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

ID PMID Title PublicationDate abstract
17978505 Expression of histamine H4 receptor in synovial cells from rheumatoid arthritic patients. 2007 Nov The last of four histamine receptors (HRs), H4 receptor (H4R), was identified in the year 2000. Since that time, the H4R has been implicated in cellular mechanisms related to immune systems, inflammatory processes, and allergic reactions. We have previously reported the expression of H4R mRNA in rheumatoid arthritic (RA) synovial cell cultures by means of the RT-PCR method. The present study demonstrates the expression of H4R at the protein level in RA synovial cell cultures. We also identified that the receptor was expressed in two specific types of cell populations, fibroblast-like and macrophage-like cells from RA synovial tissues. In the culture system, the fifth generation of fibroblast-like synoviocytes showed as strong expression of H4R as in the primary culture. The results provide pragmatic evidence for H4R as a novel target in the development of pharmacotherapeutic agents for RA treatment. Furthermore, the culture system used here will be useful for future studies concerning basic molecular mechanisms underlying the pharmacology of H4R.
16848700 Fatty acids as modulators of the immune response. 2006 Research describing fatty acids as modulators of inflammation and immune responses abounds. Many of these studies have focused on one particular group of fatty acids, omega-3. The data from animal studies have shown that these fatty acids can have powerful anti-inflammatory and immunomodulatory activities in a wide array of diseases (e.g., autoimmunity, arthritis, and infection). However, the evidence from human trials is more equivocal. In this review, a historical framework for understanding how and why fatty acids may affect the immune system is provided. Second, highlights of two recent landmark reports from the Agency for Healthcare Research and Quality are presented. These reports critically evaluate the evidence from human clinical trials of omega-3 fatty acids and rheumatoid arthritis, asthma, and a few other immune-mediated diseases. Third, the data from human clinical trials investigating the impact of various bioactive fatty acids on ex vivo and in vivo immune response are reviewed. Limitations in experimental design and immune assays commonly used are discussed. The discordance between expectation and evidence in this field has been a disappointment. Recommendations for improving both animal-based and human studies are provided.
16984661 Disease-modifying antirheumatic drugs are associated with a reduced risk for cardiovascula 2006 Rheumatoid arthritis (RA) is characterized by inflammation and an increased risk for cardiovascular disease (CVD). This study investigates possible associations between CVD and the use of conventional disease-modifying antirheumatic drugs (DMARDs) in RA. Using a case control design, 613 RA patients (5,649 patient-years) were studied, 72 with CVD and 541 without CVD. Data on RA, CVD and drug treatment were evaluated from time of RA diagnosis up to the first cardiovascular event or the end of the follow-up period. The dataset was categorized according to DMARD use: sulfasalazine (SSZ), hydroxychloroquine (HCQ) or methotrexate (MTX). Odds ratios (ORs) for CVD, corrected for age, gender, smoking and RA duration, were calculated per DMARD group. Patients who never used SSZ, HCQ or MTX were used as a reference group. MTX treatment was associated with a significant CVD risk reduction, with ORs (95% CI): 'MTX only', 0.16 (0.04 to 0.66); 'MTX and SSZ ever', 0.20 (0.08 to 0.51); and 'MTX, SSZ and HCQ ever', 0.20 (0.08 to 0.54). The risk reductions remained significant after additional correction for the presence of rheumatoid factor and erosions. After correction for hypertension, diabetes and hypercholesterolemia, 'MTX or SSZ ever' and 'MTX, SSZ and HCQ ever' showed significant CVD risk reduction. Rheumatoid factor positivity and erosions both increased CVD risk, with ORs of 2.04 (1.02 to 4.07) and 2.36 (0.92 to 6.08), respectively. MTX and, to a lesser extent, SSZ were associated with significantly lower CVD risk compared to RA patients who never used SSZ, HCQ or MTX. We hypothesize that DMARD use, in particular MTX use, results in powerful suppression of inflammation, thereby reducing the development of atherosclerosis and subsequently clinically overt CVD.
