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ID PMID Title PublicationDate abstract
22922428 PLGA microspheres encapsulating siRNA anti-TNFalpha: efficient RNAi-mediated treatment of 2012 Nov The aim of this study was to investigate potentialities of poly(dl-lactide-co-glycolide) (PLGA) microspheres for the delivery of small interfering RNAs (siRNAs) against tumor necrosis factor α (TNF-α) to achieve prolonged and efficient inhibition of TNF-α for the treatment of rheumatoid arthritis (RA). PLGA microspheres were prepared by a modified multiple emulsion-solvent evaporation method. The formulations were characterized in terms of morphology, mean diameter and siRNAs distribution, encapsulation efficiency, and in vitro release kinetics. The efficiency of this system was then evaluated both in vitro and in vivo using the murine monocytic cell line J774 and a pre-clinical model of RA, respectively. siRNA-encapsulating PLGA microspheres were characterized by a high encapsulation efficiency and a slow and prolonged anti-TNF-α siRNAs. Our results provide evidence that, upon intra-articular administration, PLGA microspheres slowly releasing siRNAs effectively inhibited the expression of TNF-α in arthritic joints. Our system might represent an alternative strategy for the design of novel anti-rheumatic therapies based on the use of RNA interference in RA.
21619619 Comparisons of 7- to 78-joint ultrasonography scores: all different joint combinations sho 2011 May 27 INTRODUCTION: The primary objectives were to explore the associations between a comprehensive ultrasonographic (US) assessment of joints, tendons and bursae and previously described reduced joint counts (7-, 12-, 28- and 44-joint score) as well as to assess the sensitivity to change of these different US joint combinations during biological treatment. METHODS: Twenty patients with rheumatoid arthritis (RA) were examined by US (B-mode (BM) and power Doppler (PD)) with use of a semi-quantitative (0 to 3) score of 78 joints, 36 tendons/tendon groups and two bursae (hereafter described as the 78-joint score) at baseline and 1, 3, 6 and 12 months after initiating treatment with adalimumab. BM and PD scores for the different joint combinations were generated. RESULTS: The reduced joint scores had high correlation coefficients with the 78-joint score at all examinations (range 0.79 to 0.99 for BM and 0.77 to 0.99 for PD, each P < 0.001) and sum BM and PD scores of all the different joint combinations improved significantly during follow-up (P ≤ 0.05 to 0.001). CONCLUSIONS: The reduced joint combinations were highly associated to the 78-joint score. Furthermore, all the joint combinations presently explored responded well to biological treatment. This indicates that an approach focusing on few joints and tendons gives equivalent information about the inflammatory activity in RA patients as a comprehensive US examination. The optimal combination of joints and tendons for a valid, reliable and feasible US measurement should be further explored to define a US score for follow-up of RA patients on biological treatment.
22065075 A case of leukoencephalopathy associated with adalimumab-treated rheumatoid arthritis and 2012 Nov Tumor necrosis factor-alpha (TNF-alpha) inhibitor is recently being widely used to treat autoimmune diseases, but some noticeable adverse events were reported and neurological events have especially been described. It is mandatory to compare these cases for finding the risk factors, the duration of the neurological events, their processes and their outcomes. We present here the case of leukoencephalopathy secondary to adalimumab, which is a tumor necrosis factor α (TNF-α) inhibitor. We also reviewed the other 14 published leukoencephalopathy cases associated with the use of TNF inhibitors. Eleven patients had underlying rheumatoid arthritis, and the others had psoriatic arthritis, ankylosing spondylitis and Still's disease. The median duration of treatment with anti-TNF-α before the presentation of neurological symptoms was 9.2 months (range: 1.5-24). The duration of using anti-TNF-α was not related with the outcome. Although cases of neurological adverse events associated with anti-TNF-α treatment are rare, it is very important to monitor the neurological signs and symptoms suggestive of a demyelinating disorder in RA patients who are receiving anti-TNF-α treatment and especially those patients who are older and who have a history of MS or demyelination.
