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ID PMID Title PublicationDate abstract
22253026 Fas-associated death domain protein and adenosine partnership: fad in RA. 2012 Jun Inflammation is the principal hallmark of RA. Different pathways are implicated in the production of pro-inflammatory cytokines, the bona fide mediators of this inflammation. Among them are the TNF pathway and the IL-1 receptor/Toll-like receptor (IL-1R/TLR4) pathway. One of the potential negative regulators of IL-1R/TLR4 signalling is the Fas-associated death domain protein (FADD), which is the pivotal adaptor of the apoptotic signal mediated by death receptors of the TNF family. FADD can sequester myeloid differentiation primary response gene 88 (MyD88), the common adaptor of most TLRs, and hence hinder the activation of nuclear factor κB (NF-κB), the downstream transcription factor. We recently described a new regulatory mechanism of FADD expression, via the shedding of microvesicles, mediated by adenosine receptors. Interestingly, adenosine is found in high concentrations in the joints of RA patients and has been largely reported as a regulator of inflammation. This review discusses the possible link that could exist between the adenosine-dependent regulation of FADD in the inflammatory context of RA and the potential role of FADD as a therapeutic target in the treatment of RA. We will see that the modulation of FADD expression may be a double-edged sword by increasing apoptosis and at the same time limiting NF-κB activation.
22090005 Evaluating hand in systemic sclerosis. 2012 Nov Articular symptoms are common in SSc and joint pain is a frequent presenting feature of this disease. Hand involvement is often the first clinical manifestation of SSc and could be resulted from fibrosis or synovitis or an overlap syndrome with rheumatoid arthritis (RA); though, the latter is a controversy in practice. To define the clues when identifying the nature of the hand arthropathy in SSc. In order to determine the hand arthropathy, serological tests, hand radiography, finger-to-palm (FTP) distance and other clinical features, disease activity and functional scoring parameters were assessed. Twenty-eight consecutive SSc patients and 43 controls (21 rheumatoid arthritis and 22 healthy controls) were included. Radiographic findings in SSc patients were: Erosions 25%, joint space narrowing 17.9%, arthritis 10.7%, radiological demineralisation 42.9%, acro-osteolysis 25%, flexion contracture 28.6% and calcinosis 17.9%. Anti-CCP antibody and RF positivity were as follows: In SSc group: 3 (11%) and 7 patients (25%); In RA group: 13 (62%) and 19 patients (90.5%); In healthy control group: 1 (4%) and 3 persons (13.6%), respectively. Two patients (7.14%) were regarded as RA overlap, whom both had positive RF and positive anti-CCP results and their radiographs revealed arthritis. Seventeen patients (61%) were regarded as SSc arthropathy; all were negative for RF and anti-CCP but revealed nonarthritic radiological findings. (Among them, only one patient had positive anti-CCP result). The remainder (9 patients) had no radiological or serological finding positive for arthropathy. Arthritis was found to have correlation with heart involvement and FTP was correlated with lung involvement. Hand involvement in SSc is a challenge in rheumatology practice; Radiographic testing when evaluated with RF and anti-CCP will be a helpful tool to discriminate SSc arthropathy from RA-SSc overlap. Hand arthropathy should increase the interest in the serious internal organ involvements of SSc.
21532055 Preferential accumulation of activated Th1 cells not only in rheumatoid arthritis but also 2011 Aug OBJECTIVE: It was previously found that Th1 but not Th17 cells were predominant in the joints of rheumatoid arthritis (RA). To verify whether this is a unique feature of CD4 T cells in RA joints, we performed comparative flow cytometric analysis of CD4 T cells in RA and osteoarthritis (OA) joints. METHODS: Mononuclear cells were isolated from peripheral blood (PB), synovial membrane (SM), and synovial fluid (SF) from a total of 18 RA and 12 OA patients. The expression of surface molecules and cytokine production of CD4 T cells was examined by a flow cytometer. RESULTS: Most CD4 T cells in RA joints expressed memory/activation markers, such as CD45RO, HLA-DR, and CD69. CCR5 was highly expressed on CD4 T cells in SF but not in PB or SM. With regard to Th17-related molecules, CD4 T cells expressing CCR6 were not enriched in either SF or SM. In contrast, CD161-positive cells were abundant in the joint, many of which, however, produced interferon-γ but not interleukin 17A. Virtually all T cells in OA joints, although much less numerous than in RA joints, expressed activation markers. Th1 cells were predominant in both OA and RA joints, while there were a few Th17 cells. The frequency of Th17 cells in the joint tended to be lower in OA than RA. CONCLUSION: There was a quantitative but not qualitative difference in CD4 T cells, including the expression of activation markers and cytokine profiles, between RA and OA joints.
