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ID PMID Title PublicationDate abstract
22052031 The antinociceptive efficacy of HWTX-I epidurally administered in rheumatoid arthritis rat 2011 Nov Rheumatoid arthritis (RA) is one of the inflammatory kinds of arthritis in the clinical situation, and cytosolic Ca2+ overload has been proposed as one of the primary factors for many inflammatory cells activation, which lead to relative enzymes and inflammatory factors release. It is therefore accepted that Ca2+ channel blockers can protect joint injury from inflammation. In the present study we investigated the possible molecular mechanism of the antinociceptive efficacy of HWTX-I, a spider peptide toxin blocking Ca2+ channels, on the rat rheumatoid arthritis model. Our study demonstrates that HWTX-I can relieve pain in the inflammatory joints and eliminate arthrocele to some degree. Moreover, HWTX-I can also decrease the concentration of tumour necrosis factor α (TNF-α) and increase the concentration of interleukin 4(IL-4) and interleukin 10(IL-10) in rat's serum. HWTX-I can also decrease the mRNA expression level of related factors of TNF-α, interleukin 1β (IL-1β) and interleukin 6(IL-6) in inflammatory pathways in rheumatoid arthritis. Therefore, the present results show that the epidural administration of HWTX-I is effective in antinociception in the rat model of rheumatoid arthritis, which may act through its inhibition on certain inflammatory pathways.
22388997 Inflammation assessment in patients with arthritis using a novel in vivo fluorescence opti 2012 Apr BACKGROUND: Indocyanine green (ICG)-enhanced fluorescence optical imaging (FOI) is an established technology for imaging of inflammation in animal models. In experimental models of arthritis, FOI findings corresponded to histologically proven synovitis. This is the first comparative study of FOI with other imaging modalities in humans with arthritis. METHODS: 252 FOI examinations (Xiralite system, mivenion GmbH, Berlin, Germany; ICG bolus of 0.1 mg/kg/body weight, sequence of 360 images, one image per second) were compared with clinical examination (CE), ultrasonography (US) and MRI of patients with arthritis of the hands. RESULTS: In an FOI sequence, three phases could be distinguished (P1-P3). With MRI as reference, FOI had a sensitivity of 76% and a specificity of 54%, while the specificity of phase 1 was 94%. FOI had agreement rates up to 88% versus CE, 64% versus greyscale US, 88% versus power Doppler US and 83% versus MRI, depending on the compared phase and parameter. FOI showed a higher rate of positive results compared to CE, US and MRI. In individual patients, FOI correlated significantly (p<0.05) with disease activity (Disease Activity Score 28, r=0.41), US (r=0.40) and RAMRIS (Rheumatoid Arthritis MRI Score) (r=0.56). FOI was normal in 97.8% of joints of controls. CONCLUSION: ICG-enhanced FOI is a new technology offering sensitive imaging detection of inflammatory changes in subjects with arthritis. FOI was more sensitive than CE and had good agreement with CE, US in power Doppler mode and MRI, while showing more positive results than these. An adequate interpretation of an FOI sequence requires a separate evaluation of all phases. For the detection of synovitis and tenosynovitis, FOI appears to be as informative as 1.5 T MRI and US.