22806369 Muscle characteristics in patients with chronic systemic inflammation. 2012 Aug INTRODUCTION: Histological characteristics of age-related muscle wasting are type II muscle fiber atrophy, accumulation of oxidative stress-induced lipofuscin granules and decreased satellite cell numbers. There is increasing clinical evidence for a strong correlation between chronic systemic inflammation and age-related muscle wasting. The aim of this study was to determine the impact of chronic systemic inflammation on age-related histological muscle characteristics. METHODS: As a model for chronic systemic inflammation, we included 10 patients suffering from rheumatoid arthritis (RA) and 27 control patients suffering from osteoarthritis (OA). Biopsies were taken from the vastus medialis muscle. RESULTS: No significant differences were found in type II muscle fiber atrophy, lipofuscin accumulation, or satellite cell number in RA compared with OA patients. CONCLUSIONS: These results suggest there is no association between chronic systemic inflammation in RA and age-related muscle characteristics. Future research should focus on inflammation and satellite cell function.
21865281 Risk of infections in rheumatoid arthritis patients treated with tocilizumab. 2012 May OBJECTIVES: To investigate the occurrence and risk factors for infections in RA patients treated with tocilizumab. METHODS: A cohort of all RA patients (n = 112) starting tocilizumab therapy between October 2008 and March 2010 in Northern Bavaria was screened for infections. Mild/moderate and severe infections were recorded. Multivariate logistic regression analysis was used to define risk factors for infection. RESULTS: Overall, 26 patients developed infections [23.2%; 58.0/100 patient-years (py)], 18 of them were mild to moderate (16.1%, 40.1/100 py) and 8 were severe (17.9/100 py). Concomitant use of LEF and prednisone, high disease activity and previous therapy with rituximab were associated with the occurrence of mild/moderate infections. Severe infections were related to longer disease duration, exposure to more than three previous DMARDs and concomitant therapy with proton-pump inhibitors. CONCLUSION: The rate of infection in RA patients treated with tocilizumab in clinical practice is higher than in the clinical trial populations. Increased attention should especially be given to patients with longer disease duration, previous exposure to multiple DMARDs, i.e. previous exposure to rituximab and those receiving concomitant LEF, prednisone or proton-pump inhibitor treatment.
23021157 Prevalence of calcium pyrophosphate and monosodium urate crystals in synovial fluid of pat 2013 May OBJECTIVE: The main aim of this study was to investigate the frequency of monosodium urate (MSU) and calcium pyrophosphate (CPP) crystals in synovial fluid (SF) obtained from patients with previously diagnosed joint diseases. METHODS: We reviewed the results of SF analysis of 5020 samples identifying those collected from patients with a previously definite diagnosis (2370 samples). SF analysis results, age, sex, diagnosis and disease duration were recorded from computerized records of patients' archives. RESULTS: The prevalence of CPP crystals in SF was 22.28% in osteoarthritis (OA), 8.28% in rheumatoid arthritis (RA), 3.82% in psoriatic arthritis (PsA), 2.79% in other spondyloarthropathies (SpA), 10% in septic arthritis (SeA), 0.66% in gout and 9.18% in the miscellanea of joint diseases, respectively. The prevalence of MSU crystals in SF was 0.30% in RA, 3.34% in PsA, 0.70% in other SpA, 0.80% in acute CPP crystal arthritis (CPP-CA), 0% in OA, reactive arthritis (ReA), SeA, juvenile idiopathic arthritis (JIA) and miscellanea. In OA group, we observed that age and SF inflammatory indices were higher in SF positive to CPP crystals with respect to those without crystals (P<0.0001). In RA, we found that the group of patients with CPP crystals was significantly older (P=0.001) and had a SF less inflammatory (P=0.022) with respect to that without crystals but with a higher disease duration than those without crystals. CONCLUSION: Crystals can be detected more frequently than expected in SF from joint diseases with a previous established diagnosis. This highlights the importance of SF analysis for the diagnosis of possible comorbidities linked to the presence of crystals.