22854883 Ethnic differences in the prognostic utility of rheumatoid factor isotypes and anticyclic 2013 Jul OBJECTIVES: The prognostic significance of rheumatoid factor (RF) and anticyclic citrullinated peptide antibody (anti-CCP) in rheumatoid arthritis (RA) remains contentious due to the conflicting lines of evidence. This study aims to determine the association between RF isotypes and anti-CCP with disease severity in RA patients from three ethnic groups. METHODS: A total of 147 RA patients from three different ethnic groups (Malays, Chinese, and Indians) who fulfilled the 1987 American College of Rheumatology (ACR) revised criteria for RA were recruited into this study. The seroprevalence of RF isotypes immunoglobulin (Ig)A, IgG, and IgM, as well as anti-CCP was determined using commercial enzyme-linked immunosorbent assay (ELISA) kits. Multinomial regression analysis was performed to assess the independent effects of autoantibody status on the development of deforming and erosive RA and the presence of extra-articular manifestations (EAM). RESULTS: In Chinese patients, we found a significant association (p < 0.05) between IgG RF and anti-CCP and the presence of erosive disease, as well as IgM RF and IgG RF with the presence of joint deformities. In Indian patients, IgM RF was associated with deforming disease, whereas none of the antibodies were associated with disease severity in Malay patients. Multinomial regression analysis revealed that IgG RF was the most important predictor variable for erosive disease in Chinese patients, and IgM RF the only predictor variable associated with deforming disease in both Chinese and Indian RA patients. CONCLUSIONS: There is variability in the phenotypic association of RF isotypes and anti-CCP in relation to disease severity of RA in the three ethnic groups. RF, in particular, IgG and IgM, may be better prognosticators of severe disease in Chinese and Indian patients.
21952740 Replication of association of the PTPRC gene with response to anti-tumor necrosis factor t 2012 Mar OBJECTIVE: Several rheumatoid arthritis (RA) susceptibility variants map close to genes involved in the tumor necrosis factor (TNF) signaling pathway, prompting the investigation of RA susceptibility variants in studies of predictors of response to TNF blockade. Based on a previously reported association of RA with the PTPRC genetic locus, the present study was undertaken to test established RA susceptibility variants, including PTPRC, in the prediction of response to TNF blockade in a large cohort of patients from the UK. METHODS: DNA was extracted from the blood of 1,115 UK patients with RA who were receiving anti-TNF biologic therapy. Samples were analyzed for 29 single-nucleotide polymorphisms (SNPs) previously established as RA susceptibility variants. In the primary analysis, the effect of each SNP on treatment response was assessed by linear regression, using an additive model, in which absolute change in the Disease Activity Score in 28 joints at 6 months of followup was the outcome measure. In a secondary analysis, logistic regression models were used to compare patients with a good treatment response (n = 274) to those with a poor response (n = 195), as defined using the European League Against Rheumatism response criteria. Results were combined with those from previous studies to confirm the findings by meta-analysis. RESULTS: The PTPRC rs10919563 SNP was associated with improved treatment response in both the primary analysis (regression coefficient 0.19, 95% confidence interval [95% CI] 0.09, 0.37; P = 0.04) and secondary analysis (odds ratio 0.62, 95% CI 0.40, 0.95; P = 0.03). A meta-analysis combining these data with the results from a previous study strengthened the evidence for association with the PTPRC SNP (P = 5.13 × 10(-5) ). No convincing association of the treatment response with other candidate loci was detected. CONCLUSION: Presence of the rs10919563 RA susceptibility variant at the PTPRC gene locus predicts improved response to anti-TNF biologic therapy. Fine-mapping studies are required to determine whether this SNP or another variant at the locus provides the greatest predictive accuracy for treatment response.
