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ID PMID Title PublicationDate abstract
20360038 Prevalence and risk factors of vertebral fractures in women with rheumatoid arthritis usin 2010 Jul OBJECTIVE: To study the prevalence and risk factors of vertebral fractures (VFs) in a large cohort of patients with RA using VF assessment (VFA). METHODS: We enrolled 172 women with RA, none of whom were taking osteoporosis medications. Patients underwent dual X-ray absorptiometry at the hip and spine and VFA, and completed a questionnaire. Radiological status was assessed by the modified Sharp erosion and narrowing score. VFA was classified using a combination of Genant semi-quantitative approach and morphometry. RESULTS: Patients had a mean (s.d.) disease duration of 8.4 (5.2) years. VFs were detected in 36% (62/172). This group of women had a statistically significant lower weight, height and lumbar spine and total hip BMD and T-scores than those without a VFA-identified VF. They also had more long-standing and severe disease and a greater consumption of corticosteroids. Stepwise regression analysis showed that the presence of VFs was independently associated with low weight and total hip T-score and long disease duration, CRP and Sharp erosion score. CONCLUSION: RA is a risk factor on its own for the development of osteoporosis and VFs and this risk increases more with low weight, disease duration and severe course of disease. These findings may suggest that to prevent the development of VFs, precautions should be taken immediately to suppress the disease activity and correct the weight loss in patients with RA.
19918368 Water-soluble fullerene (C60) inhibits the development of arthritis in the rat model of ar 2009 Recently, it has been demonstrated that oxygen free radicals have an important role as a signaling messenger in the development of inflammation and osteoclastogenesis, suggesting the implication of oxygen free radicals in the pathogenesis of arthritis. The aim of this study was to examine the potential of a strong free-radical scavenger, water-soluble fullerene (C60), as a protective agent against synovitis in arthritis, both in vitro and in vivo. In the presence or absence of C60 (0.1, 1.0, 10.0 muM), human synovial fibroblasts, synovial infiltrating lymphocytes or macrophages were incubated with tumor necrosis factor-alpha (TNF-alpha) (10.0 ng/mL), and the production of proinflammatory cytokines by the individual cells were analyzed. C60 significantly suppressed the TNF-alpha-induced production of proinflammatory cytokines in synovial fibroblasts, synovial infiltrating lymphocytes and macrophages in vitro. Adjuvant induced arthritic rats were used as an animal model of arthritis. Rats were divided into two subgroups: control and treatment with C60 at 10.0 muM. The left ankle joint was injected intraarticularly with water-soluble C60 (20 mul) in the C60-treated group, while, as a control, the left ankle joint in the control rats received phosphate-buffered saline (20 mul), once weekly for eight weeks. Ankle joint tissues were prepared for histological analysis. In adjuvant-induced arthritic rats, intra-articular treatment with C60 in vivo reduced synovitis and alleviated bone resorption and destruction in the joints, while control ankle joints showed progression of synovitis and joint destruction with time. These findings indicate that C60 is a potential therapeutic agent for inhibition of arthritis.
18250111 EULAR evidence-based recommendations for the diagnosis of hand osteoarthritis: report of a 2009 Jan OBJECTIVES: To develop evidence-based recommendations for the diagnosis of hand osteoarthritis (OA). METHODS: The multidisciplinary guideline development group, representing 15 European countries, generated 10 key propositions regarding diagnosis using a Delphi consensus approach. For each recommendation, research evidence was searched for systematically. Whenever possible, the sensitivity, specificity and likelihood ratio (LR) were calculated; relative risk and odds ratios were estimated for risk factors for hand OA. Quality of evidence was categorised using the European League Against Rheumatism (EULAR) hierarchy, and strength of recommendation was assessed by the EULAR visual analogue scale. RESULTS: Diagnostic topics included clinical manifestations, radiographic features, subgroups, differential diagnosis, laboratory tests, risk factors and comorbidities. The sensitivity, specificity and LR varied between tests depending upon the cut-off level, gold standard and controls. Overall, no single test could be used to define hand OA on its own (LR <10) but a composite of the tests greatly increased the chance of the diagnosis. The probability of a subject having hand OA was 20% when Heberden nodes alone were present, but this increased to 88% when in addition the subject was over 40 years old, had a family history of nodes and had joint space narrowing in any finger joint. CONCLUSION: Ten key recommendations for diagnosis of hand OA were developed using research evidence and expert consensus. Diagnosis of hand OA should be based on assessment of a composite of features.