21413944 Antibodies to a new viral citrullinated peptide, VCP2: fine specificity and correlation wi 2011 Jun Anti-citrullinated protein/peptide antibodies (ACPA) are a hallmark of rheumatoid arthritis (RA) and can be measured using different citrullinated substrates. In this paper we describe a new viral citrullinated peptide - VCP2 - derived from the Epstein-Barr virus-encoded protein EBNA-2 and analyse its potential as substrate for ACPA detection. Analysing sera from 100 RA patients and 306 controls, anti-VCP2 immunoglobulin (Ig)G were found in 66% of RA sera, IgM in 46% and IgA in 39%, compared with less than 3% of control sera. Anti-VCP2 IgG was associated with erosive arthritis, the presence of rheumatoid factor and anti-VCP1 and anti-cyclic citrullinated peptide (CCP) antibodies. Anti-VCP2 antibodies were detected in 1% and anti-VCP1 antibodies in 4% of CCP-negative RA sera; conversely, 3% of the VCP-negative sera were CCP-positive. Taken together, these data suggest that VCP2 could offer a valuable tool for ACPA detection. Inhibition assays showed that two non-overlapping epitopes - a citrulline-glycine stretch shared between VCP1 and VCP2 and the N-terminal portion of the VCP2 sequence - were targeted by anti-VCP2 antibodies. Moreover, in some RA sera that tested positive in CCP and VCP2 assays, preincubation with VCP2 inhibited binding to CCP, whereas in other sera the binding was unaffected. Thus, the reactivity with more than one ACPA substrate might be due in some RA patients to antibody populations with different specificities, and in others to cross-reactive antibody populations. Finally, affinity-purified anti-VCP2 antibodies immunoprecipitated deiminated Epstein-Barr virus nuclear antigen (EBNA-2) from an EBNA-2-transfected cell line, suggesting that viral sequences may be involved in the generation of the ACPA response.
21989592 Impact of interactions of cigarette smoking with NAT2 polymorphisms on rheumatoid arthriti 2012 Mar OBJECTIVE: To examine whether polymorphisms in genes coding for drug-metabolizing enzymes (DMEs) have an impact on rheumatoid arthritis (RA) risk due to cigarette smoking in African Americans. METHODS: Smoking status was evaluated in African American patients with RA compared with non-RA controls, with smoking exposure categorized as heavy smoker (≥10 pack-years) versus never smoker/<10 pack-years. Individuals were genotyped for a homozygous deletion polymorphism in the M1 gene loci of glutathione S-transferase (GSTM1-null) in addition to tagging single-nucleotide polymorphisms (SNPs) in N-acetyltransferase 1 (NAT1), NAT2, and epoxide hydrolase 1 (EPXH1). Associations of these genotypes with RA risk were examined using logistic regression, and gene-smoking interactions were assessed. RESULTS: There were no significant associations of any DME genotype with RA. After adjustment for multiple comparisons, there were significant additive interactions between heavy smoking and the NAT2 SNPs rs9987109 (P(additive) = 0.000003) and rs1208 (P(additive) = 0.00001); the attributable proportion due to interaction ranged from 0.61 to 0.67. None of the multiplicative gene-smoking interactions examined remained significant with regard to overall disease risk, after adjustment for multiple testing. There was no evidence of significant gene-smoking interactions in analyses of GSTM1-null, NAT1, or EPXH1. DME gene-smoking interactions were similar when cases were limited to those patients who were positive for anti-citrullinated protein antibodies. CONCLUSION: Among African Americans, RA risk imposed by heavy smoking appears to be mediated in part by genetic variation in NAT2. While further studies are needed to elucidate the mechanisms underpinning these interactions, these SNPs appear to identify African American smokers at a much higher risk for RA, in whom the relative risk is at least 2-fold higher when compared to nonsmokers lacking these risk alleles.
21791546 Number and phenotype of rheumatoid arthritis patients' CD4+CD25hi regulatory T cells are n 2011 Oct OBJECTIVE: To analyse the therapeutic effects of etanercept (ETA) or adalimumab (ADA) on the numbers and phenotypes of CD4+CD25hi Tregs in RA patients. METHODS: RA patients received ADA (n = 28) or ETA (n = 20) and stable-dose MTX or LEF. Therapeutic responses were assessed with the 28-joint DAS (DAS-28) criteria after 12 weeks of treatment. Treg numbers and phenotypes, determined by flow cytometry using different gating strategies, were compared between responders and non-responders before and after 6 and 12 weeks of treatment. RESULTS: The percentages of good, moderate and non-responders among patients given ADA or ETA, respectively, were 46.5, 35.7 and 17.8% or 30, 20 and 50%, with respective mean (s.d.) pre-treatment CD4+CD25hi Treg percentages of 5.5 (0.04)% or 4.95 (0.02)%. Overall, for patients with active RA given ADA or ETA, neither TNF-α-blocking agent had an effect on Tregs percentage and absolute number. Moreover, CD4+CD25hi Treg counts remained unaffected in RA responders to ADA or ETA, compared with RA non-responders. Furthermore, the CD4+CD25hiCD45RA+, CD4+CD25hiCD45RO+ and CD4+CD25hiCD62L+ cell populations were unchanged by TNF-α-blocking agents. CONCLUSION: Neither ADA nor ETA modified the percentages or absolute numbers of circulating CD4+CD25hi Tregs and their phenotypes after being administered for 6 and 12 weeks to RA patients. TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00234234.
