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ID PMID Title PublicationDate abstract
23942828 German guidelines for the sequential medical treatment of rheumatoid arthritis with tradit 2014 Jan The German Society of Rheumatology approved new German guidelines for the sequential medical treatment of rheumatoid arthritis (RA) based on the European League Against Rheumatism (EULAR) recommendations for the management of RA published in 2010. An update of the EULAR systematic literature research was performed in Medline, Embase, and Cochrane databases. Meta-analyses, controlled trials, cohort studies, and registry data addressing traditional and biologic disease-modifying antirheumatic drugs, glucocorticoids, and treatment strategies published between January 2009 and August 2011 were included. Two reviewers independently evaluated and compared the additional data that had been published after the time limit set by the EULAR recommendations. A national guideline working group developed an adapted set of recommendations. The new German guidelines were accepted by vote using an informal Delphi approach. Twelve recommendations and the resulting updated treatment algorithm were developed and approved as a practical orientation for rheumatologists. These recommendations are based on a successive treatment with traditional and biologic disease-modifying drugs depending on the individual progress of the disease and distinct patient characteristics. The German guidelines have been developed on the basis of the internationally well-recognized EULAR recommendations. In addition, more recent evidence from a systematic literature research was considered. They have been developed and approved by a group of national experts aiming at guidance for rheumatologists to reach best medical practice.
24417833 Comparison of patient reported outcomes after Triathlon(®) and Kinemax Plus prostheses. 2014 Jan INTRODUCTION: The Triathlon(®) (Stryker, Kalamazoo, MI, US) total knee replacement was designed to improve patient function and survivorship. The aim of this study was to determine whether the Triathlon(®) prosthesis produces better patient reported outcomes than a previous design by the same manufacturer, the Kinemax Plus. METHODS: The outcome of 233 knees of patients with a mean age of 68 years (range: 40-80 years) who received the Kinemax Plus prosthesis were compared with the outcomes of 220 knees of patients with a mean age of 70 years (range: 42-90 years) who received the Triathlon(®) prosthesis. Data were collected via postal questionnaire prior to surgery as well as at 8-12 weeks and at 1 year following surgery. Validated questionnaires were used including the WOMAC(®) (Western Ontario and McMaster Universities) pain and function scales, the Knee injury and Osteoarthritis Outcome Score quality of life scale and the self-administered patient satisfaction scale. RESULTS: This study found that patients who had the Triathlon(®) prosthesis had significantly better pain relief (p<0.0001), function (p=0.028), knee related quality of life (p<0.0001) and satisfaction (p=0.0003) at three months after surgery than those who received the Kinemax Plus prosthesis. In addition, knee related quality of life (p=0.002) and satisfaction (p=0.021) were significantly higher at one year after surgery in Triathlon(®) CONCLUSIONS: The findings suggest that return to function and reduction in pain may occur more quickly in patients with a Triathlon(®) prosthesis than in those with the Kinemax Plus.
23101665 Altered sequence of the ETS1 transcription factor may predispose to rheumatoid arthritis s 2013 OBJECTIVE: ETS1 belongs to the ETS family of transcription factors that regulate the expression of various immune-related genes. The aim of this study was to identify whether the ETS1 single nucleotide polymorphism (SNP) rs11221332, described in Caucasian subjects, plays a role in rheumatoid arthritis (RA) susceptibility. METHODS: We genotyped this polymorphism in 136 unrelated patients with RA and 147 healthy individuals with no history of autoimmune disease. Genotyping was performed with a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay and the data were analysed using SPSS statistical software. RESULTS: A statistically significant difference was observed in the distribution of the rs11221332 genotypes between RA patients and controls (p = 0.041). Comparing the distribution of rs11221332 alleles between the groups studied, a greater difference was found [odds ratio (OR) 1.504, 95% confidence interval (CI) 1.036-2.183; p = 0.039]. CONCLUSIONS: The present study revealed, for first time, the positive association of a polymorphism in the sequence of the ETS1 transcription factor with RA susceptibility. Further studies in other ethnic groups of patients are needed to confirm the results of the present genetic association study related to ETS1, a widely used transcription factor in the regulation of the expression of various genes.