20737187 The short-term outcome of the modified Sauvé-Kapandji procedure regarding range of motion 2011 Feb The Sauvé-Kapandji (S-K) procedure is a common treatment for rheumatoid wrists, but in some cases severe bone destruction makes this operative modality difficult to perform, while also resulting in a poor outcome. A modified S-K procedure for these wrists has been reported, but the clinical outcomes of the modified procedure are unclear. This study evaluated 24 wrists in 20 patients who underwent the modified S-K procedure. The mean follow-up period was 34.5 months. The clinical assessments were range of motion, carpal bone translation and bony shelf size. The range of motion and carpal bone translation were similar to those produced by the S-K procedure. In regard to bony shelf size, wrists with an excessively large bony shelf tended to have a progression of carpal bone translation toward the palmar direction due to the residual malposition of the ECU tendon. The modified S-K procedure appears to be a safe and effective surgical alternative for the treatment of severely destroyed rheumatoid wrists. Although the modified procedure allows for the adjustment of the bony shelf size, it should not be used with wrists that have an excessively large bony shelf.
21452295 Favorable effect of very early disease-modifying antirheumatic drug treatment on radiograp 2011 Jul OBJECTIVE: While there is consensus that treatment with disease-modifying antirheumatic drugs (DMARDs) should be started early in patients with inflammatory arthritis, confirmation that radiographic progression is inhibited with early treatment start is scarce. This study was undertaken to compare radiographic progression in patients treated with a DMARD very early in the course of their disease (within 3 months of diagnosis) and those who began DMARD treatment later. METHODS: Patients included in the French observational ESPOIR (Étude et Suivi des Polyarthrites Indifférenciées Récentes [Study and Followup of Early Undifferentiated Polyarthritis]) cohort were followed up, and radiographic progression after 12 months was assessed. Propensity scores, reflecting the indication to start a DMARD, were obtained by modeling the start of DMARD therapy by disease-specific and demographic variables obtained at baseline, using logistic regression analysis. The influence of very early versus delayed DMARD start on radiographic progression was evaluated by generalized linear regression, with and without adjustment for propensity scores. RESULTS: Six hundred sixty-one patients were analyzed. In an unadjusted analysis, patients starting DMARD therapy within 3 months of diagnosis did not show a significant difference in radiographic progression score as compared to those starting DMARD therapy later (1.2 units versus 1.6 units; P = 0.37). Adjustment for the propensity score revealed a statistically significant difference in mean progression (0.8 units versus 1.7 units; P = 0.033). Analysis by propensity score quintile showed a trend suggesting that early treatment was especially beneficial for patients in the fourth and fifth quintiles (worse prognosis). CONCLUSION: Our findings indicate that among patients with inflammatory arthritis in daily clinical practice, early initiation of DMARD therapy reduces 12-month radiographic progression. This strengthens the current recommendations for very early initiation of specific therapy in patients with early arthritis.
21515601 Pneumococcal antibody levels after pneumovax in patients with rheumatoid arthritis on meth 2011 Jul INTRODUCTION: Immunisation against pneumococcus has been shown to reduce pneumonia in rheumatoid arthritis (RA). There is concern that methotrexate may reduce its efficacy. There are very few objective data on the effect of methotrexate on the efficacy of pneumococcal vaccination with pneumovax, and no objective evidence on whether revaccination is necessary in RA patients on methotrexate. METHODS: The authors collected information from 180 RA patients on methotrexate relating to their vaccination status and assayed their pneumococcal antibody levels. Data on pulmonary infection were retrieved in the same patients over the preceding decade. RESULTS: Full data were available for 152 patients, of whom 28 had never been vaccinated against pneumococcus. Median levels were significantly higher in those who had been vaccinated. Unvaccinated patients and those taking oral prednisone were more likely to have had pneumonia in the previous 10 years. The RR for developing pneumonia among non-vaccinated patients was 9.7 (p=0.005) and among steroid-treated patients was 6.5 (p=0.001), after adjusting for age, gender, disease duration and comorbidity. No significant correlation was found between pneumococcal antibody levels and time since vaccination. CONCLUSIONS: This study suggests that a single administration of pneumovax early in RA offers up to 10 years protection against the development of pneumococcal pneumonia in RA patients on methotrexate.