23253630 Ultrasound imaging for the rheumatologist. XLII. Assessment of hip pain in rheumatic patie 2012 Nov Hip pain is a common complaint in daily practice and the identification of the underlying pathologic condition is the first step for an adequate treatment. In this review, we discuss the available evidence for the application of conventional radiography, computed tomography and magnetic resonance imaging in rheumatologic patients with painful hip, presenting the main imaging findings due to osteoarthritis, inflammatory arthritis (rheumatoid arthritis and spondyloarthritides), osteonecrosis and some other soft tissue involvement (bursitis and synovial cyst) that could be the cause of hip pain. Because different imaging techniques show different sensitivity and specificity, the choice of technique to use depends on the type and stage of the disease itself.
22035626 Subclinical atherosclerosis and endothelial dysfunction in patients with early rheumatoid 2012 Apr OBJECTIVE: In this study, we aimed to investigate the frequency of endothelial dysfunction and subclinical atherosclerosis in early rheumatoid arthritis (RA) patients by carotid intima-media thickness (cIMT) and endothelial-dependent flow mediated vasodilatation (ED-FMD) as compared with healthy controls. METHODS: The study included 35 early RA patients (disease duration <12 months) and 35 healthy controls. Intima-media thickness of common carotid artery and ED-FMD of brachial artery were measured by high-resolution ultrasonography. Disease activity of RA was assessed by Disease Activity Score and activities of daily living were determined by Health Assessment Questionnaire-Disability Index Score. RESULTS: RA patients (age 38.3 ± 10.6 years) had average disease duration of 0.46 ± 0.28 years and 22 patients (62.9%) were rheumatoid factor (RF) positive (RF titer >9.56 IU/mL). There were no significant differences between age, sex, and lipid profiles of patient and control group. cIMT was significantly higher in RA patients (0.50 ± 0.16 mm) than in controls (0.44 ± 0.09 mm) (P = 0.007). Similarly, FMD% was significantly lower in RA patients [5.26 (2.9-10.6)] as compared with controls [10.34 (7.4-14.3)] (P = 0.004). Age, systolic blood pressure, tender joint count, and swollen joint count had significant correlations with patient cIMT. RF titer came out to be the major risk factor for increased cIMT of the patients. CONCLUSIONS: Compared with controls, early RA patients have higher cIMT and lower FMD%, denoting premature atherosclerosis. Our data suggest that early determination of FMD% and cIMT may be useful tools to assess cardiovascular risk even in early RA patients.