25510954 TNFα polymorphism as marker of immunosenescence for rheumatoid arthritis patients. 2015 Jan BACKGROUND: Expansion of CD4(+)CD28(null), a common feature of immunosenescence, which has been reported in rheumatoid arthritis (RA) patients, may also be associated with a CD4(+) imbalance. Although the increase of CD4(+)CD28(null) cells has been related to TNFα exposure, nothing is known about the possible role of genetic variants of this cytokine. METHODS: Participants were genotyped for TNFA rs1800629 (-308 G>A) and frequency of the CD4(+)CD28(null), regulatory T cells and Th1 cells subsets were quantified in peripheral blood samples by flow cytometry in 129 RA patients and 33 healthy controls. RESULTS: The expansion of CD4(+)CD28(null) cells in RA patients was associated with TNFA genotype, even at diagnosis, and linked to markers of aggressive disease in patient carriers of the minor allele. Analysis of regulatory T cells and IFNγ-CD4(+) expression suggested that defective suppression and/or Th1-shift could underlie the expansion of this population in these patients. Finally, although treatment with TNFα-blockers reduced CD4(+)CD28(null) cells in most patients, only those carriers of the common GG genotype reached values within the range of HC and showed a disease activity improvement correlated to this decrease. CONCLUSIONS: Our results provide evidence for a genetic basis of the premature immunosenescence of RA patients and highlight its potential role in clinical outcome after TNFα blockade.
24996488 The "dirty little secret" exposed in the 2013 EULAR recommendations for rheumatoid arthrit 2014 Jul 1 The European League Against Rheumatism (EULAR) recently updated its recommendations on the management of rheumatoid arthritis (RA) with synthetic and disease-modifying antirheumatic drugs (DMARDs), motivated by the availability of new treatment options over the past 3 or 4 years. Modifications since 2010 include the removal of the recommendation of the use of azathioprine, cyclosporine A, or cyclophosphamide for the treatment of RA. Furthermore, there is no longer an expressed preference for tumor necrosis factor inhibitors, including the approved biosimilar tumor necrosis factor inhibitors, over abatacept (a co-stimulatory blocker), tocilizumab (an interleukin-6 inhibitor), or rituximab (a B-cell antibody) when conventional DMARDs are not sufficiently effective. However, the use of tofacitinib (a Janus-associated kinase inhibitor) should come after initial biologic treatment has failed, due to uncertainty about the long-term safety and cost considerations of tofacitinib in comparison to biologic DMARDs. It was recommended that DMARD-naive patients be treated with either conventional DMARD monotherapy or DMARD combination therapy up front, and that low-dose glucocorticoids "should be considered" as a part of the initial treatment strategy, with glucocorticoids tapered within 6 months. Because glucocorticoids have been reported to retard joint damage and have been associated with negligible adverse events at low doses, perhaps the 2013 EULAR recommendation did not go far enough in its support of low-dose glucocorticoid use. Almost 60 years have passed since the initial discovery of glucocorticoid efficacy in the treatment of RA, and despite the flurry of new and exciting medications for the treatment of RA, we still have not come to a consensus on how the first effective, and now the least expensive, RA therapy should be used.
25627219 [The prevalence of anemia in rheumatoid arthritis]. 2014 Jul OBJECTIVES: The aim of this study was to evaluate the prevalence of anaemia in rheumatoid arthritis (RA). PATIENTS AND METHODS: 89 patients who fulfilled American College of Rheumatology (ACR) criteria for RA were included in this study. The mean disease duration was 10.9±8.8 years. All patients received methotrexate (10.5±5.5 mg/week) in combination with folic acid. Steroid hormones were prescribed to 92% (19.3±3.8 mg/day) of patients. Erythrocyte sedimentation rate (ESR) and levels of hemoglobin, C-reactive protein (CRP), tumour necrosis factor-alpha (TNFα) and interleukin-1 beta (IL-1β) were evaluated in all patients. The World Health Organization (WHO) criteria for anaemia uses a hemoglobin threshold of <120 g/L for women and <130 g/L for men. RESULTS: Anaemia was observed in 57 (64%) of the patients (1st group), the other patients (2nd group) had normal levels of hemoglobin (135.5±10.7 g/L). Duration and activity of RA were significantly higher (p<0.05) in the 1st group compared with the 2nd. ESR, CRP, TNFα, and IL-1β mean levels were significantly increased (p<0.05) in the 1st group when compared with the 2nd group. Negative correlations between hemoglobin level and ESR, CRP, TNFα, and IL-1β concentrations were observed. CONCLUSION: This study showed for the first time in Ukraine that in 46% of patients with RA, anaemia was diagnosed. A reduction of hemoglobin level was associated with a high activity of disease.