19567625 Increased frequency of gastrointestinal symptoms in patients with fibromyalgia and associa 2009 Aug OBJECTIVE: To determine the frequency and severity of gastrointestinal (GI) symptoms in patients with fibromyalgia (FM). METHODS: We included 152 women with FM (mean age 45.4 +/- 12.2 yrs), 98 women with rheumatoid arthritis (RA; mean age 45.5 +/- 12.3 yrs), and 60 healthy female controls (mean age 44 +/- 11.3 yrs). All patients were questioned about the severity of their chronic widespread pain, symptoms of FM, symptoms of dyspepsia, using a visual analog scale (VAS), and anxiety-depression scale. Patients were asked self-reported (yes/no), symptom-based (>/= 2 criteria) constipation and severity of constipation questions, and about the severity of quality of life (QOL) disturbance secondary to dyspepsia and constipation. RESULTS: Patients with FM had higher symptom severities for belching, reflux, bloating, sour taste, and vomiting than patients with RA and controls (all p values < 0.01). Patients with FM had significantly more dyspepsia-related QOL disturbances than the other 2 groups (p < 0.01). FM and RA patients had more frequent self-reported constipation than controls (respectively, 42.1%, 48%, 21.7%; p < 0.01). The frequency of symptom-based constipation was significantly higher in the RA group (49%) than in FM (29.6%) and control groups (23.3%) (p < 0.01). Constipation-related QOL disturbance was significantly higher in patients with FM than in controls (p < 0.01). CONCLUSION: In patients with FM, the severity scores of dyspepsia symptoms, constipation, and dyspepsia-related QOL disturbance were higher than in patients with RA and controls. The higher GI symptom severity in patients with FM might have negative effects on their QOL.
20039406 Rheumatoid arthritis-specific autoantibodies to peptidyl arginine deiminase type 4 inhibit 2010 Jan OBJECTIVE: Autoantibodies to citrullinated proteins are specific for rheumatoid arthritis (RA) and recognize epitopes centered by citrulline, a posttranslationally modified form of arginine. Peptidyl arginine deiminase type 4 (PAD-4), the enzyme that converts arginine into citrulline, is in itself a target for RA-specific autoantibodies. This study was undertaken to assess whether anti-PAD-4 autoantibodies interfere with citrullination in vitro in patients with RA, and to identify peptide targets of anti-PAD-4 antibodies that can activate or inhibit citrullination. METHODS: To test whether autoantibodies to PAD-4 influence citrullination, an in-house citrullination assay was developed using purified autoantibodies to PAD-4. To map B cell epitopes on PAD-4, 65 overlapping 20-mer peptides encompassing the entire PAD-4 were analyzed for their reactivity in RA sera. RESULTS: Autoantibodies to PAD-4 inhibited PAD-4-mediated citrullination. Three linear peptides on PAD-4 were recognized almost uniquely by PAD-4 autoantibodies in the sera of patients with RA. One peptide was located in the N-terminal, calcium-binding domain of PAD-4, while 2 other peptides were located in the C-terminal, substrate-binding domain of PAD-4. CONCLUSION: Autoantibodies to PAD-4 inhibit in vitro citrullination of fibrinogen by PAD-4. Most anti-PAD-4-positive sera recognize peptides located both in the N-terminal domain (211-290) and the C-terminal domain (601-650) of PAD-4.
20646335 Updating the physiology, exploration and disease relevance of complement factor H. 2010 Apr The factor H (FH) protein (also known as beta1H globulin) is the main regulator of the complement alternative pathway. It exhibits multivalent binding sites to the complement component C3b, and polyanions and one binding site to sialic acid and cell surfaces. These multiple binding sites confer to FH a decay-accelerating factor activity in the fluid phase as well as at the cell surface. A defect in FH activity or a FH protein deficiency triggers chronic inflammation and tissue injury, leading to various disorders impacting the kidney or the eye. In contrast, some pathogens, as well as cancer cells, develop various strategies to bind FH and thereby subvert a complement attack. We focus on the functions of FH, and review the main pathological conditions in which FH is involved. Since the pathogenesis is elusive, appropriate FH dosage in biological fluids and FH gene analysis may help in improving understanding of such diseases.