21607558 Sonographic assessment of carpal tunnel syndrome in rheumatoid arthritis: prevalence and c 2012 Aug Carpal tunnel syndrome (CTS) is one of the most frequent extra-articular manifestations of rheumatoid arthritis (RA). High frequency ultrasonography (US) is a sensitive and specific method in diagnosis of CTS. This study is aimed to: firstly assess diameter frequency of CTS in RA with US and compare with a control group; secondly, investigate relationship of CTS with disease activity. One hundred consecutive RA patients (women/men: 78/22) fulfilling ACR 1987 RA criteria and 45 healthy controls (women/control: 34/11) were enrolled into study. Disease activity parameters, RA and CTS patient global assessment and health assessment questionnaire (HAQ-DI) were recorded. Both patient and control group were questioned about secondary causes of CTS, and Katz hand diagram, Boston CTS questionnaire and Phalen ve Tinel tests were applied once for each hand. Wrist joint and carpal tunnel were assessed with US grey scale and power Doppler US, then cross-sectional area of median nerve (CSA) was calculated. Patients with median nerve CSA between 10.0 and 13.0 mm(2) were evaluated with electromyography (EMG). CTS was diagnosed if CSA of median nerve >13.0 mm(2) or CTS was shown with NCS. Although there was no difference between RA patients and controls in age, sex, history of DM (+) and goitre, CTS was more frequent in RA group (respectively, 17.0% vs. 4.4%, P = 0.038). In RA group with CTS, age, history of DM, disease duration, HAQ-DI score, CTS patient global score, Boston symptom severity and functional status scores were elevated compared to without CTS [respectively, 57 (36-73) vs. 50 (24-76), P = 0.041; 35.3% vs. 6.0%, P < 0.001; 108 (12-396) months vs. 72 (6-360) months, P = 0.036; 1.93 (0.75-2.87) vs. 1.125 (0-2.75), P = 0.013; 52 (1-97) vs. 25 (0-91), P = 0.001; 2.81 (1.18-4.17) vs. 2.0 (1.0-4.01), P = 0.01; 3.37 (1.37-5.0) vs. 2.25 (1.0-5.0), P = 0.008]. No difference was found between CTS (+) and (-) RA patients in acute phase reactants, disease activity and US findings (P > 0.05). Sensitivity of Katz hand diagram was higher than Tinel and Phalen tests (respectively, 100, 60.0, 66.7%). Boston symptom and functional scores of RA patients with CTS diagnosed by EMG were increased than patients CTS (-) by EMG [respectively, 3.05 (1.90-4.27) vs. 1.55 (1.0-2.90), P = 0.002; 3.25 (1.73-3.82) vs. 1.12 (1.0-2.10), P = 0.008]. CTS frequency in RA was found higher than normal population, especially in patients with additional risk factors of CTS. There was no relationship between CTS and disease activity. CTS group had long disease duration and worse functional status. CTS could be a result of the chronic course in RA. In patient with CSA between 10 and 13 mm(2), Boston CTS questionnaire might give additional idea about CTS.
20299184 Long-term survivorship analysis of the cementless Spotorno femoral component in patients l 2011 Apr The long-term survival of the cementless Spotorno (CLS) femoral component (Zimmer Inc, Warsaw, USA) was evaluated in a consecutive series of 85 patients (100 hips) less than 50 years of age. The mean follow-up was 12.3 years. Two patients (3 hips) were lost to follow-up, and 3 (4 hips) died. The survival rate of the CLS stem was 96.9% (confidence interval [CI], 93.6%-100%) after 13 years based on revision of the stem for any reason. The survival of the stem with revision for aseptic loosening as the end point was 97.9% (CI, 95.1%-100%) at 13 years. The mean Harris hip score at time of follow-up was 94. The long-term survival of the CLS stem is excellent in patients less than 50 years of age.