21398331 Rheumatoid arthritis susceptibility genes associate with lipid levels in patients with rhe 2011 Jun INTRODUCTION: Rheumatoid arthritis (RA), a systemic inflammatory disease with complex genetic aetiology, associates with excess cardiovascular morbidity and mortality. Dyslipidaemia, a major cardiovascular risk factor has been reported to predate the onset of RA, thus suggesting a potential genetic link between the two conditions. The authors assessed whether RA susceptibility genes associate with the presence of dyslipidaemia in RA patients. METHODS: 400 well-characterised RA patients were included in this cross-sectional study. Fasting lipid profile (total cholesterol, high-density lipoproteins (HDL), low-density lipoproteins (LDL), triglycerides, apolipoproteins (ApoA and ApoB) and lipoprotein (a)) and four RA susceptibility genes (PTPN22, TRAF1/C5, STAT4 and human leucocyte antigen shared epitope (HLA-SE)) were assessed and associations were sought in both univariate and multivariate analyses. RESULTS: Following adjustment for age, sex and erythrocyte sedimentation rate, the G allele of TRAF1/C5 associated with lower total cholesterol (p=0.010), LDL (p=0.022) and ApoB (p=0.014); one or more copies of the shared epitope associated with lower ApoA (p=0.035) and higher ApoB:ApoA ratio (p=0.047); while STAT4 TT homozygotes had higher lipoprotein (a) (p=0.004). CONCLUSIONS: RA susceptibility genes (TRAF1/C5, STAT4 and HLA-DRB1-SE) may be involved in the regulation of lipid metabolism in RA patients, thus contributing to cardiovascular disease (CVD) risk and adverse outcome. If these findings are replicated, such genotyping could be used to identify and target for prevention those RA patients most at risk of CVD. It will also be interesting to study the association of these genes with lipid levels in the general population and identify mechanisms to explain the link.
22178253 [Can the medication in patients with rheumatoidarthritis in remission be stopped?]. 2012 Jan Rheumatoid arthritis is a chronic systemic inflammatory disease that causes significant morbidity and mortality. The combined use of methotrexate and biological agents directed against tumor necrosis factor (TNF) has achieved significant improvement in clinical, radiographic and functional parameters not seen previously and has revolutionized the therapeutic goal of achieving remission in clinical, structural and functional parameters. The next goal should be to achieve remission without the use of biological drugs and later without medication. Although there is evidence about the efficacy and safety of TNF inhibitors, there is none on remission without the use of biological agents or disease modifying drugs.
23083981 Reprint of BMCL_19101. 2012 Nov 15 The pathogenesis of rheumatoid arthritis is mainly driven by NF-κB-mediated production of cytokines, such as TNF-α. We report herein that the orally available imidazoline-based NF-κB inhibitor, TCH-013, was found to significantly reduce TNF-α signaling and attenuate collagen antibody induced arthritis in BALB/c mice.
22835600 Omega-3 polyunsaturated fatty acids and the treatment of rheumatoid arthritis: a meta-anal 2012 Jul BACKGROUND AND AIMS: We undertook this study to assess the effects of omega-3 polyunsaturated fatty acids (PUFAs) (administered at ≥2.7 g/day) for a minimum duration of 3 months on clinical outcomes in patients with rheumatoid arthritis (RA). METHODS: The authors surveyed randomized controlled trials (RCTs) that examined the effects of omega-3 PUFAs on clinical outcomes in RA patients using Medline and the Cochrane Controlled Trials Register and by performing manual searches. Meta-analysis of RCTs was performed using fixed and random effects models. Outcomes are presented as standardized mean differences (SMD). RESULTS: Ten RCTs involving 183 RA patients and 187 placebo-treated RA controls were included in this meta-analysis. The analysis showed that omega-3 PUFAs clearly reduced nonsteroidal anti-inflammatory drug (NSAID) consumption (SMD -0.518, 95% CI -0.915 to -0.121, p = 0.011) without between-study heterogeneity (I(2) = 0%). Tender joint count (SMD -0.214, 95% CI-0.489-0.062, p = 0.128), swollen joint count (SMD -0.170, 95% CI-0.454-0.114, p = 0.241), morning stiffness (SMD -0.224, 95% CI-0.955-0.212, p = 0.221), and physical function (SMD 0.264, 95% CI-0.232-0.724, p = 0.314) showed a trend to improve more in patients treated with omega-3 PUFAs than in placebo-treated controls, but they did not reach statistical significance. CONCLUSIONS: This meta-analysis suggests that the use of omega-3 PUFAs at dosages >2.7 g/day for >3 months reduces NSAID consumption by RA patients. Further studies are needed to explore the clinical and NSAID-sparing effects of omega-3 PUFAs in RA.