21082209 Serodiagnosis of Mycobacterium avium-complex pulmonary disease with an enzyme immunoassay 2011 Apr Rheumatoid arthritis (RA) has many pulmonary manifestations, including bronchial abnormalities that can develop into Mycobacterium avium-complex (MAC) pulmonary disease (PD). MAC-PD can be lethal in patients receiving tumor necrosis factor-alpha blockers despite administration of antibiotics. Diagnosis of MAC-PD is often difficult, because MAC is an environmental organism. In this study, we investigated the usefulness of serodiagnosis of MAC-PD in RA patients by using an enzyme immunoassay (EIA) kit that detects anti-glycopeptidolipid (GPL) core antigen IgA antibodies. Antibody levels were measured in 63 patients with RA: 14 with MAC-PD plus 3 cultured nontuberculous mycobacteria (NTM) other than MAC, 16 with pulmonary abnormalities characterizing NTM but undetected in sputum culture, and 30 control subjects. RA patients with MAC-PD showed significantly higher antibody levels than controls (p = 0.02). The cutoff point was set at 0.7 IU/l, making the sensitivity and specificity of the antibody in MAC-PD and control patients 43% and 100%, respectively. The EIA kit is useful for diagnosis of MAC-PD in RA patients because of its high specificity. This test is an easier and less invasive form of examination and could therefore replace bronchoscopy as the main diagnostic procedure for RA patients with MAC-PD.
22206446 Patient-reported outcome after rheumatoid arthritis-related surgery in the lower extremiti 2012 Apr BACKGROUND AND PURPOSE: Although decreasing with the development of effective pharmacological regimes, joint surgery has improved the function and quality of life of patients with rheumatoid arthritis (RA). Few studies have assessed patient-reported outcomes after RA surgery to the lower extremities. Here we report patient-relevant outcome after RA-related surgery based on the first data from the Swedish National Register of Rheuma Surgery (RAKIR). PATIENTS AND METHODS: 258 RA patients (212 women) who had joint surgery performed at the Department of Orthopaedics, Spenshult Hospital between September 2007 and June 2009 were included. Mean age at surgery was 64 (20-86) years. The patients completed the SF-36 and HAQ questionnaires preoperatively and 6 months postoperatively, and 165 patients completed them after 12 months. RESULTS: Improvement was seen as early as at 6 months. At 12 months, 165 patients (141 women)-including hip (n = 15), knee (n = 27), foot (n = 102), and ankle (n = 21) patients-reported statistically significant improvements from preoperatively to 12 months postoperatively in HAQ (mean change: -0.11) and SF-36 subscales physical function (11), role physical (12), bodily pain (13), social functioning (6.4), and role emotional (9.4). Hip and knee patients reported the greatest improvements. INTERPRETATION: Orthopedic RA-related surgery of the lower extremities has a strong effect on pain and physical function. Improvement is evident as early as 6 months postoperatively and remains after 12 months.
21284495 A marked decline in the incidence of renal replacement therapy for amyloidosis associated 2011 Mar Risk for amyloidosis in rheumatic diseases is associated with a long-lasting inflammation. To assess possible changes in the incidence of terminal uraemia due to amyloidosis associated with rheumatic diseases on a nationwide basis, we scrutinised the files of the Finnish Registry for Kidney Diseases for patients suffering from amyloidosis associated with rheumatoid arthritis (RA), ankylosing spondylitis (AS) or juvenile idiopathic arthritis (JIA) over the period 1995-2008. The registry has an estimated 97-99% coverage of all patients accepted for renal replacement therapy (RRT) in the country. Data on the consumption of antirheumatic drugs were collected from two sources: the Social Insurance Institution's Drug Reimbursement Register, and the Sales Register of the National Agency for Medicines from the above period. Altogether 264 cases were identified. Two hundred twenty-nine of them had RA, 15 AS and 20 JIA. When the total annual number of new admissions to RRT varied between 20 and 37 at the end of 1990s, it was under half of that from 2002 onwards. Over this period, the number of users of low-dose methotrexate (MTX) has increased 3.6-fold, the drug being the most frequently used disease modifying anti-rheumatic drug in Finland. The present nationwide series is the first to show that the incidence of end-stage renal disease due to amyloidosis associated with rheumatic diseases is decreasing. An obvious reason for this is intensive anti-rheumatic drug therapy.