16511938 Parvovirus B19 infection in patients with rheumatoid arthritis in Taiwan. 2006 May OBJECTIVE: To investigate the role of human parvovirus B19 infection in the pathogenesis of rheumatoid arthritis (RA) in Taiwan. METHODS: Seventy-eight patients with RA and 55 unrelated controls (51 trauma and 4 osteoarthritis) were enrolled. Anti-parvovirus B19 IgG and IgM antibodies were detected in plasma of patients with RA and controls by the enzyme immunoassay method. These antibodies were also detected in the synovial fluid of 18 RA patients and 52 controls. B19 DNA was measured in the plasma of 72 patients with RA and 45 controls by nested polymerase chain reaction (PCR). It was also measured in the synovial fluid of 14 RA patients and 39 controls. Immunohistochemistry was performed to detect viral capsid protein VP1 of B19 in the synovial membrane of 7 RA patients and 32 controls. HLA-DR genotyping was performed by the sequence-specific primer PCR method. The interactions between B19 infection and HLA-DR genotype and susceptibility to RA were also analyzed. RESULTS: The prevalence of B19 infection was significantly increased in patients with RA compared with controls. The positive rates of B19 DNA in plasma and synovial fluid were significantly higher in RA patients than in controls. The odds ratio of DR4(+) B19 infection(+) was higher than that in DR4(+) B19 infection(-) or DR4(-) B19 infection(+) in comparison with DR4(-) B19 infection(-). A significant association was found between RA and DR4(+) B19 infection(+) in comparison with DR4(+) B19 infection(-). The odds ratio of DR4(+) plasma B19 DNA(+) was also higher than that of DR4(+) plasma B19 DNA(-) or DR4(-) plasma B19 DNA(+) in comparison with DR4(-) plasma B19 DNA(-). RA tended to be associated with DR4(+) plasma B19 DNA(+) compared with DR4(+) plasma B19 DNA(-). CONCLUSION: The prevalence of parvovirus B19 infection was significantly higher in patients with RA than in controls. Synergistic effects were present between HLA-DR4 and parvovirus B19 infection or plasma B19 DNA for susceptibility to RA. Parvovirus B19 infection may play a role in susceptibility to RA.
19019895 Formation of antibodies against infliximab and adalimumab strongly correlates with functio 2009 Nov BACKGROUND: Tumour necrosis factor alpha (TNFalpha) neutralising antibody constructs are increasingly being used to treat rheumatoid arthritis (RA). OBJECTIVE: To determine potential differences in clinical responses, soluble drug levels and antibody formation between patients with RA receiving infliximab and adalimumab. METHODS: 69 patients with RA fulfilling the 1987 American College of Rheumatology criteria and about to start treatment with infliximab or adalimumab, were enrolled consecutively. All patients had active disease (28-joint count Disease Activity Score >3.2). Infliximab was given intravenously at 3 mg/kg at baseline and after 2, 6 and 14 weeks. Adalimumab was administered as 40 mg biweekly subcutaneously. Concomitant drug treatment was monitored and continued at constant dosage during the study. All serum samples were tested for infliximab/adalimumab levels and anti-infliximab/anti-adalimumab antibodies. RESULTS: 35 patients received infliximab, 34 received adalimumab. At 6 months, 15 (43%), 6 (17%) and 14 (40%) of the infliximab-treated patients fulfilled the EULAR criteria for good, moderate and non-responders, respectively, whereas the corresponding figures for adalimumab-treated patients were 16 (47%), 8 (24%) and 10 (29%). Clinical responses correlated with the levels of S-infliximab/adalimumab and the formation of anti-infliximab/anti-adalimumab antibodies. CONCLUSION: The clinical response to two anti-TNFalpha biological agents closely follows the trough drug levels and the presence of antibodies directed against the drugs. Further studies that focus on the underlying pathways leading to antibody formation are warranted to predict immunogenicity of these expensive biological agents and treatment outcomes.