21557439 Patient evaluation of a novel patient education leaflet about heart disease risk among peo 2011 Dec OBJECTIVES: People with rheumatoid arthritis (RA) require access to clear and consistent information about their condition, and Arthritis Research UK produces a wide range of leaflets to meet this need. There is no patient information leaflet about cardiovascular disease (CVD) in the context of having RA, despite the fact that CVD accounts for 50% of the mortality in RA. A leaflet was developed; this paper describes the patient evaluation of this novel education resource. METHODS: A questionnaire was developed to evaluate the leaflet's content, literacy, graphics, layout and ability to stimulate learning. It was distributed, with the leaflet, to 500 National Rheumatoid Arthritis Society members. RESULTS: There was a 72.8% response rate. Of the respondents: 96% agreed that the purpose of the leaflet was clear; 78% agreed that the leaflet was relevant to them; 96% agreed that they understood the leaflet; 53% agreed that the leaflet cover was appealing; 81% agreed that the size of the typing was suitable; 71% agreed that the advice was appropriate for their lifestyle. Omissions included adequately describing any risks associated with its advice, what sources of information were used to compile the leaflet and when this information was produced. Eighty-four per cent of respondents said that they would recommend this leaflet to other people with RA. Qualitatively, many people felt more empowered as a result of reading the leaflet. CONCLUSIONS: Patient evaluation of new educational resources is important and ensures that materials meet patients' needs and are presented in a user-friendly style. Ultimately, the test of the effectiveness of the leaflet will be if patients change their behaviour appropriately.
23264555 Association between -871C>T promoter polymorphism in the B-cell activating factor gene and 2013 Apr OBJECTIVE: To determine whether a functional single-nucleotide polymorphism in the B-cell activating factor (BAFF) gene correlates with the response to treatment with rituximab (RTX) in RA. METHODS: SMART is a randomized open trial (NCT01126541) assessing two strategies of re-treatment in patients responding to 1-g infusion of RTX with MTX on days 1 and 15 after failure, intolerance or contraindication to TNF blockers. Among the 224 patients included, 115 provided informed consent, could be genotyped and were included in an ancillary study of SMART assessing European League Against Rheumatism (EULAR) response rate after the first course of RTX according to BAFF-871C>T polymorphism. Baseline clinical factors (patients and disease characteristics) and biologic factors (ESR, CRP, RF, anti-citrullinated peptide antibodies, serum immunoglobulins) were collected. Univariate analyses were performed to assess whether BAFF-871C>T polymorphism was associated with EULAR response at week 24. Results with P < 0.15 obtained in univariate analyses were then included in multivariate analysis adjusted on DAS28 level. RESULTS: Ninety-three patients (81%) were responders, of whom 31 (27%) were good responders. CC genotype was significantly associated with a higher response rate [92% of responders vs 64% for TT genotype, odds ratio (OR) = 6.9; 95% CI 1.6, 29.6; P = 0.03]. These results were also confirmed in RF-positive patients (96% vs 58%, P = 0.006). In multivariate analysis, C allele carriage was independently associated with response to RTX (OR = 4.1; 95% CI 1.3, 12.7; P = 0.017). CONCLUSION: The BAFF-871C>T polymorphism seems to influence the response to RTX in RA patients after failure or intolerance to TNF blockers.