20877977 Oral events related to low-dose methotrexate in rheumatoid arthritis patients. 2010 Jul Low-dose methotrexate (MTX) is frequently used for patients with rheumatoid arthritis (RA). High doses of MTX frequently produce side effects. The aim of this study was to explore oral complications of low-dose MTX therapy in a population of RA patients. This is a cross-sectional study in which oral examination was performed on a population of RA patients. Patients undergoing MTX therapy (5-20 mg weekly) for at least six months were included in the study group, and RA patients being treated under another regimen were used as controls. The frequency of oral lesions was compared between groups. The chi-square test was used to compare frequencies. Relative risk (RR) and its confidence interval (CI) were established. Significance level was set at 0.05. Twenty-eight RA patients on a low-dose MTX regimen and 21 controls were enrolled in the study. Oral lesions were found in 22 patients (78.6%) undergoing MTX therapy, and in 5 patients (23.8%) undergoing other therapies (p < 0.001). There were no significant differences regarding age, gender or dosage. The most common oral events observed in patients in the MTX group were ulcerative/erosive lesions (60.7%) and candidiasis (10.7%). Patients in the control group presented lower prevalence of the same lesions (p < 0.001). The RR for developing oral lesions was 11.73 (CI 2.57 - 58.98), with low-dose MTX therapy. In conclusion, the prevalence of oral mucosa lesions in RA patients receiving low doses of MTX therapy is higher than in RA patients not receiving the drug.
21097159 Polymerase chain reaction (PCR) and sequence specific oligonucleotide probes (SSOP) genoty 2010 In this paper an assay for the detection of genes associated with rheumatoid arthritis (RA) and multiple sclerosis, using polymerase chain reaction (PCR) and sequence specific oligonucleotide probes (SSOP) is presented, in order to be further applied in a portable Lab-On-Chip (LOC) device. A substantial part of these reagents were based on the literature (11th International Histocompatibility Workshop, IHW), bearing the advantage of proven successful implementation in genotyping, while others were designed for this study. More precisely, our methodology discriminates HLA-DRB1 as DRB1*01, *04 and *10, which include shared epitope (SE) alleles associated with RA and additionally DRB1*15 allele, including DRB1*1501 associated with MS (broad genotyping method). To further present the basic elements of the assay for high resolution genotyping of SE DRB1 alleles, we provide as an example the case of HLA-DRB1*10 alleles (HLADRB1* 100101, *100102, *100103, *1002 and *1003). Regarding the methodology for developing a detection assay, for SNPs associated with RA or MS the basic steps are presented. DNA sequence data are obtained from IMGT/HLA and SNP database. Online software tools are used to define hybridization specificity of primers and probes towards human DNA, leading to hybridization patterns that uniquely designate a target allele and evaluate parameters influencing PCR efficiency. Respecting current technological limitations of autonomous molecular-based LOC systems the approach of broad genotyping of HLA-DRB1*01/*04/*10/*15 genes, is intended to be initially used, leaving, high resolution genotyping of SE alleles for future implementations. This method is easy to be updated and extended to detect additional associated loci with RA or MS.
20037504 Challenges in economic evaluation of new drugs: experience with rituximab in Hungary. 2010 Jan BACKGROUND: Implementation of a new therapy into clinical practice is a complex process. Various countries have different requirements for information but most often focus on economic evaluation, which often plays a stronger role in healthcare decision making than does clinical evidence. MATERIAL/METHODS: To identify all potential challenges in economic evaluation, the case of a new biological drug, rituximab, used to treat rheumatoid arthritis, has been taken as an example. We present methods and results of economic assessment, highlighting the specific issues that should be considered in countries with economic and health care conditions similar to those of Hungary. RESULTS: In principle, economic evaluation requires data on characteristics of target population, disease progression, treatment impact, preferences, resource utilization and unit prices. Treatment effect/relative risk reduction and clinical practice patterns (resource use) may be more generalizable, whereas prices and baseline risk need to be jurisdiction specific. In order to address issues of transferability, investments need to be made in the collection of epidemiological and demographic data, plus data on clinical practice patterns, resource use, costs and health state valuation. In Hungary this problem has been solved through conducting a well designed 255 patient cross-sectional study. CONCLUSIONS: The Hungarian example shows that there should be more investment in data collection for those parameters that are thought to differ most from place to place. Owing to the similarities between Central and Eastern Europe countries in health care systems, clinical practice patterns and economic indicators, they may be able to develop partnerships to develop relevant regional databases and registries.