16508926 Predictors of joint damage in patients with early rheumatoid arthritis treated with high-d 2006 Mar OBJECTIVE: To identify disease characteristics leading to progression of joint damage in patients with early rheumatoid arthritis (RA) treated with methotrexate (MTX) versus those treated with infliximab plus MTX. METHODS: Patients who had not previously been treated with MTX with active RA were randomly assigned to receive escalating doses of MTX up to 20 mg/week plus placebo or infliximab at weeks 0, 2, and 6, and every 8 weeks thereafter through week 46. Radiographic joint damage was assessed using the modified Sharp/van der Heijde score (SHS). The relationship between disease activity measures at baseline and week 14, as well as those averaged over time, were examined in relation to the change in SHS from baseline through week 54. RESULTS: C-reactive protein (CRP) levels, erythrocyte sedimentation rate (ESR), and swollen joint count were associated with greater joint damage progression in the MTX-only group, while none of these parameters was associated with progression in the infliximab plus MTX group. Mean changes in SHS among patients in the highest CRP (> or = 3 mg/dl) and ESR (> or = 52 mm/hour) tertiles in the MTX-only group were 5.62 and 5.89, respectively, compared with 0.73 and 1.12 in the infliximab plus MTX group (P < 0.001). Patients with greater joint damage at baseline (SHS > or = 10.5) showed less progression with infliximab plus MTX compared with MTX alone (-0.39 versus 4.11; P < 0.001). Patients receiving MTX alone who had persistently active disease at week 14 showed greater radiographic progression of joint damage than those taking MTX plus infliximab. CONCLUSION: High CRP level, high ESR, or persistent disease activity was associated with greater radiographic progression in the group taking MTX alone, while little radiographic progression was seen in patients receiving both MTX and infliximab, regardless of the abnormal levels of these traditional predictors.
16308339 Methotrexate modulates the kinetics of adenosine in humans in vivo. 2006 Apr BACKGROUND: Animal studies suggest that the anti-inflammatory effect of methotrexate (MTX) is mediated by increased adenosine concentrations. OBJECTIVE: To assess the effect of MTX on the vasodilator effects of adenosine and the nucleoside uptake inhibitor, dipyridamole, in humans in vivo as a marker for changes in adenosine kinetics. METHODS: Ten patients with active arthritis were treated with MTX (15 mg/week). Measurements were performed before and after 12 weeks of treatment. At these time points, the activity of adenosine deaminase was measured in isolated lymphocytes, and forearm blood flow (FBF) was determined by venous occlusion plethysmography during administration of adenosine and dipyridamole into the brachial artery. RESULTS: The Vmax of adenosine deaminase in lymphocytes was reduced by MTX treatment (p<0.05). MTX significantly enhanced vasodilator response to adenosine (0.5 and 1.5 microg/min/dl of forearm tissue; mean (SE) FBF ratio increased from 1.2 (0.2) to 1.4 (0.2) and 2.2 (0.2) ml/dl/min, respectively, before and from 1.3 (0.1) to 1.8 (0.2) and 3.2 (0.5) ml/dl/min during MTX treatment; p<0.05). Also, dipyridamole-induced vasodilatation (30 and 100 microg/min/dl) was enhanced by MTX (FBF ratio increased from 1.2 (0.2) to 1.5 (0.3) and 1.8 (0.2), respectively, before and from 1.3 (0.1) to 1.8 (0.2) and 2.4 (0.4) during MTX treatment; p<0.05). CONCLUSIONS: MTX treatment inhibits deamination of adenosine and potentiates adenosine-induced vasodilatation. Also dipyridamole-induced vasodilatation is enhanced by MTX treatment, suggesting an increased extracellular formation of adenosine. These effects on the adenosine kinetics in humans may contribute to the therapeutic efficacy of MTX.
19062315 IRF-4-binding protein inhibits interleukin-17 and interleukin-21 production by controlling 2008 Dec 19 The T helper 17 (Th17) cell lineage is important in inflammatory and autoimmune responses, via its ability to produce interleukin-17 (IL-17) and IL-21. Given the potentially deleterious effects of Th17 cells, their generation needs to be strictly controlled. IRF-4 is a transcription factor that has recently emerged as a key regulator of Th17 cell differentiation. Here, we showed that mice deficient in a previously isolated protein, IBP (IRF-4-binding protein), rapidly developed rheumatoid arthritis-like joint disease and large-vessel vasculitis. The pathology was associated with an enhanced responsiveness of T cells to low levels of stimulation and with the inappropriate synthesis of IL-17 and IL-21. IBP sequestered IRF-4 and prevented it from targeting the transcriptional regulatory regions of the genes that encode IL-17 and IL-21. Thus, IBP appears to be important in preventing T cell-mediated autoimmunity by ensuring that the production of IL-17 and IL-21 does not occur in response to self-antigens.