22942327 The efficacy and safety of muscle relaxants in inflammatory arthritis: a Cochrane systemat 2012 Sep OBJECTIVE: To determine the efficacy and safety of muscle relaxants in pain management in patients with inflammatory arthritis (IA). METHODS: We searched the Cochrane Central Register of Controlled Trials, Medline, Embase, and PsychINFO for randomized controlled trials in adults with IA that compared any muscle relaxant (administered via any route) to another analgesic intervention or placebo. We also searched the 2008-2009 American College of Rheumatology and European League Against Rheumatism abstracts and performed a hand search of reference lists of relevant articles. Primary outcomes were patient-reported pain relief ≥ 30% and withdrawals due to adverse events. Two authors independently assessed methodological quality and extracted data. RESULTS: Six trials (126 participants) were included in this review. All trials were deemed to have a high risk of bias. Five crossover trials evaluated benzodiazepine; 4 assessed diazepam (n = 71), and one assessed triazolam (n = 15). The sixth trial, a parallel-group study, evaluated zopiclone (non-benzodiazepine, n = 40). No trial was longer than 2 weeks and 3 single-dose trials assessed outcomes at 24 hours only. Overall, the included trials failed to find evidence of a beneficial effect of muscle relaxants over placebo (at 24 hours, 1 week, or 2 weeks) or in addition to nonsteroidal antiiflammatory drugs (at 24 hours) on pain intensity, function, or quality of life. Data from 2 trials of longer than 24-hour duration (diazepam and zopiclone, n = 74) found that participants who received a muscle relaxant had significantly more adverse events compared with those who received placebo [number needed to harm (NNTH) 3, 95% CI 2 to 7]. These were predominantly central nervous system side effects including dizziness and drowsiness (NNTH 3, 95% CI 2 to 11). CONCLUSION: Based upon the currently available evidence in patients with IA, benzodiazepines (diazepam and triazolam) do not appear to be beneficial in improving pain over 24 hours or 1 week. The non-benzodiazepine agent zopiclone also did not significantly reduce pain over 2 weeks. However, even short-term muscle relaxant use (24 hours to 2 weeks) is associated with significant adverse events, predominantly drowsiness and dizziness.
21866934 Clickable enzyme-linked immunosorbent assay. 2011 Oct 10 Click chemistry is explored as a potential cost-effective and selective immobilization method for the production of an enzyme-linked immunosorbent assay (ELISA). Coatings were formulated containing either a terminal alkyne or a bicyclo[6.1.0]non-4-yne (BCN) chemical handle, and a diagnostic peptide was subsequently immobilized onto these coatings by the copper-catalyzed azide-alkyne 1,3-dipolar cycloaddition (CuAAC) or copper-free strain-promoted azide-alkyne 1,3-dipolar cycloaddition (SPAAC), respectively. The terminal alkyne-containing coating showed high background levels in subsequent ELISA's due to the copper catalyst used in the immobilization step. The BCN-containing coating, however, was successfully employed and presents a cost-effective alternative to existing (strept)avidin-biotin immobilization methods. This technology was illustrated with an ELISA used for the diagnosis of rheumatoid arthritis (RA) but could be easily applied to a wide range of diagnostic tests.
21530276 Synthesis and biological evaluation of unique stereodimers of sinomenine analogues as pote 2011 May 15 Inhibition of the excessive NO production has been recognized as a potential means for the treatment of rheumatoid arthritis (RA). In order to discover more potent inhibitors and explore the preliminary structure activity relationship, a series of unique stereodimers of sinomenine analogues were designed and synthesized. Their inhibitory activity on NO production and cytotoxicity were evaluated using LPS-activated murine macrophages RAW264.7 assay and MTT method, respectively. Among these compounds, 1a, 2, 2a, 2b, and 4 showed potent inhibitory activity on NO production without obvious cytotoxicity. Furthermore, 2, 2a, and 2b significantly suppressed mRNA expression of iNOS. Interestingly, (S)-dimers displayed a better bioactivity than (R)-dimers. These compounds may sever as lead candidates in the development of novel therapeutic drugs for RA treatment.
22999907 Two cases of Takayasu's arteritis occurring under anti-TNF therapy. 2013 Mar Takayasu's arteritis is a granulomatous, large vessel vasculitis that affects the aorta, its major branches and the pulmonary arteries. Compelling evidence exists to support the notion that Takayasu's arteritis is a T-cell mediated process and that tumor necrosis factor alpha (TNFa) is an important factor in the pathogenesis of this disease. Moreover, encouraging results from recent studies support the use of anti-TNFa therapy for relapsing or resistant cases of Takayasu's arteritis. Here, however, we describe the case of two patients: one with seropositive rheumatoid arthritis, the other with HLA-B27 negative spondylarthropathy, who developed Takayasu's arteritis during treatment with TNFa inhibitors (adalimumab and golimumab respectively). This is the first report of Takayasu's arteritis in rheumatic patients under TNFa blocking agents which suggests the presence of different pathogenetic mechanism in a subgroup of patients with Takayasu's arteritis, as well as a potential role of TNFa blockers as triggers of this disease in some cases.