24372294 Hand ultrasound: comparative study between "no rhupus" lupus erythematosus and rheumatoid 2014 Jul OBJECTIVE: To compare hand US between systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) patients. METHODS: Hands (1st-5th metacarpophalangeal [MCP] and 1st-5th proximal interphalangeal [PIP] joints) and wrists (radiocarpal and distal radioulnar joints) of 62 "no rhupus" SLE and 60 RA patients were compared through US (linear probe, 6-18 MHz). The findings were compared to clinical, functional, serological outcomes, and disease activity indices. RESULTS: 2108 and 2040 joint recesses were evaluated in SLE and AR patients, respectively. Synovitis was found in 46.8% and 75% of wrists, 83.9% and 86.7% of MCPs and 58.1% and 70% of PIPs in the SLE and RA groups, respectively. More significant US findings were found in RA group. Greater values of synovitis (mm) in RA group were only found in the joint recesses of wrist (p < 0.001-0.002). In SLE group, US findings were associated with "puffy hands," Health Assessment Questionnaire score and dynamometry. Twenty-two SLE patients (35.5%) had erosion in any of joints studied. SLE patient subgroup with US erosion was associated with hematological involvement and Jaccoud's arthropathy. CONCLUSIONS: US of "no rhupus" SLE and RA patients is different, especially in wrists. In SLE patients the clinical variable most associated with US findings was "puffy hands."
25450406 Arthritogenic T cells in autoimmune arthritis. 2015 Jan Autoimmune diseases, including arthritis, often result from an imbalance between regulatory T (Treg) cells and IL-17-producing (Th17) cells. Dozens of studies in mice and humans have shed light on the pathological significance of T cells in RA. Since Th17 cells play an important role in the exacerbation of inflammation and bone destruction in joints, it has been an important issue how arthritic Th17 cells arise. Th17 cells are generated in the local inflammatory milieu via cytokines produced by macrophages or synovial fibroblasts, while it is reported that Th17 cells are generated in the gut in the presence of specific commensal bacteria. A recent report showed a pathogenic Th17 cell subset with a distinct pattern of gene expression and a potent osteoclastogenic ability are converted from Foxp3(+) T cells in arthritic joints. Since Foxp3(+) Treg cells contain T cells which recognize self-antigens, the fate of plastic Foxp3(+) T cells can be a critical determinant of autoimmunity or self-tolerance. Further analysis on the molecular basis and antigen-specificity of arthritogenic Th17 cell subsets will be helpful to establish novel therapeutic approaches and clarify how self-tolerance breaks down in autoimmune arthritis.
23331665 Quantification of small joint space width, periarticular bone microstructure and erosions 2013 Mar OBJECTIVES: This paper aims to investigate the ability of a novel imaging technique, high-resolution peripheral quantitative computed tomography (HR-pQCT), to quantify joint space width at the metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints, and provide periarticular bone microstructure measurements (including volumetric density and morphometric indices). We also compared the sensitivity and specificity of HR-pQCT to detect erosions relative to plain radiography. METHODS: HR-pQCT imaging of the MCP and PIP joints of the dominant hand was performed in 30 rheumatoid arthritis (RA) and control subjects matched for age, sex and dominant hand use. The joint space width was calculated by determining the number of voxels between three-dimensional images of the articular surfaces. Periarticular bone microstructure was quantified for the 2nd and 3rd MCP joints using standard analysis. The presence of erosions was confirmed by viewing both two- and three-dimensional images of the joints. RESULTS: Quantitative measures of joint space width and periarticular bone microstructure were obtained with precision. Although not powered to detect differences between RA and control subjects, we identified a trend to narrowing of the 2nd MCP joints in RA (mean difference 250 μm, p=0.057). RA erosions most frequently occurred at the metacarpal head of the MCP joint, and HR-pQCT identified erosions in 24.7% more joints compared to plain radiography. CONCLUSIONS: This is the first study to exploit the quantitative capabilities of HR-pQCT to provide joint space width measurements at the MCP and PIP joints. We provide further proof that HR-pQCT improves erosion detection and yields reproducible periarticular bone microstructure measurements.