23477160 [Short-term clinical observation on compound Xiatianwu combined with methotrexate in treat 2012 Dec OBJECTIVE: To observe the short-term clinical efficacy of compound Xiatianwu combined with methotrexate (MTX) in treating rheumatoid arthritis. METHOD: One hundred and four patients with rheumatoid arthritis were randomly divided into two groups: 64 cases in the combined treatment group who was treated with compound Xiatianwu combined with MTX, and the remaining 40 cases in the control group which was only treated with MTX. The changes in ACR20, ACR50, ACR70 and laboratory indexes including anti-cyclic citrulline polypeptide, rheumatoid factor, erythrocyte sedimentation rate, high sensitivity creative protein were compared before and after treatment. Adverse reactions in the two groups were observed as well. RESULT: After being treated for 3 months, the ACR20 improvement rate reached 59.4% in the combined treatment group, higher than 35% in the control group, with significant statistical difference (P <0.05); The ACR50 improvement rate reached 32. 8% the treated group, also higher than 17.5% in the control group, with significant statistical difference (P <0.05). After treatment for three months, both groups showed remarkable improvement in anti-cyclic citrulline polypeptide, rheumatoid factor, erythrocyte sedimentation rate and high sensitivity creative protein compared with that before treatment, demonstrating statistical significance (P <0. 05). The combined treatment group displayed more significant improvement in erythrocyte sedimentation rate and high sensitivity creative protein as well as much less adverse reactions than the MTX group. CONCLUSION: Compound Xiatianwu combined with MTX can effectively improve clinical symptoms of RA patients and laboratory indexes, and shows higher medication safety.
22986289 Traditional cardiovascular risk factors, inflammation and cardiovascular risk in rheumatoi 2013 Jan Multiple studies demonstrate an increased cardiovascular (CV) risk associated with RA compared with the general population. While part of this risk appears to be mediated by RA-specific factors, such as long-term inflammation, traditional CV comorbidities also play an important role. We review evidence from previous studies of the relationship between RA and traditional CV comorbidities such as dyslipidaemia, obesity, insulin resistance and diabetes, hypertension, cigarette smoking and physical inactivity. We examine the prevalence and consider the effect of inflammation and RA treatments on these risk factors. Finally, we discuss three widely used CV risk estimators, the Framingham Risk Score, Reynolds Risk Score and the Systematic Coronary Risk Evaluation, and their performance in patients with RA. The traditional CV risk factors that appear to differ significantly between RA cases and controls include insulin resistance, abnormal fat distribution, cigarette smoking and lack of physical activity. Dyslipidaemia, diabetes and hypertension may also be elevated in RA; however, the evidence is conflicting. Overall, we found that the majority of information regarding CV risk factors in RA stems from data collected as covariates for studies on CV disease. A gap in knowledge exists regarding detailed information on individual risk factors in RA, their prevalence and modifications that occur as a result of inflammation or treatment. More studies are needed to develop methods for accurate CV risk estimation in RA.
22075065 Correlation between computer-aided dynamic gadolinium-enhanced MRI assessment of inflammat 2012 Jan OBJECTIVE: To test the correlation between assessment of inflammation using dynamic contrast-enhanced MRI (DCE-MRI) analysed by a novel computer-aided approach and semi-quantitative scores of synovitis and bone marrow oedema (BME) using the OMERACT-RA MRI Scoring (RAMRIS) system, in the wrist of patients with RA. METHODS: Fifty-four RA patients had conventional and DCE-MRI of a symptomatic wrist using a low-field 0.2T extremity scanner. RAMRIS synovitis and BME of the wrist joint were done. DCE-MRI data were analysed in three ways: (i) in all images (fully automated approach), (ii) within a large extended region of interest (ROI) placed around the wrist joint (semi-automated approach) and (iii) within a small ROI placed in the area with most visual enhancement (semi-automated approach). Time spent on each procedure was noted. Spearman's rank correlation test was applied to assess the correlation between RAMRIS and the computer-generated dynamic parameters. RESULTS: RAMRIS synovitis (range 2-9), BME (range 0-39) and the dynamic parameters reflecting the number of enhancing voxels were significantly correlated, especially when an extended ROI around the wrist was used (ρ = 0.74; P < 0.01 for synovitis and ρ = 0.82; P < 0.01 for BME). The observer spent on average 20 min (range 12-25 min) to perform RAMRIS, including acquisition of the results in the database, and 8 min (range 7-10 min) to perform all above-mentioned computer-aided analyses. CONCLUSION: Computer-aided analysis of DCE-MRI data correlated with RAMRIS synovitis and BME and was twice as fast to perform. This technique may be useful for quick semi-automated assessment of joint inflammation, but needs further validation.