17942634 Enhancement of lymphocyte migration and cytokine production by ephrinB1 system in rheumato 2008 Jan Although the etiology of early events in rheumatoid arthritis (RA) remains undefined, an anomaly in T cell homeostasis and hyperproliferation of synovial-lining cells are involved in the disease process. Since it has been reported that the ephrin/Eph receptor system plays important signaling roles in inflammation processes, we attempted to examine ephrinB molecules in T cells and synovial cells derived from RA in this study. The expression level of ephrinB1 was significantly high in synovial fibroblasts and CD3-positive exudate lymphocytes in synovial tissues derived from patients with RA compared with those in osteoarthritis (OA). Protein and mRNA levels of ephrinB1 were also higher in peripheral blood lymphocytes (PBLs) prepared from patients with RA than those from normal controls. Similar results were obtained from an animal model of human RA, collagen antibody-induced arthritis mice. Moreover, a recombinant ephrinB1/Fc fusion protein stimulated normal PBLs to exhibit enhanced migration and production of TNF-alpha. EphrinB1/Fc also activated synovial cells established from patients with RA to produce IL-6. Tyrosine phosphorylation of EphB1 was induced in these cells by ephrinB1/Fc. The CpG islands in the 5' upstream regulatory region of the ephrinB1 gene were hypomethylated in RA patients compared with those of normal donors. These results suggest that ephrinB1 and EphB1 receptors play an important role in the inflammatory states of RA, especially by affecting the population and function of T cells. Inhibition of the ephrinB/EphB system might be a novel target for the treatment of RA.
18590111 [Neutralisation of interferon gamma--a new trend in therapy of rheumatoid arthritis]. 2008 AIM: To evaluate objectively therapeutic potentialities of a novel method of biological therapy--blocking interferon gamma (IF-gamma)--by means of a comparative analysis of using antibodies to IF-g (anti-IF-gamma) and tumor necrosis factor alpha (anti-TNF-alpha) in resistant rheumatoid arthritis (RA). MATERIAL AND METHODS: A double blind trial included 55 patients with resistant RA. They received 5 intramuscular injections of anti-IF-gamma (n = 20), anti-TNF-alpha (n = 20) and placebo (15 patients). The results were assessed on the treatment day 7 and 28. RESULTS: 16 patients withdrew because of the treatment uneffectiveness (2 from the group on anti-IF-g, 3--on anti-TNF-alpha, 11--on placebo). To the treatment day 28 the patients given anticytokines achieved significant improvement of all clinical indices while placebo group had no improvement. The highest response was observed in the group on anti-IF-gamma (ACR 70). As shown by ultrasound investigation, a significant reduction of the synovial membrane thickness took place also in administration of anti-IF-gamma. Most frequent side effect of the anticytokine therapy was mild dermatitis at injection site on treatment day 8-11. CONCLUSION: Therapeutic efficacy of anti-IF-gamma was comparable with efficacy of anti- TNF-alpha and even was superior in some aspects. The block of IF-gamma holds much promise in the treatment of RA.
18193382 Acupuncture for symptom management of rheumatoid arthritis: a pilot study. 2008 May We investigated the feasibility of a future acupuncture trial in the symptom management of rheumatoid arthritis (RA). Twenty-five patients meeting the American College of Rheumatology (ACR) criteria were recruited and given 14 sessions of individualised acupuncture treatment for 6 weeks. Improvement in symptoms was assessed using ACR 20, 50 and 70; disease activity score (DAS28); tender joint count; swollen joint count; morning stiffness and health-related quality of life using the Korean Health Assessment Questionnaire and the SF-36 at baseline and after 6 weeks. Erythrocyte sedimentation rate (ESR) was also assessed. At 6 weeks, 44%, 20%, and 12% of patients achieved ACR 20, 50 and 70 responses, respectively. Acupuncture also produced statistically significant improvements in DAS28, pain and global activity, swollen joint count, health-related quality of life (SF-36) and ESR. No major acupuncture-related adverse events were reported. Acupuncture treatment as used in this pilot study was safe and well-tolerated. The use of acupuncture for symptom management in RA warrants further investigation.