24058910 Serum proteome analysis in patients with rheumatoid arthritis receiving therapy with tocil 2013 Rheumatoid arthritis (RA) is a chronic inflammatory disorder of the synovial membrane that results in the destruction of bone and cartilage in affected joints. Tocilizumab is a biological agent and an anti-interleukin-6 (IL-6) receptor monoclonal antibody that blocks IL-6-mediated inflammatory processes in RA patients. In order to identify novel disease-related proteins and candidate biomarkers, we analyzed the changes in the serum proteome profiles of patients with RA who were treated with tocilizumab. Serum samples were collected from the RA patients before and after tocilizumab treatment. Following immunodepletion of major proteins, the proteins were digested and labeled with isobaric tag, iTRAQ reagent. The proteins were identified and quantified using liquid chromatography-tandem mass spectrometry. Among a total of 311 proteins identified, seven were decreased and 16 were increased by tocilizumab treatment. Although some of the proteins are known to be related to RA, several are currently unknown with respect to their relationship to RA and may be involved in the development of this disease. This study is the first to perform a comparative serum proteomic analysis of RA patients treated with tocilizumab. Our results may contribute to the identification of novel disease-related proteins and enhance the understanding of the pathogenesis of RA.
25156017 Boron neutron capture synovectomy (BNCS) as a potential therapy for rheumatoid arthritis: 2014 Nov Boron neutron capture synovectomy (BNCS) is explored for the treatment of rheumatoid arthritis (RA). The aim of the present study was to perform boron biodistribution studies in a model of antigen-induced arthritis (AIA) in female New Zealand rabbits, with the boron carriers boronophenylalanine (BPA) and sodium decahydrodecaborate (GB-10) to assess the potential feasibility of BNCS for RA. Rabbits in chronic phase of AIA were used for biodistribution studies employing the following protocols: intra-articular (ia) (a) BPA-f 0.14 M (0.7 mg (10)B), (b) GB-10 (5 mg (10)B), (c) GB-10 (50 mg (10)B) and intravenous (iv), (d) BPA-f 0.14 M (15.5 mg (10)B/kg), (e) GB-10 (50 mg (10)B/kg), and (f) BPA-f (15.5 mg (10)B/kg) + GB-10 (50 mg (10)B/kg). At different post-administration times (13-85 min for ia and 3 h for iv), samples of blood, pathological synovium (target tissue), cartilage, tendon, muscle, and skin were taken for boron measurement by inductively coupled plasma mass spectrometry. The intra-articular administration protocols at <40 min post-administration both for BPA-f and GB-10, and intravenous administration protocols for GB-10 and [GB-10 + BPA-f] exhibited therapeutically useful boron concentrations (>20 ppm) in the pathological synovium. Dosimetric estimations suggest that BNCS would be able to achieve a therapeutically useful dose in pathological synovium without exceeding the radiotolerance of normal tissues in the treatment volume, employing boron carriers approved for use in humans. Radiobiological in vivo studies will be necessary to determine the actual therapeutic efficacy of BNCS to treat RA in an experimental model.