22351532 Extensor tendon rupture in rheumatoid arthritis: a survey of patients between 2005 and 201 2012 BACKGROUND: Recent medical advancements in the treatment of rheumatoid arthritis (RA) can prevent joint damage and tendon involvement. The authors evaluated patterns of extensor tendon ruptures in RA patients that presented to hand surgeons over a recent five-year period. METHODS: Medical records and radiographs were retrospectively reviewed, and telephone interviews were conducted with 38 patients that had experienced extensor tendon ruptures in a rheumatoid hand during the study period and were operated on at one of five tertiary referral hospitals in South Korea. Patterns of tendon ruptures were compared in patients that did or did not receive medical treatment. RESULTS: Twenty-nine of the 38 patients (76%) had tendon ruptures in more than two digits. When multiple digits were involved, mean duration between first and latest rupture was 2.9 months. When patients treated with medications by rheumatologists (24 patients) were compared with those not treated (14 patients), no significant differences were found for; number of ruptured tendons, time from first to last rupture, disease duration, or radiographic RA severity. CONCLUSIONS: RA patients who once experienced a tendon rupture are still at risk of sequential tendon ruptures despite recent advancement of medical treatment. Education of the risks of sequential tendon ruptures and timely consultation to hand surgeons continue to be necessary in RA patients.
23121884 Investigation of Caucasian rheumatoid arthritis susceptibility loci in African patients wi 2012 Nov 3 INTRODUCTION: The largest genetic risk to develop rheumatoid arthritis (RA) arises from a group of alleles of the HLA DRB1 locus ('shared epitope', SE). Over 30 non-HLA single nucleotide polymorphisms (SNPs) predisposing to disease have been identified in Caucasians, but they have never been investigated in West/Central Africa. We previously reported a lower prevalence of the SE in RA patients in Cameroon compared to European patients and aimed in the present study to investigate the contribution of Caucasian non-HLA RA SNPs to disease susceptibility in Black Africans. METHODS: RA cases and controls from Cameroon were genotyped for Caucasian RA susceptibility SNPs using Sequenom MassArray technology. Genotype data were also available for 5024 UK cases and 4281 UK controls and for 119 Yoruba individuals in Ibadan, Nigeria (YRI, HapMap). A Caucasian aggregate genetic-risk score (GRS) was calculated as the sum of the weighted risk-allele counts. RESULTS: After genotyping quality control procedures were performed, data on 28 Caucasian non-HLA susceptibility SNPs were available in 43 Cameroonian RA cases and 44 controls. The minor allele frequencies (MAF) were tightly correlated between Cameroonian controls and YRI individuals (correlation coefficient 93.8%, p = 1.7E-13), and they were pooled together. There was no correlation between MAF of UK and African controls; 13 markers differed by more than 20%. The MAF for markers at PTPN22, IL2RA, FCGR2A and IL2/IL21 was below 2% in Africans. The GRS showed a strong association with RA in the UK. However, the GRS did not predict RA in Africans (OR = 0.71, 95% CI 0.29 - 1.74, p = 0.456). Random sampling from the UK cohort showed that this difference in association is unlikely to be explained by small sample size or chance, but is statistically significant with p<0.001. CONCLUSIONS: The MAFs of non-HLA Caucasian RA susceptibility SNPs are different between Caucasians and Africans, and several polymorphisms are barely detectable in West/Central Africa. The genetic risk of developing RA conferred by a set of 28 Caucasian susceptibility SNPs is significantly different between the UK and Africa with p<0.001. Taken together, these observations strengthen the hypothesis that the genetic architecture of RA susceptibility is different in different ethnic backgrounds.