18848647 Antibody responses to Porphyromonas gingivalis (P. gingivalis) in subjects with rheumatoid 2009 Jan Antibody titers to P. gingivalis are increased in patients with rheumatoid arthritis and are associated with disease-specific autoimmunity. BACKGROUND: Periodontitis (PD) has been implicated as a risk factor for rheumatoid arthritis (RA). We sought to characterize antibody titers to P. gingivalis (a pathogen in PD) in subjects with RA, PD, and in healthy controls and to examine their relationship with disease autoantibodies. METHODS: P. gingivalis antibody was measured in subjects with RA (n=78), PD (n=39), and in controls (n=40). Group frequencies of bacterial titer elevations were compared using the Chi-square test and antibody titers were compared using non-parametric tests. Correlations of P. gingivalis titer with C-reactive protein (CRP), antibody to cyclic citrullinated peptide (anti-CCP), and rheumatoid factor (RF) were examined in those with RA while CRP and autoantibody concentrations were compared based on seropositivity to P. gingivalis. RESULTS: Antibody titers to P. gingivalis were highest in PD, lowest in controls, and intermediate in RA (p=0.0003). Elevations in P. gingivalis (titer> or =800) were more common in RA and PD (67% and 77%, respectively) than in controls (40%) (p=0.002). In RA, there were significant correlations with P. gingivalis titer with CRP, anti-CCP-IgM, and -IgG-2. CRP (p=0.006), anti-CCP-IgM (p=0.01) and -IgG2 (p=0.04) concentrations were higher in RA cases with P. gingivalis titers > or =800 compared to cases with titers <800. CONCLUSION: Antibodies to P. gingivalis are more common in RA subjects than controls, although lower than that in PD. Associations of P. gingivalis titers with RA-related autoantibody and CRP concentrations suggests that infection with this organism plays a role in disease risk and progression in RA.
19733258 Lysophosphatidic acid mediates migration of human mesenchymal stem cells stimulated by syn 2010 Jan Migration of mesenchymal stem cells plays a key role in regeneration of injured tissues. Rheumatoid arthritis (RA) is a chronic inflammatory disease and synovial fluid (SF) reportedly contains a variety of chemotactic factors. This study was undertaken to investigate the role of SF in migration of human bone marrow-derived mesenchymal stem cells (hBMSCs) and the molecular mechanism of SF-induced cell migration. SF from RA patients greatly stimulated migration of hBMSCs and the SF-induced migration was completely abrogated by pretreatment of the cells with the lysophosphatidic acid (LPA) receptor antagonist Ki16425 and by small interfering RNA- or lentiviral small hairpin RNA-mediated silencing of endogenous LPA(1)/Edg2. Moreover, SF from RA patients contains higher concentrations of LPA and an LPA-producing enzyme autotoxin than normal SF. In addition, SF from RA patients increased the intracellular concentration of calcium through a Ki16425-sensitive mechanism and pretreatment of the cells with the calmodulin inhibitor W7 or calmodulin-dependent protein kinase II inhibitor KN93 abrogated the SF-induced cell migration. These results suggest that LPA-LPA(1) plays a key role in the migration of hBMSCs induced by SF from RA patients through LPA(1)-dependent activation of calmodulin-dependent protein kinase II.
19199253 [Association of the PADI4 gene polymorphism and HLA-DRB1 shared epitope alleles with rheum 2009 Feb OBJECTIVE: To investigate the association of single nucleotide polymorphisms (SNPs) of the peptidylarginine deiminase IV (PADI4) and HLA-DRB1 shared epitope (SE) alleles with rheumatoid arthritis(RA) in a Chinese population. METHODS: Four exonic SNPs of the PADI4 gene (PADI 4_89*A/G, PADI 4_90*C/T, PADI 4_92*C/G and PADI 4_104*C/T) were genotyped in 67 unrelated patients with RA and 81 healthy controls, using cDNA sequencing and T vector cloning. HLA-DRB 1*01, *04 and *10 subtypes were determined by polymerase chain reaction with sequence specific primers (PCR-SSP). RESULTS: The distributions of the 4 SNPs were different in the two groups, and increased RA susceptibility was significantly associated with the minor alleles of PADI 4_89*G (P was 0.023), PADI 4_90*T (P was 0.004), PADI 4_104*T (P was 0.003), and the haplotypes carrying the 4 minor alleles (P was 0.008). HLA-DRB1 SE alleles are composed of HLA-DRB 1*0101, *0102, *0401, *0404, *0405, *0408, *0409, *0410 and *1001. Individuals carrying the SE alleles were associated with increased RA susceptibility (P was 0.002). Individuals carrying both the SE alleles and minor alleles of the 4 SNPs were more susceptible to RA than individuals carrying neither the minor SNP alleles nor the SE alleles. CONCLUSION: The PADI4 SNPs and haplotypes are associated with RA susceptibility in Chinese. HLA-DRB1 shared epitope is also an important risky factor for RA. There may exist certain synergistic effect between the PADI4 minor alleles and the HLA-DRB1 shared epitope.