22843208 Cost per responder associated with biologic therapies for Crohn's disease, psoriasis, and 2012 Jul INTRODUCTION: Biologic therapies have demonstrated efficacy and safety in several chronic systemic disorders. The authors indirectly compared response rates and costs per responder associated with biologic treatments for moderate-to-severe Crohn's disease (CD), psoriasis (Ps), and/or rheumatoid arthritis (RA). METHODS: A systematic literature search was performed to identify phase 3 randomized controlled trials of biologics for CD (adalimumab, infliximab), Ps (adalimumab, etanercept, infliximab, ustekinumab 45 mg, ustekinumab 90 mg), or methotrexate-refractory RA (abatacept, adalimumab, certolizumab, etanercept, golimumab, infliximab, rituximab, tocilizumab). Food and Drug Administration-approved dosing schedules were evaluated. Published response rates were extracted, with response defined in CD, Ps, and RA as: ≥70-point reduction in CD Activity Index at 12 months; ≥75% improvement in Psoriasis Area and Severity Index at 3 months; and ≥50% improvement in American College of Rheumatology component scores at 6 months. Within each indication, mixed-treatment comparison meta-analyses were conducted to derive pooled estimates and 95% CIs of response rate difference versus placebo for each biologic, adjusting for cross-trial variation in control-arm response rates. Cost per responder was estimated for each biologic as projected per patient drug costs (2011 US$) divided by response rate difference. RESULTS: Altogether, 23 publications were selected. In CD, 12-month cost per responder was estimated at $116,291 (95% CI $71,637-208,348) for adalimumab and $125,169 (95% CI $60,532-267,101) for infliximab. Among biologics approved in Ps, 3-month cost per responder was lowest for adalimumab ($9,756; 95% CI $8,668-11,131), infliximab ($12,828; 95% CI $11,772-13,922), and ustekinumab 45 mg ($13,821; 95% CI $12,599-15,167). In RA, biologics with the lowest 6-month cost per responder were adalimumab ($27,853; 95% CI $19,284-40,270), etanercept ($29,140; 95% CI $14,170-61,030), and tocilizumab ($31,363; 95% CI $14,713-64,232). CONCLUSION: Meta-analyses of clinical trials found considerable variation in cost-effectiveness of biologic therapies for CD, Ps, and RA. These results may help determine biologic utilization in these chronic diseases.
21784722 Venous thrombotic events are not increased in patients with rheumatoid arthritis treated w 2011 Oct OBJECTIVES: Past studies have reported conflicting rates of venous thrombotic events (VTEs) in rheumatoid arthritis (RA). The current study aimed to compare (1) the rates of VTEs in patients with RA treated with anti-tumour necrosis factor (anti-TNF) therapy versus those treated with non-biological disease-modifying antirheumatic drugs (nbDMARDs) alone and (2) the rates between each individual anti-TNF agent and nbDMARDs. METHODS: Using data from the British Society for Rheumatology Biologics Register, a national prospective observational cohort study of biological safety in patients with RA, the authors compared the incidence of VTEs between 11 881 anti-TNF- and 3673 nbDMARD-treated patients. Analysis was limited to the first VTE per person. HRs were calculated using Cox modelling. Adjustment was made for potential confounders including surgery performed during follow-up. RESULTS: A total of 196 first VTEs were reported (151 anti-TNF, 45 nbDMARD). Overall there was no difference in the rates of VTEs between anti-TNF- and nbDMARD-treated patients (adjusted HR 0.8 (95% CI 0.5 to 1.5)). The risk was similar across all anti-TNF agents. Rates of postoperative VTEs did not significantly differ between groups. CONCLUSIONS: These data suggest that anti-TNF therapy is not associated with an increased risk of VTEs in RA patients.
