadequate response to low dose MTX.
20441874 Highly sensitive immunoassay based on E. coli with autodisplayed Z-domain. 2010 May 14 The Z-domain of protein A has been known to bind specifically to the F(c) region of antibodies (IgGs). In this work, the Z-domain of protein A was expressed on the outer membrane of Escherichia coli by using "Autodisplay" technology as a fusion protein of autotransport domain. The E. coli with autodisplayed Z-domain was applied to the sandwich-type immunoassay as a solid-support of detection-antibodies against a target analyte. For the feasibility demonstration of the E. coli based immunoassay, C-reactive protein (CRP) assay was carried out by using E. coli with autodisplayed Z-domain. The limit of detection (LOD) and binding capacity of the E. coli based immunoassay were estimated to be far more sensitive than the conventional ELISA. Such a far higher sensitivity of E. coli based immunoassay than conventional ELISA was explained by the orientation control of immobilized antibodies and the mobility of E. coli in assay matrix. From the test results of 45 rheumatoid arthritis (RA) patients' serum and 15 healthy samples, a cut-off value was established to have optimal sensitivity and selectivity values for RA. The CRP test result of each individual sample was compared with ELISA which is the reference method for RA diagnosis. From this work, the E. coli with Z-domain was proved to be feasible for the medical diagnosis based on sandwich-type immunoassay.