23148635 Genetic variation in the SLC19A1 gene and methotrexate toxicity in rheumatoid arthritis pa 2012 Nov AIM: We investigated the clinical relevance of SLC19A1 genetic variability for methotrexate (MTX) toxicity in rheumatoid arthritis patients using a haplotype-based approach. PATIENTS & METHODS: Two hundred and twelve unrelated rheumatoid arthritis patients and 89 lymphoblastoid cell lines were used to investigate the effect of SLC19A1 SNPs and haplotypes on MTX adverse events and treatment discontinuation. RESULTS: Two putatively functional SNPs in high linkage disequilibrium, rs1051266 and rs1131596, were associated with protection (hazard ratio: 0.33; 95% CI: 0.16-0.69; adjusted p = 0.021 and hazard ratio: 0.38; 95% CI: 0.17-0.27; adjusted p = 0.021, respectively) of discontinuation of MTX treatment owing to toxicity. These SNPs were also associated with protection from infections. SLC19A1 haplotype analysis found significant associations with MTX discontinuation owing to toxicity (p = 0.025). Quantification of SLC19A1 mRNA in cell lines suggested that rs1131596 was not a major causal variant. CONCLUSION: Individual SNP and haplotype analyses suggest that rs1051266 could be a functional variant altering MTX toxicity; however, validation in independent studies is needed.
21879377 Evaluation of apoptosis-related gene Fas (CD95) and FasL (CD178) polymorphisms in Iranian 2012 Sep Apoptosis signals are essential for establishing homeostasis and adequate immune response. Dysregulation of apoptosis-related genes in the immune system, which could be due to gene polymorphisms, conduct to autoimmune diseases including rheumatoid arthritis. In the current study, the apoptosis-related gene Fas_-670A>G, FasL_844C>T, and FasLIVS2nt_124A>G polymorphisms were genotyped in 120 Iranian patients with rheumatoid arthritis (RA) and 112 unrelated healthy controls using PCR-RFLP method. Among the 120 RA patients being heterozygous in the promoter region of Fas_-670A/G (OR 1.42,CI 0.92-1.52, P = 0.18) and FasL_-844C/T (OR 1.42, CI 0.92-1.52, P = 0.18) and homozygous in the minor allele for FasLIVS2nt_124G/G (OR 1.43, CI 0.76-1.81, P = 0.7), the frequency of these polymorphisms is higher in the cases than in controls and the elevated risk of RA were observed when the patient compared with controls, although this is not statistically significant.
22802155 Peripheral and central mechanisms of fatigue in inflammatory and noninflammatory rheumatic 2012 Dec Fatigue is a common symptom in a large number of medical and psychological disorders, including many rheumatologic illnesses. A frequent question for health care providers is related to whether reported fatigue is "in the mind" or "in the body"-that is, central or peripheral. If fatigue occurs at rest without any exertion, this suggests psychological or central origins. If patients relate their fatigue mostly to physical activities, including exercise, their symptoms can be considered peripheral. However, most syndromes of fatigue seem to depend on both peripheral and central mechanisms. Sometimes, muscle biopsy with histochemistry may be necessary for the appropriate tissue diagnosis, whereas serological tests generally provide little reliable information about the origin of muscle fatigue. Muscle function and peripheral fatigue can be quantified by contractile force and action potential measurements, whereas validated questionnaires are frequently used for assessment of mental fatigue. Fatigue is a hallmark of many rheumatologic conditions, including fibromyalgia, myalgic encephalitis/chronic fatigue syndrome, rheumatoid arthritis, systemic lupus, Sjogren's syndrome, and ankylosing spondylitis. Whereas many studies have focused on disease activity as a correlate to these patients' fatigue, it has become apparent that other factors, including negative affect and pain, are some of the most powerful predictors for fatigue. Conversely, sleep problems, including insomnia, seem to be less important for fatigue. There are several effective treatment strategies available for fatigued patients with rheumatologic disorders, including pharmacological and nonpharmacological therapies.
23124085 [A case of Sjögren syndrome suspected, rheumatoid arthritis and Behcet's disease complica 2012 We described a patient with secondary Sjögren's syndrome suspected showing multiple cranial neuropathies at the different time. A 68-year old woman has been treated as rheumatoid arthritis since 1963. In 2001, she was also diagnosed with Sjögren's syndrome suspected. Afterward, abducent and trigeminal neuropathies and uveites occurred. This case is important to insight into the cranial neuropathy with Sjögren's syndrome.