21601309 Interaction between oxidative stress and chemokines: possible pathogenic role in systemic 2011 Sep Imbalance oxidative stress and chemokines are considered as a universal factors involved in the development of various clinical features seen in the patients with SLE and arthritis. To evaluate the interaction between oxidative stress and chemokines and their relationship with disease activity in SLE and RA patients, oxidative/anti-oxidant profiles and chemokines were assessed. Oxidant and anti-oxidant enzymes were measured in the plasma and the levels of chemokines; MCP-1/CCL2, RANTES/CCL5, MIP-1β/CCL-4 and IP-10/CXCL-10 were evaluated in the serum by an enzyme-linked immunosorbent assay (ELISA). A significant increase in the level of lipid peroxidation was found in SLE and RA patients and positively associated with disease activity. The activities of anti-oxidant enzymes: superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and anti-oxidant molecule GSH were significantly reduced in both diseases. Strong positive associations were found between MDA with RANTES/CCL5 and MIP-1β/CCL4 than MCP-1/CCL-2 in SLE patients while a sturdy connotation was seen with MIP-1β/CCL4 and MCP-1/CCL-2 in RA patients. The anti-oxidant molecule GSH shows a negative association with serum levels of MCP-1/CCL-2, RANTES/CCL5 and IP-10/CXCL-10 in SLE patients and with MCP-1/CCL-2 and RANTES/CCL5 in RA patients. A low level of GSH and high level of RANTES/CCL5 were associated with lupus nephritis patients. These results indicates that excessive production of ROS disturbs redox status and can modulate the expression of inflammatory chemokines leading to inflammatory processes, exacerbating inflammation and affecting tissue damage in autoimmune diseases, as exemplified by their strong association with disease activity.
21225699 B cell activation biomarkers as predictive factors for the response to rituximab in rheuma 2011 Apr OBJECTIVE: To examine whether serum B cell markers can predict response to rituximab, a B cell-depleting monoclonal antibody, in patients with refractory rheumatoid arthritis (RA). METHODS: This rituximab re-treatment dose study (SMART [eSsai MAbthera sur la dose de Re-Traitement]) involved 208 patients with refractory RA. Serum markers of B cell activation (anti-cyclic citrullinated peptide [anti-CCP] antibodies, rheumatoid factor [RF], serum IgG, IgA, and IgM levels, serum κ and λ free light chains, and serum BAFF) were assessed before the first rituximab cycle (1,000 mg on days 1 and 15). Univariate and multivariate analyses were performed to identify factors associated with a European League Against Rheumatism (EULAR) response at 24 weeks. RESULTS: There were 149 responders (72%). Two baseline factors were associated with a EULAR response at 24 weeks in multivariate analysis: the presence of anti-CCP antibodies or RF (odds ratio 3.5 [95% confidence interval 1.6-7.6]) and a serum IgG concentration above normal (odds ratio 2.11 [95% confidence interval 1.02-4.33]), with synergy between them (odds ratio 6.0 [95% confidence interval 2.2-16.2]). CONCLUSION: The presence of RF or anti-CCP antibodies and elevated IgG are 2 simple biomarkers that can be used routinely before therapy to predict response to rituximab in patients with refractory RA.
22930755 Human synovial lubricin expresses sialyl Lewis x determinant and has L-selectin ligand act 2012 Oct 19 Lubricin (or proteoglycan 4 (PRG4)) is an abundant mucin-like glycoprotein in synovial fluid (SF) and a major component responsible for joint lubrication. In this study, it was shown that O-linked core 2 oligosaccharides (Galβ1-3(GlcNAcβ1-6)GalNAcα1-Thr/Ser) on lubricin isolated from rheumatoid arthritis SF contained both sulfate and fucose residues, and SF lubricin was capable of binding to recombinant L-selectin in a glycosylation-dependent manner. Using resting human polymorphonuclear granulocytes (PMN) from peripheral blood, confocal microscopy showed that lubricin coated circulating PMN and that it partly co-localized with L-selectin expressed by these cells. In agreement with this, activation-induced shedding of L-selectin also mediated decreased lubricin binding to PMN. It was also found that PMN recruited to inflamed synovial area and fluid in rheumatoid arthritis patients kept a coat of lubricin. These observations suggest that lubricin is able to bind to PMN via an L-selectin-dependent and -independent manner and may play a role in PMN-mediated inflammation.