23459843 Which patients are most likely to benefit from total joint arthroplasty? 2013 May OBJECTIVE: To evaluate patient predictors of good outcome following total joint arthroplasty (TJA). METHODS: A population cohort with hip/knee arthritis (osteoarthritis [OA] or inflammatory arthritis) ages ≥55 years was recruited between 1996 and 1998 (baseline) and assessed annually for demographics, troublesome joints, health status, and overall hip/knee arthritis severity using the Western Ontario and McMaster Universities OA Index (WOMAC). Survey data were linked with administrative databases to identify primary TJAs. Good outcome was defined as an improvement in WOMAC summary score greater than or equal to the minimal important difference (MID; 0.5 SD of the mean change). Logistic regression and Akaike's information criterion were used to determine the optimal number of predictors and the best model of that size. Log Poisson regression was used to determine the relative risk (RR) for a good outcome. RESULTS: Primary TJA was performed in 202 patients (mean age 71.0 years; 79.7% female; 82.7% with >1 troublesome hip/knee; 65.8% knee replacements). Mean improvement in WOMAC summary score was 10.2 points (SD 18.05; MID 9 points). Of these patients, 53.5% experienced a good outcome. Four predictors were optimal. The best 4-variable model included pre-TJA WOMAC, comorbidity, number of troublesome hips/knees, and arthritis type (C statistic 0.80). The probability of a good outcome was greater with worse (higher) pre-TJA WOMAC summary scores (adjusted RR 1.32 per 10-point increase; P < 0.0001), fewer troublesome hips/knees (adjusted RR 0.82 per joint; P = 0.002), OA (adjusted RR for rheumatoid arthritis versus OA 0.33; P = 0.009), and fewer comorbidities (adjusted RR per condition 0.88; P = 0.01). CONCLUSION: In an OA cohort with a high prevalence of multiple troublesome joints and comorbidity, only half achieved a good TJA outcome, defined as improved pain and disability. A more comprehensive assessment of the benefits and risks of TJA is warranted.
24319104 Ultrasonographic examination of rheumatoid arthritis patients who are free of physical syn 2014 Mar OBJECTIVE: The aim of this study was to investigate the characteristics of power Doppler (PD) subclinical synovitis in patients with RA who achieve clinical remission free from physical synovitis. METHODS: Twenty-nine RA patients were consecutively enrolled. All of the patients had achieved clinical remission [simplified disease activity index (SDAI) 3.3] for at least 6 months at the musculoskeletal ultrasound (MSKUS) examination. Additionally, none of the patients exhibited tender joints at 68 sites or swollen joints at 66 sites. MSKUS of bilateral wrist and finger joints, including the first to fifth MCP joints, the first IP joint and the second to fifth PIP joints, was performed and the findings obtained by grey scale (GS) and PD were graded on a semi-quantitative scale from 0 to 3. RESULTS: The median disease duration upon the introduction of DMARDs was 3 months and that at MSKUS examination was 21 months. The percentages of patients with PD synovitis in at least one joint were PD grade 1, 58.6%; PD grade 2, 31.0% and PD grade 3, 6.9%. The use of biological agents was low in patients with PD synovitis grade 2 (P < 0.05). The presence of US bone erosion was high by patient (P < 0.05) and by joint (P < 0.0001) with PD synovitis as compared with those without PD synovitis. However, no correlations were found between PD synovitis measures and serum biomarkers, including angiogenesis factors. CONCLUSION: PD subclinical synovitis correlates with several clinical characteristics, whereas conventional serum biomarkers are not useful for indicating the presence of subclinical PD synovitis.
25207845 Are sample sizes of randomized clinical trials in rheumatoid arthritis too large? 2014 Nov OBJECTIVE: We had the impression that randomized clinical trials (RCTs) frequently over enrolled patients. Thus, we surveyed power calculations in publications of RCTs of biologics in rheumatoid arthritis (RA) to assess over enrollment. METHODS: A PubMed search identified 40 reports of original RCTs testing the efficacy of infliximab, etanercept, adalimumab, abatacept, rituximab and tocilizumab in patients with RA. As a first analysis, based on a two equal arms study with an alpha error of 0·05 and a power of 80% and of 90%, recalculation of the sample size was performed using the primary outcome results. In the second analysis, only those studies with equal number of patients in both arms and also in which all elements of a power calculation were given, were considered. New sample sizes were calculated based on the presented power elements in the related publications. RESULTS: In the first analysis, when we assigned a power of 80% and of 90%, 32 of 40 (80%) studies enrolled more than required number of patients, with a mean 131 ± 147 (SD), and 31 of 40 (78%) studies having had enrolled extra patients, with a mean 121 ± 147 (SD) in their treatment arms, respectively. Eleven studies qualified for the second analysis. There were still more patients with a mean of 48 ± 30 (SD) extra patients enrolled in the treatment arms. CONCLUSION: Most RCTs in RA enrol more patients than needed. This is costly and has the immediate consequence of exposing needless number of patients to potential harm.