22354869 Familial clustering of the serum cytokine profile in the relatives of rheumatoid arthritis 2012 Jun OBJECTIVE: Rheumatoid arthritis (RA) is prevalent in North American Native populations, with a high frequency of multicase families and seropositivity in first-degree relatives. This study was undertaken to determine whether the serum cytokine profile of first-degree relatives of North American Native patients with RA differed from that of individuals with no family history of autoimmunity and whether there was an association with RA autoantibodies. METHODS: North American Native patients with RA (n = 105), their first-degree relatives (n = 273), healthy North American Native controls (n = 200), and Caucasian controls (n = 150) were studied. Serum levels of 42 cytokines were tested using a multiplex laser bead assay. Rheumatoid factor (RF), anti-cyclic citrullinated peptide 2 (anti-CCP-2), monocyte chemotactic protein 1 (MCP-l), and high-sensitivity C-reactive protein (hsCRP) were tested by enzyme-linked immunosorbent assay, and HLA-DRB1 alleles by specific primers. Discriminant analysis and logistic regression classified individuals based on their cytokine profile. RESULTS: The prevalence of RF (cutoff level predetermined to include 5% of Caucasian controls) and anti-CCP (cutoff level of ≥40 units) was, respectively, 88% and 81% in the RA patients, 34% and 9% in first-degree relatives, and 9% and 4% in North American Native controls; the prevalence of anti-CCP was 0% in Caucasian controls. Levels of most cytokines were highest in RA patients; 17 of 40 cytokines (43%) were significantly higher in first-degree relatives than in controls, including multiple proinflammatory cytokines. Discriminant analysis showed a notable distinction between the groups, with 85% classification accuracy. First-degree relatives had markedly higher MCP-1 and hsCRP levels than North American Native controls, but there was no consistent association with RA autoantibodies. CONCLUSION: Our findings indicate that levels of multiple cytokines and hsCRP are higher in first-degree relatives of North American Native patients with RA compared to individuals from a nonautoimmune background. These data suggest that elevated baseline cytokine levels may be part of the risk profile for developing RA.
23087184 Why the findings of published multiple treatment comparison meta-analyses of biologic trea 2013 Sep 1 OBJECTIVES: To evaluate the quality of published multiple treatment comparison (MTC) meta-analyses on biologic disease modifying antirheumatic drugs (bDMARDs) for rheumatoid arthritis (RA), and to identify methodological issues that can explain the discrepancies in the findings of these MTCs. METHODS: We searched MEDLINE for MTCs of bDMARDs for RA. Following the PRISMA guidelines, we extracted a large set of methodological items. These comprised of inclusion/exclusion criteria, information sources, reported results and outcomes measures, approaches to dealing with differing response profiles to available treatments, monotherapies versus combination therapies, and potential sources of heterogeneity. RESULTS: We identified 13 published MTCs, of which nine were published since 2009. Despite similar stated eligibility criteria and objectives across MTCs, we identified major discrepancies in the estimated treatment effects, the inclusion of trials and analytic approaches. The number of included trials was typically much smaller than the number of eligible trials at the time of publication. Three out of six MTCs including patients of differing response profiles inappropriately combined DMARD-naive and DMARD-inadequate responder patients in the analyses. Four out of eight MTCs that considered both monotherapy and combination therapy (ie, concomitant DMARD) did not adjust for the potential effect modification. Half of the identified MTCs did not explore potential sources of heterogeneity, and the explored sources varied considerably. Last, most MTCs only included one or two efficacy outcomes (eg, ACR50) and only two considered health related quality of life outcomes (eg, HAQ). CONCLUSIONS: The identified methodological shortcomings and inconsistencies most likely explain the observed discrepancies in findings across MTCs.