17581108 Predicting response to TNF antagonists in rheumatoid arthritis: the promise of pharmacogen 2007 Despite the demonstrated efficacy of three different classes of biologic response modifiers (BRMs) for the treatment of rheumatoid arthritis (RA), there are currently no clinical predictors or biomarkers that can rationally guide physicians in the selection of BRMs for individual patients. One promising area of translational research for patients with RA is the field of pharmacogenetics. In the absence of industry-sponsored pharmacogenetic studies of BRMs, longitudinal clinical registries may represent the most promising setting for identifying genetic biomarkers. This review focuses on published pharmacogenetic studies of TNF antagonists and discusses related methodologic issues for pharmacogenetic research using clinical registries.
17896839 Rituximab: in rheumatoid arthritis. 2007 An important role for B cells in the immunopathogenesis of rheumatoid arthritis (RA) is recognized. Rituximab is a chimeric murine/human anti-CD20 monoclonal antibody that transiently depletes CD20+ B cells. A single course of rituximab (two intravenous infusions of 1,000mg given two weeks apart) with a stable dose of methotrexate significantly improved all measures of disease activity, fatigue, and health-related quality of life relative to placebo with methotrexate. This was demonstrated in the REFLEX trial, a 24-week, randomized, double-blind, double-dummy, international, phase III study in 520 patients who had active RA despite ongoing treatment with methotrexate and had experienced an inadequate response to anti-tumor necrosis factor (TNF) therapy. Patients in REFLEX (or other studies) who responded to, and required further treatment after, an initial course of rituximab continued to respond to subsequent courses of the drug. A small subgroup of patients in REFLEX continued to respond to their first course of rituximab through 48 weeks of follow-up. Long-term treatment (up to 56 weeks) with one or more courses of rituximab in REFLEX significantly inhibited joint structural damage, the first time this effect has been reported in patients with an inadequate response to TNF inhibitors. Rituximab was generally well tolerated; the majority of adverse events were related to the first infusion of the drug, were mild to moderate in severity, and were easily managed. The adverse event profile of rituximab was unchanged after repeat courses.
17611986 2756GG genotype of methionine synthase reductase gene is more prevalent in rheumatoid arth 2007 Aug OBJECTIVE: To investigate the distribution of the A2756G polymorphism of the methionine synthase reductase (MTR) gene in patients with rheumatoid arthritis (RA) treated with methotrexate (MTX) compared with a healthy control group; and to examine the relationships among the A2756G polymorphism, plasma total homocysteine (tHcy), serum folate and vitamin B12 levels, disease activity, and MTX toxicity in patients with RA. METHODS: A cross-sectional study was performed on 86 MTX-treated RA patients, consisting of a clinical interview and physical examination to determine disease activity and MTX-related adverse reactions. Genotype analysis of the MTR gene was performed. Fasting plasma tHcy, serum folate, and vitamin B12 levels were measured. Allele and genotype distributions were compared to a healthy control group. RESULTS: The frequency of the 2756GG genotype (16.3%) in the RA study group was higher than that expected in the general population (3.6%; p < 0.000001). This genotype was associated with MTX-induced accelerated rheumatoid nodulosis (MIARN). No association of disease activity variables or plasma homocysteine with MTR A2756G polymorphisms was observed. The MTR 2756GG genotype, low plasma vitamin B12 levels, and the presence of rheumatoid nodules predicted MIARN. No association of nodulosis with any other indicator of disease activity or medical treatment was found. CONCLUSION: In our population of MTX-treated RA patients the 2756GG genotype of the MTR gene was more common than expected and was associated with MIARN.