22183986 Brief report: airways abnormalities and rheumatoid arthritis-related autoantibodies in sub 2012 Jun OBJECTIVE: To evaluate the presence of pulmonary abnormalities in rheumatoid arthritis (RA)-related autoantibody-positive subjects without inflammatory arthritis. METHODS: Forty-two subjects who did not have inflammatory arthritis but were positive for anti-cyclic citrullinated peptide antibodies and/or ≥2 rheumatoid factor isotypes (a profile that is 96% specific for RA), 15 autoantibody-negative controls, and 12 patients with established seropositive early RA (<1-year duration) underwent spirometry and high-resolution computed tomography (HRCT) lung imaging. RESULTS: The median age of autoantibody-positive subjects was 54 years, 52% were female, and 38% were ever-smokers; these characteristics were not significantly different from those of autoantibody-negative control subjects. No autoantibody-positive subject had inflammatory arthritis based on joint examination. HRCT revealed that 76% of autoantibody-positive subjects had airways abnormalities including bronchial wall thickening, bronchiectasis, centrilobular opacities, and air trapping, compared with 33% of autoantibody-negative controls (P = 0.005). The prevalence and type of lung abnormalities among autoantibody-positive subjects were similar to those among patients with early RA. In 2 autoantibody-positive subjects with airways disease, inflammatory arthritis classifiable as articular RA developed ∼13 months after the lung evaluation. CONCLUSION: Airways abnormalities that are consistent with inflammation are common in autoantibody-positive subjects without inflammatory arthritis and are similar to airways abnormalities seen in patients with early RA. These findings suggest that the lung may be an early site of autoimmune-related injury and potentially a site of generation of RA-related autoimmunity. Further studies are needed to define the mechanistic role of lung inflammation in the development of RA.
21345216 Validation of rheumatoid arthritis diagnoses in health care utilization data. 2011 Feb 23 INTRODUCTION: Health care utilization databases have been increasingly used for studies of rheumatoid arthritis (RA). However, the accuracy of RA diagnoses in these data has been inconsistent. METHODS: Using medical records and a standardized abstraction form, we examined the positive predictive value (PPV) of several algorithms to define RA diagnosis using claims data: A) at least two visits coded for RA (ICD-9, 714); B) at least three visits coded for RA; and C) at least two visits to a rheumatologist for RA. We also calculated the PPVs for the subgroups identified by these algorithms combined with pharmacy claims data for at least one disease-modifying anti-rheumatic drug (DMARD) prescription. RESULTS: We invited 9,482 Medicare beneficiaries with pharmacy benefits in Pennsylvania to participate; 2% responded and consented for review of their medical records. There was no difference in characteristics between respondents and non-respondents. Using 'RA diagnosis per rheumatologists' as the gold standard, the PPVs were 55.7% for at least two claims coded for RA, 65.5% for at least three claims for RA, and 66.7% for at least two rheumatology claims for RA. The PPVs of these algorithms in patients with at least one DMARD prescription increased to 86.2%-88.9%. When fulfillment of 4 or more of the ACR RA criteria was used as the gold standard, the PPVs of the algorithms combined with at least one DMARD prescriptions were 55.6%-60.7%. CONCLUSIONS: To accurately identify RA patients in health care utilization databases, algorithms that include both diagnosis codes and DMARD prescriptions are recommended.