23223892 [Synovialitis of the arthrofibrotic type: criteria of a new synovialitis type for the diag 2013 Apr After rheumatologic conservative medical therapy has been exhausted in degenerative and inflammatory joint diseases, arthroplastic operations are an important option to restore quality of life. Endoprosthesis-associated arthrofibrosis is a severe fibrosing disease of the synovial membrane after endoprosthetic operations. Neither the morphological substrate nor histopathological criteria have been described. The aim was to describe the histopathological substrate of arthrofibrosis and to define histological and immunohistochemical criteria of arthrofibrosis on the basis of tissue samples derived from revision. In histopathological analyses arthrofibrosis revealed a synovialitis with varying fibrosis, without detectable ossification and without minimal wear particle reaction (so-called synovialitis of arthrofibrotic type, SAT). A 3-stage grading was determined based on the cellular density of the fibrous tissue (fibroblast cellularity). In 191 cases with SAT, grade 1 was found in 24.1 % (n = 46), grade 2 was found in 51.8 % (n = 99) and grade 3 was found in 24.1 % (n = 46). The control group consisted of 29 cases with synovialitis of indifferent type (type IV membrane). If SAT grades 2 and 3 are summed together, i.e. the distance between the fibroblasts was less than two cell lengths, the difference of the fibroblast cellularity compared with the type IV membrane was significant (p < 0.001). Above SAT grade 2 the diagnosis of arthrofibrosis could be made with a sensitivity 0.7592 and specificity 0.8276. The SM-alpha-actin cytoplasmic positivity of fibroblasts indicates a myofibroblast phenotype and the β-catenin positivity suggests a resemblance to fibromatosis or a keloid-like process. In the quantitative evaluation of the β-catenin positive fibroblasts, there was a significant difference (p < 0.001) between type IV membrane and SAT. A threshold value of 20 beta-catenin positive cells per microscopic high power field (HPF) was determined, which represents in conjunction with the clinical information a new histopathological diagnosis component (sensitivity 0.720, specificity 0.867).
23548127 Bauhinia championii extraction treatment of collagen-induced arthritis via downregulation 2013 Rheumatoid arthritis (RA) has emerged as an important worldwide public health problem. Due to the lack of efficacy and major side effects related to many Western medical treatments, traditional Chinese medicine or herbal medicine is very often used to treat this disease. In the present study, we evaluated the effects of Bauhinia championii (Benth.) Benth. extraction (BCBE) in a rat model of RA induced by type-II collagen. Wistar rats with type-II collagen-induced arthritis (CIA) were given either 125 or 500 mg/kg of BCBE for RA. Paw swelling and weight were measured, and pathological joint sections of CIA rats were observed using the hematoxylin and eosin (HE) staining method. Protein and mRNA expression of toll-like receptor-4 (TLR4), myeloid differentiation factor 88 (MyD88) and nuclear transcription factor κB (NF-κB) were determined by western blot analysis and reverse transcription-polymerase chain reaction (RT-PCR) analysis in synovial tissue. During therapeutic treatment, BCBE significantly suppressed paw swelling, increased weight loss and ameliorated pathological joint changes. The protein and mRNA expressions of TLR4, MyD88 and NF-κB were downregulated in the CIA model when treated with BCBE. In conclusion, these results suggest that the treatment of RA with BCBE confers anti-RA activity and has therapeutic potential in this CIA model.