17297622 Ocular surface and intraocular inflammation are related in SS-I and rheumatoid arthritis p 2007 Jul The purpose of this study is to evaluate the intraocular inflammation at a sub clinical level, in patients suffering from Sjogren's syndrome (SS-I) and Rheumatoid Arthritis (RA), to relate it with the ocular surface status and to verify the diagnostic performance of the method. Twenty-eight patients suffering from SS-I, 31 patients suffering from RA and 31 normal subjects matched in age and gender were included in the study. A Kowa 500F laser cell flare meter was utilized to quantify the aqueous cells and flare in vivo, ocular surface inflammation was graded by conjunctival cytology and dosage of serum albumin in tears, eye dryness was scored with Tear Function Index. All data resulted significantly different in both SS-I and RA patients vs. control group and also different comparing SS-I vs. RA patients group, except for the Flare values. A blood-aqueous barrier breakdown occurs either in SS-I and RA patients; the degree of the damage is related with ocular surface inflammation and dryness. We recommend the aqueous flare be analysed in those rheumatic patients where an ocular surface inflammation has been documented.
18535030 Contribution of PTPN22 1858T, TNFRII 196R and HLA-shared epitope alleles with rheumatoid f 2008 Aug OBJECTIVES: To evaluate the predictive value of TNFRII 196R, PTPN22 1858T and HLA-shared epitope (SE) alleles, RFs and anti-citrullinated protein antibodies (ACPAs) for RA diagnosis in a cohort of patients with very early arthritis. METHODS: We followed up 284 patients who had swelling of at least two joints that had persisted for longer than 4 weeks but had been evolving for <6 months. At 2 yrs, patients were classified as having RA or non-RA rheumatic diseases according to the ACR criteria. Patients were genotyped with respect to TNFRII 196M/R and PTPN22 1858C/T polymorphisms and HLA-SE. The presence of IgA, IgG and IgM RF isotypes and ACPA was sought in sera collected at disease onset. RESULTS: HLA-SE alleles alone, concomitant presence of TNFRII 196R and PTPN22 1858T alleles, IgA, IgG and IgM RF alone and ACPA were found to be significantly associated with RA diagnosis. Using logistic regression analysis, the concomitant presence of RF and ACPA at disease onset was the best association to predict RA diagnosis. In patients (n = 34) who did not fulfil the ACR criteria for RA at inclusion but who progressed to ACR positivity, the study of the genetic risk markers did not contribute to predict RA diagnosis at 2 yrs. CONCLUSIONS: PTPN22 1858T, TNFRII 196R and HLA-SE alleles do not improve the predictive value of RF and ACPA for RA diagnosis in our cohort, and do not contribute to an earlier diagnosis in undifferentiated patients initially negative for RF and ACPA.
18020835 Clinician's comment on the management of pain in arthritis. 2007 Nov The arthritic diseases are major sources of pain or disability, although they differ in etiology and treatment approach. For diseases such as RA, inflammation is the predominant mechanism that leads to systemic complaints such as pain as well as local destruction of cartilage and bone. In contrast, OA is primarily a degenerative process and, although inflammation may occur, it differs in quality and extent from that in the systemic inflammatory arthritidies. For both conditions, psychosocial interventions have significant positive benefits, but their application involves careful consideration of a variety of factors. These factors include the following: diagnosis, disease activity, damage, disease stage, patient age and demographics, presence of comorbidities, and availability of alternative or adjunctive approaches.