20884980 Mid-term results of a metal-backed glenoid component in total shoulder replacement. 2010 Oct Total shoulder replacement is a successful procedure for degenerative or some inflammatory diseases of the shoulder. However, fixation of the glenoid seems to be the main weakness with a high rate of loosening. The results using all-polyethylene components have been better than those using metal-backed components. We describe our experience with 35 consecutive total shoulder replacements using a new metal-backed glenoid component with a mean follow-up of 75.4 months (48 to 154). Our implant differs from others because of its mechanism of fixation. It has a convex metal-backed bone interface and the main stabilising factor is a large hollow central peg. The patients were evaluated with standard radiographs and with the Constant Score, the Simple Shoulder Test and a visual analogue scale. All the scores improved and there was no loosening, no polyethylene-glenoid disassembly and no other implant-related complications. We conclude that a metal-backed glenoid component is a good option in total shoulder replacement with no worse results than of those using a cemented all-polyethylene prosthesis.
20499390 Do fall predictors in middle aged and older adults predict fall status in persons 50+ with 2010 Jun We explored potential predictors of fall status in 70 community-dwelling persons > or =50 years of age with fibromyalgia (FM). Over 40% of the sample reported one or more falls in the year prior to the study. A logistic regression model using 10 variables known to predict falls in middle aged and older persons predicted 45% of the variance in fall status. Three variables offered significant independent contributions to the overall model predicting fall status: perception of postural instability, balance performance, and executive function processing speed. The results support prior work in both nonclinical and clinical populations of middle aged and older adults indicating that falls are associated with multiple risk factors. Prospective designs with larger samples are needed to (a) validate and extend these findings, and (b) identify risk factors related to fall status that are unique to persons with FM.
20939474 [Comparison of clinical results between high-flexion and standard cruciate-stabling prosth 2010 Sep OBJECTIVE: To compare the clinical results between high-flexion and standard cruciate-stabling prostheses in total knee arthroplasty (TKA) by using the 36-item short form health survey (SF-36). METHODS: Between August 2007 and January 2009, 98 patients (106 knees) underwent TKA with standard cruciate-stabling prostheses (standard group), and 46 patients (50 knees) underwent TKA with high-flexion prostheses (high-flexion group). In standard group, there were 30 males (32 knees) and 68 females (74 knees) with an age of (70.0 +/- 3.5) years, including 78 cases (82 knees) of osteoarthritis (OA) and 20 cases (24 knees) of rheumatoid arthritis (RA) with a disease duration of (14.5 +/- 3.3) years; the Hospital for Special Surgery Scoring System (HSS) and the range of motion (ROM) were 56.1 +/- 21.6 and (89.0 +/- 16.1) degrees, respectively. In high-flexion group, there were 8 males (10 knees) and 38 females (40 knees) with an age of (68.6 +/- 8.9) years, including 44 cases (47 knees) of OA and 2 cases (3 knees) of RA with a disease duration of (13.9 +/- 4.1) years; the HSS and ROM were 58.9 +/- 25.3 and (91.0 + 19.3) degrees, respectively. There was no significant difference in the general data (P > 0.05) between 2 groups, so the clinical data of 2 groups had comparability. RESULTS: In standard group, poor wound healing and persistent headache caused by cerebrospinal fluid leakage occurred in 1 case, respectively. In high-flexion group, transient common peroneal nerve palsy occurred in 1 case. There was significant difference (P < 0.05) in the hospitalization expense between standard group [yen(39,000 +/- 6000)] and high-flexion group [yen (52,000 +/- 8 000)]. The follow-up time was 12-26 months (18 months on average) in standard group (91 cases, 98 knees) and 11-19 months (13 months on average) in high-flexion group (44 cases, 47 knees). The SF-36 showed significant difference in role-physical score (P < 0.05), but no significant difference in other 7 indices scores (P > 0.05). At the final follow- up, the ROM was (129.1 +/- 19.2) degrees in high-flexion group and (123.6 +/- 16.7) degrees in standard group; showing significant difference (P < 0.05). The HSS was 91.2 +/- 17.6 in high-flexion group and 92.5 +/- 14.5 in standard group; showing no significant difference (P > 0.05). CONCLUSION: After TKA, the ROM in high-flexion group is superior to that in standard group, but there is no obvious advantages in terms of the HSS and SF-36 outcomes.