25499175 Association of Toll like receptor Asp299Gly with rheumatoid arthritis risk: a systematic r 2015 Mar OBJECTIVE: Rheumatoid arthritis (RA) is thought to be triggered by various genetic and environmental factors. Few human epidemiologic studies demonstrated that single nucleotide polymorphisms (SNPs) in Toll-like receptor (TLR) genes are associated with RA. We aimed to evaluate the effects of TLR polymorphisms on the risk of RA pathogenesis by using a meta-analysis approach. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, a systematic search and meta-analysis of the literature was conducted. We screened the medical literature based on keywords search in MEDLINE and EMBASE 'Toll-like receptor', 'polymorphism', and rheumatoid arthritis. Meta-analyses were performed under the random-effects model by using: (1) recessive, (2) homozygous, (3) dominant, (4) codominant and allele contrast models. RESULTS: A total of 3086 cases and 3756 controls in nine studies were included in the meta-analysis. Association between TLR4 Asp299Gly and RA risk was marginally significant [OR = 0.856 (95% CI, 0.716-1.022); P = 0.086] in the homozygous model. AA and GG homozygote genotypes tended to be significant protective factors against RA risk. CONCLUSION: Our overall analyses indicated that TLR4 Asp299Gly polymorphism might contribute to RA pathogenesis.
23070807 Activities of enzymes that hydrolyze adenine nucleotides in lymphocytes from patients with 2013 Jul The purpose of this study was to investigate the activities of ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase; EC 3.6.1.5; CD39) and adenosine deaminase (E-ADA; EC 3.5.4.4) in lymphocytes from patients with rheumatoid arthritis (RA). Thirty patients diagnosed with RA through American College of Rheumatology criteria as well as 30 healthy patients were selected. Peripheral blood lymphocytes were isolated, and E-NTPDase and E-ADA activities were assayed. The results demonstrated an increased E-NTPDase activity (both ATP and ADP as substrates) and a decreased E-ADA activity in RA patients. These data suggest an organic effort to preserve the adenosine level, which is known to have anti-inflammatory and analgesic properties, working as a potent suppressor of immune response.
24291654 Mortality in rheumatoid arthritis: the impact of disease activity, treatment with glucocor 2015 Feb OBJECTIVES: To investigate the impact of disease activity, the course of the disease, its treatment over time, comorbidities and traditional risk factors on survival. METHODS: Data of the German biologics register RABBIT were used. Cox regression was applied to investigate the impact of time-varying covariates (disease activity as measured by the DAS28, functional capacity, treatment with glucocorticoids, biologic or synthetic disease modifying antirheumatic drugs (DMARDs)) on mortality after adjustment for age, sex, comorbid conditions and smoking. RESULTS: During 31 378 patient-years of follow-up, 463 of 8908 patients died (standardised mortality ratio: 1.49 (95% CI 1.36 to 1.63)). Patients with persistent, highly active disease (mean DAS28  > 5.1) had a significantly higher mortality risk (adjusted HR (HRadj)=2.43; (95% CI 1.64 to 3.61)) than patients with persistently low disease activity (mean DAS28 < 3.2). Poor function and treatment with glucocorticoids > 5 mg/d was significantly associated with an increased mortality, independent of disease activity. Significantly lower mortality was observed in patients treated with tumour necrosis factor α (TNFα) inhibitors (HRadj=0.64 (95% CI 0.50 to 0.81), rituximab (HRadj=0.57 (95% CI 0.39 to 0.84), or other biologics (HRadj=0.64 (95% CI 0.42 to 0.99), compared to those receiving methotrexate. To account for treatment termination in patients at risk, an HRadj for patients ever exposed to TNFα inhibitors or rituximab was calculated. This resulted in an HRadj of 0.77 (95% CI 0.60 to 0.97). CONCLUSIONS: Patients with long-standing high disease activity are at substantially increased risk of mortality. Effective control of disease activity decreases mortality. TNFα inhibitors and rituximab seem to be superior to conventional DMARDs in reducing this risk.
24187101 COMP-C3b complexes in rheumatoid arthritis with severe extraarticular manifestations. 2013 Dec OBJECTIVE: To investigate biomarker patterns in rheumatoid arthritis (RA) with extraarticular manifestations. METHODS: Cartilage oligomeric matrix protein (COMP), COMP-C3b, and soluble terminal complement complexes (sTCC) were measured by ELISA. RESULTS: COMP-C3b levels were higher in patients with RA than in healthy controls and lower in extraarticular RA (ExRA) than in RA controls. In patients with ExRA, sTCC levels were higher than in RA controls, and correlated inversely with serum COMP-C3b levels in the ExRA group. CONCLUSION: Patients with ExRA had lower levels of COMP-C3b. This may be a consequence of complement consumption or a lower potential for COMP from these patients to activate complement.