18795390 A comparative study of IgG second- and third-generation anti-cyclic citrullinated peptide 2009 Feb To compare IgG anti-cyclic citrullinated peptide (CCP) enzyme-linked immunosorbent assays (ELISAs) of second (anti-CCP2) and third generations (anti-CCP3) for the diagnosis of rheumatoid arthritis (RA), an IgA CCP3 ELISA was also evaluated. Combinations of the use of the three tests were evaluated. Anti-CCP2 IgG, anti-CCP3 IgG, and anti-CCP3 IgA antibody levels were determined by ELISAs in the serum of 70 patients with rheumatoid arthritis, 34 patients with systemic lupus erythematosus (SLE), and 54 normal subjects. We evaluated the serum levels, diagnostic performance, and the use of a combination of tests for RA diagnosis. Statistical analyses include receiver operating curves (ROCs) and others. The serum levels were higher in RA patients. Sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio (LR), and negative LR were, respectively, 78.6%, 94.3%, 91.7%, 84.7%, 13.8, and 0.23 for anti- CCP2 IgG and 82.9%, 93.2%, 90.6%, 87.2%, 12.2, and 0.18 for anti-CCP3 IgG. These values were better than the same statistical tests for anti-CCP3 IgA. ROC analysis showed that anti-CCP2 IgG and anti-CCP3 IgG had good performance and similar areas. Measuring both IgG and IgA anti-CCP tests increases the specificity if both tests were positive and increases the sensitivity if either test were positive. In our population, anti-CCP2 IgG and anti-CCP3 IgG had good diagnostic performance. Anti-CCP3 IgG had 4.3% more sensitivity than the anti-CCP2 IgG test while sustaining high specificity. This and other studies suggest the development of a dual test--CCP3 IgG and IgA that may be a potential diagnostic tool.
16868816 Rapid improvement in rheumatoid arthritis patients on combination of methotrexate and infl 2007 Jun The objectives of this study was to assess, using clinical and magnetic resonance imaging (MRI) criteria, the efficacy of combination infliximab therapy in patients with active rheumatoid arthritis (RA) refractory to methotrexate (MTX) treatment and to ascertain whether the changes in MRI parameters correlate with the clinical response. Four infusions of infliximab (3 mg/kg) at weeks 0, 2, 6, and 14 were added to a stable background dose of MTX in 19 patients with active disease. Clinical parameters were assessed before each infusion and at week 14. Dynamic contrast-enhanced MRI examination of the most severely affected wrist was performed at baseline and week 14. Synovitis severity, volume of synovitis, and synovial perfusion indices were evaluated. Significant improvement in all clinical disease activity parameters was seen at week 14 with reduction in C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and DAS28. Sixty-eight percent of patients achieved ACR20. MRI disease activity parameters also significantly decreased after treatment with reduction in grading of synovitis, volume of active synovitis, and perfusion enhancement slope. Significant positive correlations were seen between the baseline volume of synovitis and the pain score (r=0.65), patient global score (r=0.68), and health assessment questionnaire (HAQ) score (r=0.46). In conclusion, addition of infliximab to methotrexate rapidly reduces inflammation in longstanding patients with RA. Assessment of enhancing synovial volume and perfusion indices on serial MRI examination was helpful in documenting the effect of treatment over this short period.
15999273 Anti-TNF-alpha antibody Infliximab and glucocorticoids reduce serum vascular endothelial g 2006 Jan To compare the effect of oral glucocorticoid (GC) therapy with the effect of intravenous anti-TNF-alpha-therapy on serum VEGF levels of patients with rheumatoid arthritis (RA). Five RA patients (5/8) who had no prior treatment with DMARDs (Disease modifying antirheumatic drugs) or GCs were administered 20 mg prednisolone daily. Three patients who failed more than one DMARD therapy received infusion with Infliximab (200 mg). VEGF-serum levels were measured by enzyme-linked immunosorbent assay before treatment,and at day 10 or 13 during prednisolone therapy, or 14 days after the first Infliximab infusion. Serum VEGF levels in therapy naive RA patients (GC group) were higher than those in pretreated patients who received Infliximab (median serum VEGF level: 1106 vs 320 pg/ml; P=0.1). Treatment with Infliximab as well as GCs significantly decreased serum VEGF levels after 10-14 days in RA patients (median serum VEGF level after treatment: GC group 559 pg/ml, Infliximab group 92 pg/ml; P=0.01 vs without treatment or preinfusion). CONCLUSIONS: Anti-TNF-alpha antibody Infliximab as well as GC are able to decrease serum VEGF levels in patients with active RA. Whether therapeutic reduction of serum VEGF levels is associated with inhibition of angiogenesis should be evaluated in future by imaging of synovial vasculature.