21352592 Adalimumab reduces hand bone loss in rheumatoid arthritis independent of clinical response 2011 Feb 27 BACKGROUND: Anti-TNF therapy has been shown to reduce radiographic joint damage in rheumatoid arthritis (RA) independent of clinical response. This has previously not been examined for periarticular bone loss, the other characteristic feature of bone involvement in RA.The objective of this study was to examine if treatment with the TNF-α inhibitor adalimumab also could reduce periarticular bone loss in RA patients independent of disease activity. METHODS: RA patients were recruited from the PREMIER study and included 214 patients treated with methotrexate (MTX) plus adalimumab and 188 patients treated with MTX monotherapy. Periarticular bone loss was assessed by digital X-ray radiogrammetry metacarpal cortical index (DXR-MCI). Change in DXR-MCI was evaluated in patients with different levels of clinical response, as assessed by changes in DAS28 score at 52 weeks and in mean C-reactive protein (CRP) levels during follow-up. RESULTS: In the MTX group, there was a greater median DXR-MCI loss among patients with moderate and high disease activity compared to those in remission or with low disease activity (-3.3% vs. -2.2%, p = 0.01). In contrast, periarticular bone loss was independent of disease activity (-1.9% vs. -2.4%, p = 0.99) in the combination group. In the MTX group patients with a mean CRP of ≥ 10 mg/l lost significantly more DXR-MCI than patients with low CRP (-3.1% vs. -1.9%, p <0.01) whereas in the combination group no significant differences between the two CRP groups was seen (-2.4% vs. -2.0%, p = 0.48). CONCLUSION: Adalimumab in combination with MTX reduces periarticular bone loss independently of clinical response. These results support the hypothesis that TNF-α stimulates the osteoclast not only by the inflammatory pathway but do also have a direct effect on the osteoclast. TRIAL REGISTRATION: ClinicalTrials (NCT): NCT001195663.
21750000 Combining anti-cyclic citrullinated peptide with the American College of Rheumatology 1987 2011 Oct OBJECTIVES: To test the performances of combining anti-CCP second generation (CCP2) with ACR 1987 classification criteria and to diagnose early RA in a community-based very early arthritis (VErA) patient cohort. METHODS: The VErA cohort comprised 310 patients (median age 52 years; 68.1% women; median symptom duration 4.2 months; glucocorticoid- and DMARD naïve) conservatively treated during the first 2 years. At 6 years of follow-up, a three-expert committee classified the patients into three groups: RA, other classified arthritis (OCA) or unclassified arthritis (UA). We calculated the performances of the different sets, including anti-CCP2 positivity, while retaining or deleting RF and rheumatoid nodule components with ACR 1987 criteria for early RA diagnosis. Models were subjected to receiver operating characteristics curve and logistic regression analyses to try to identify relevant sets able to classify very early RA. RESULTS: At 6 years, 149 patients were diagnosed as RA and 119 as non-RA (95 OCA and 24 UA). The original ACR 1987 criteria had 77.9% sensitivity and 64.7% specificity for the RA diagnosis at 6 years. The modified set excluding rheumatoid nodules, including anti-CCP2 positivity and retaining RF performed significantly better than ACR 1987 criteria, with 79.9% sensitivity and 64.7% specificity and with a larger area under the curve. However, in the zone of interest, i.e., ≥4/7 criteria, the curves for these sets were superimposed. CONCLUSIONS: Adding anti-CCP2 positivity and deleting rheumatoid nodules failed to improve the performances of ACR 1987 classification criteria for the diagnosis of early RA.
21829083 [B-cell lymphoma possessing t(14;18)(q32;q21)in a patient with rheumatoid arthritis receiv 2011 Aug There is evidence of a slight increase in malignant lymphoma among rheumatoid arthritis(RA)patients receiving methotrexate( MTX). Increased rates of lymphoma have been attributed to reactivation of the Epstein-Barr virus(EBV). A 72-yearold woman was admitted to our hospital for generalized lymph adenopathy. She suffered from RA and has been treated with MTX for 7 years; the total amount of MTX received was around 2, 700 mg. The cervical lymph node revealed a diffuse proliferation of large atypical lymphocytes. An immunophenotype revealed CD10+, CD19+, CD20+, and k+. The chromosome analysis showed a complex abnormality containing t(14;18)(q32;q21). The tumor cells were positive for EBV sequences by in situ hybridization(ISH). A rituximab containing regimen was effective, but a systemic relapse occurred 4 years later. The biopsied sample was diagnosed as diffuse large B-cell lymphoma. FISH analysis revealed positive for t(14;18)(q32;q21), however, EBV was negative using ISH. In general, the concurrence of t(14;18)(q32;q21)and EBV in the B-cell lymphoma is rare. In addition, the negative change in EBV in the relapsed lymphoma cells revealed a quite rare phenomenon.