20635999 Golimumab as the first monthly subcutaneous fully human anti-TNF-alpha antibody in the tre 2010 Jul Golimumab (Simponi, Centocor Ortho Biotech Inc., PA, USA) is the first transgenic human monoclonal antibody against TNF-alpha that has been approved in the treatment of rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. Golimumab is synthesized using conventional hybridoma technique after immunizing transgenic mice containing human immunoglobulin genes. The constant region of golimumab is identical to that of infliximab, but the variable regions of golimumab have fully human sequences. In this article, we present the pharmacodynamic and pharmacokinetic properties as well as the clinical efficacy and tolerability of golimumab.
21067435 Use of a trabecular metal implant in ankle arthrodesis after failed total ankle replacemen 2010 Dec BACKGROUND AND PURPOSE: Arthrodesis after failed total ankle replacement is complicated and delayed union, nonunion, and shortening of the leg often occur-especially with large bone defects. We investigated the use of a trabecular metal implant and a retrograde intramedullary nail to obtain fusion. PATIENTS AND METHODS: 13 patients with a migrated or loose total ankle implant underwent arthrodesis with the use of a retrograde intramedullary nail through a trabecular metal Tibial Cone. The mean follow-up time was 1.4 (0.6-3.4) years. RESULTS: At the last examination, 7 patients were pain-free, while 5 had some residual pain but were satisfied with the procedure. 1 patient was dissatisfied and experienced pain and swelling when walking. The implant-bone interfaces showed no radiographic zones or gaps in any patient, indicating union. INTERPRETATION: The method is a new way of simplifying and overcoming some of the problems of performing arthrodesis after failed total ankle replacement.
19284558 Candidate autoantigens identified by mass spectrometry in early rheumatoid arthritis are c 2009 INTRODUCTION: The aim of our study was to identify new early rheumatoid arthritis (RA) autoantibodies. METHODS: Sera obtained from 110 early untreated RA patients (<6 months) were analyzed by western blot using HL-60 cell extract, separated on one-dimensional and two-dimensional gel electrophoresis (1-DE, 2-DE). Sera from 50 healthy blood donors and 20 patients with non-RA rheumatisms were used as controls for 1-DE and 2-DE, respectively. The immunoreactive proteins were identified by MALDI-TOF mass spectrometric analysis and the presence of potential sites of citrullination in each of these proteins was evaluated. FT-ICR mass spectrometry was used to verify experimentally the effect of citrullination upon the mass profile observed by MALDI-TOF analysis. RESULTS: The 110 1-DE patterns allowed detection of 10 recurrent immunoreactive bands of 33, 39, 43, 46, 51, 54, 58, 62, 67 and 70 kDa, which were further characterized by 2-DE and proteomic analysis. Six proteins were already described RA antigens: heterogeneous nuclear ribonucleoprotein A2/B1, aldolase, alpha-enolase, calreticulin, 60 kDa heat shock protein (HSP60) and BiP. Phosphoglycerate kinase 1 (PGK1), stress-induced phosphoprotein 1 and the far upstream element-binding proteins (FUSE-BP) 1 and 2 were identified as new antigens. Post-translational protein modifications were analyzed and potentially deiminated peptides were found on aldolase, alpha-enolase, PGK1, calreticulin, HSP60 and the FUSE-BPs. We compared the reactivity of RA sera with citrullinated and noncitrullinated alpha-enolase and FUSE-BP linear peptides, and showed that antigenicity of the FUSE-BP peptide was highly dependent on citrullination. Interestingly, the anti-cyclic citrullinated peptide antibody (anti-CCP2) status in RA serum at inclusion was not correlated to the reactivity directed against FUSE-BP citrullinated peptide. CONCLUSIONS: Two categories of antigens, enzymes of the glycolytic family and molecular chaperones are also targeted by the early untreated RA autoantibody response. For some of them, and notably the FUSE-BPs, citrullination is involved in the immunological tolerance breakdown observed earlier in RA patients. Autoantibodies recognizing a citrullinated peptide from FUSE-BP may enhance the sensibility for RA of the currently available anti-CCP2 test.