21850473 Connective tissue growth factor, a regulator related with 10-hydroxy-2-decenoic acid down- 2012 Sep 10-hydroxy-2-decenoic acid (10H2DA) is suggested to be a potential medication for rheumatoid arthritis (RA) by activation of matrix metalloproteinases (MMPs) via mitogen-activated protein kinase signaling pathways. The aim of the present work was to seek differentially expressed proteins in rheumatoid arthritis synovial fibroblasts (RASFs) treated with 10H2DA by comparative proteomics analysis. Two-dimensional electrophoresis (2-DE) and LC-MS/MS were performed to identify changes in protein expression after 24-h 10H2DA treatment. Differentially expressed proteins were identified by real-time PCR and Western blot analysis. Influence of down-regulation of connective tissue growth factor (CTGF) expression on MMPs was studied by RNAi. Ten proteins were up-regulated and 9 proteins were down-regulated after 24-h 10H2DA treatment. A total of 19 differentially expressed proteins were identified and found to be associated with glycolysis, lipid metabolism, cell adhesion, ATP synthesis, oxidation reduction, and anti-apoptosis. CTGF, a member of the C-terminal cystein-rich proteins (CCN) family, was down-regulated after 24-h 10H2DA treatment. MMPs were down-regulated after RNAi (CTGFi). These results suggest that CTGF is a regulator factor in the expression of MMPs, and 10H2DA down-regulate the concentration of MMPs probably by down-regulating the expression of CTGF.
23149338 Progranulin antibodies in autoimmune diseases. 2013 May Systemic vasculitides constitute a heterogeneous group of diseases. Autoimmunity mediated by B lymphocytes and their humoral effector mechanisms play a major role in ANCA-associated vasculitis (AAV) as well as in non-ANCA associated primary systemic vasculitides and in the different types of autoimmune connective tissue disorders and rheumatoid arthritis. In order to detect autoantibodies in systemic vasculitides, we screened protein macroarrays of human cDNA expression libraries with sera from patients with ANCA-associated and ANCA-negative primary systemic vasculitides. This approach led to the identification of antibodies against progranulin, a 88 kDA secreted glycoprotein with strong anti-inflammatory activity in the course of disease of giant-cell arteritis/polymyalgia rheumatica (14/65), Takayasu's arteritis (4/13), classical panarteritis nodosa (4/10), Behcet's disease (2/6) and in the course of disease in granulomatosis with polyangiitis (31/75), Churg-Strauss syndrome (7/23) and in microscopic polyangiitis (7/19). In extended screenings the progranulin antibodies were also detected in other autoimmune diseases such as systemic lupus erythematosus (39/91) and rheumatoid arthritis (16/44). Progranulin antibodies were detected only in 1 of 97 healthy controls. Anti-progranulin positive patients with systemic vasculitides, systemic lupus erythematosus or rheumatoid arthritis had significant lower progranulin plasma levels, indicating a neutralizing effect. In light of the anti-inflammatory effects of progranulin, progranulin antibodies might exert pro-inflammatory effects thus contributing to the pathogenesis of the respective autoimmune diseases and might serve as a marker for disease activity. This hypothesis is supported by the fact that a positive progranulin antibody status was associated with active disease in granulomatosis with polyangiitis.
21504398 Immunological risk factors for infection after immunosuppressive and biologic therapies. 2011 Apr Immunosuppressive and biologic therapies are costly and can involve a considerable risk of infection. Noninvasive diagnostic tools for early prediction of infection before and after administration of these therapies are of major interest. Serial longitudinal immune monitoring would provide data on immunocompetence and complement clinical follow-up protocols. Biomarkers of immune response may be useful to identify patients at risk of developing infection and who could be candidates for immunosuppressant dose reduction. This article focuses on the potential use of biomarkers of immune response to predict development of infection after immunosuppressive and biologic therapies in selected settings of autoimmune disease (rituximab for treatment of rheumatoid arthritis) and solid organ transplantation.