18792423 Providing patients with information about disease-modifying anti-rheumatic drugs: Individu 2009 Jun BACKGROUND: Communicating information about disease-modifying anti-rheumatic drugs (DMARDs) before patients start treatment is a key role for some rheumatology clinical nurse specialists. This is done in our unit to promote understanding of the risks and benefits of drug therapy and encourage timely and reliable use of DMARDs. Information is routinely provided individually but this can lead to delays in starting treatment because of limited nursing resources. In this randomized trial we tested the feasibility of giving patients, who were about to start on a DMARD, information about the drug in groups and compared this with information given individually. METHODS: Adults with a clinical diagnosis of rheumatoid arthritis or psoriatic arthritis who were referred to the nursing team for counselling about starting on methotrexate, sulfasalazine or leflunomide were included. Patients who had previously taken a DMARD were not excluded and those consenting were randomized to receive drug information individually or in groups (of three to six patients). We provided all patients with written materials about the relevant drug and discussed the risks and benefits of drug use verbally. Patients allocated to group counselling received this intervention in a teaching room, with a slide presentation. The primary outcome was adherence with medication use, ascertained by pill counts, self-report diaries and prescription dispensation. Secondary outcomes included satisfaction with information about medicines (SIMS) by questionnaire; time taken to provide information; adherence to scheduled hospital appointments and blood monitoring schedules; and DMARD continuation rates at four and twelve months. RESULTS: Of 127 eligible patients referred for counselling about DMARDs, 62 consented to take part: 32 were randomized to receive drug information individually and 30 to receiving it in groups. Patients allocated to the two different interventions were comparable for age and diagnoses at baseline but more patients allocated individual counselling had not taken a DMARD previously: 56% (18/32) versus 20% (6/30). More patients counselled in groups were adherent (27/30; 90%) compared with patients counselled individually (22/32; 69%; p = 0.06) by pill counts. However, on self-report diaries, similar proportions were adherent (group counselling 97% (29/30) versus individual 94% (30/32); p = 1.0). All but two prescriptions were dispensed. More patients allocated to individual counselling missed at least one blood monitoring visit (25% versus 17%; p = 0.54) and at least one scheduled clinic visit (19% versus 3%; p = 0.10). SIMS scores indicated high levels of patient satisfaction and were similar for both groups. The time taken to run group and individual counselling sessions were similar (median of 35 minutes versus 33 minutes, respectively). Nursing time per individual patient in those allocated group counselling was 11.6 minutes. Drug continuation rates were higher for those counselled in groups compared with those counselled individually: at four months, 73% versus 63 %; p = 0.42; at twelve months, 47% versus 38%; p = 0.61). CONCLUSIONS: Our pilot study demonstrated the feasibility of providing counselling on DMARDs to groups of patients with important time savings for specialist nurses and while maintaining high levels of patient satisfaction. There was a trend for better outcomes in terms of adherence and drug continuation rates for patients counselled in groups, indicating potential benefits from group interactions. However, these findings need to be investigated further in a larger, fully powered trial.
20072851 Interleukin-32gamma enhances the production of IL-6 and IL-8 in fibroblast-like synoviocyt 2010 Mar INTRODUCTION: In the present study, we examined the effect of the pro-inflammatory cytokine IL-32gamma, the most biologically active isoform, and its related molecules in fibroblast-like synoviocytes (FLS). MATERIALS AND METHODS: FLS were isolated from synovial tissues of rheumatoid arthritis (RA) patients. The secretion and expression of IL-6 and IL-8 were examined by ELISA and real-time PCR, and the activation of signaling molecules was evaluated by Western blot, electrophoretic mobility shift assay (EMSA), real-time PCR, and siRNA transfection. RESULTS: By IL-32gamma stimulation in RA FLS, the expressions of IL-6 and IL-8 were increased significantly, and the phosphorylated Erk1/2 and AP-1 were expressed prominently in Western blot and EMSA. In the Erk1/2 inhibited cells, IL-32gamma stimulation did not increase the mRNA expression of IL-6 and IL-8. CONCLUSION: Our results suggest that IL-32gamma stimulation can induce the production of IL-6 and IL-8 from RA FLS via Erk1/2 activation.