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ID PMID Title PublicationDate abstract
17134602 [Rituximab (MabThera) as treatment of active rheumatoid arthritis]. 2006 Nov 20 Rituximab (RTX) is a murine/human monoclonal antibody to CD20, a protein expressed almost exclusively on human B-lymphocytes. RTX induces rapid and marked B-cell depletion with beneficial clinical effects in 1/3 to 1/2 of rheumatoid arthritis patients. Treatment is given as two iv. infusions with a two-week interval and in combination with methotrexate. Mild to moderate side-effects are frequent, particularly during the first infusion, but long-term side-effects are generally rare, although pulmonary events and reactivation of viral infections of the liver is of concern.
18640855 Incidence and risk factors for blood transfusion in total elbow arthroplasty. 2008 Nov Our purpose was to determine the incidence of transfusion in consecutive patients undergoing total elbow arthroplasty and examine the risk factors for transfusion. Between January 1, 1998, and December 31, 2002, 378 primary total elbow arthroplasties were performed. Risk factors analyzed included the preoperative level of hemoglobin, age, gender, and diagnosis. Indications for transfusion and associated complications were reviewed. The overall transfusion rate was 2.9%. Men and women had a similar incidence of transfusion. The risk of transfusion was not different between patients who underwent elbow arthroplasty for sequelae of trauma, rheumatoid arthritis, or osteoarthritis. Low preoperative hemoglobin level (P = .0002) and older age (P = .015) were risk factors for transfusion. There was no statistical difference in risk of transfusion by operative time. These data demonstrate that the rate of transfusion for total elbow arthroplasty varies by patient age and preoperative level of hemoglobin.
17013997 Psoriasis induced by tumor necrosis factor-alpha antagonist therapy: a case series. 2007 Feb OBJECTIVE: Although tumor necrosis factor-alpha (TNF-alpha) antagonists are effective in the treatment of refractory psoriasis, some cases have suggested that psoriasis might be induced as a result of treatment prescribed mainly for rheumatoid arthritis, ankylosing spondylitis, and Crohn's disease. To investigate anti-TNF-alpha induced psoriasis, we conducted a systematic analysis of the 6 cases we observed among our inflammatory patient cohort treated with anti-TNF-alpha (infliximab or etanercept). METHODS: We report 6 cases of psoriasis with onset during TNF-alpha antagonist therapy (infliximab and etanercept); characteristics and skin lesions are described. RESULTS: No patient had a personal or family history of psoriasis. The development of psoriasis was seen in all the types of inflammatory diseases we treated with TNF-alpha antagonists. There was great variation in the age of affected patients and in the onset of psoriasis after initiation of TNF-alpha antagonists. Both TNF-alpha antagonists studied were associated with development of psoriasis. In 2 cases psoriasis was associated with 2 different TNF-alpha antagonists in the same patient. In half our patients, skin lesions started in the inguinal and pubic regions, but palmoplantar pustulosis was also common. In half the cases, skin lesions responded favorably with topical agents despite continuation of TNF-alpha antagonist therapy. CONCLUSION: In light of previously published cases describing psoriasis or psoriasiform lesions after TNF-alpha antagonist therapy, our series strongly confirms that TNF-alpha antagonists may induce psoriasis in some patients. Further studies are needed to identify risk factors for TNF-alpha antagonist induced psoriasis.
18240257 The prevalence of foot ulceration in patients with rheumatoid arthritis. 2008 Feb 15 OBJECTIVE: To establish the prevalence of foot ulceration in patients with rheumatoid arthritis (RA) in secondary care. METHODS: A postal survey of all patients with RA (n = 1,130) under the care of rheumatologists in Bradford, West Yorkshire, UK was performed. The prevalence data were validated through clinical examination, case-note review, and contact with health professionals. The false-negative rate was investigated in a subsample of patients (n = 70) who denied any history of ulceration. RESULTS: The postal survey achieved a 78% response rate. Following validation, the point prevalence of foot ulceration was 3.39% and the overall prevalence was 9.73%. The false-positive rate was initially high at 21.21%, but use of diagrammatic questionnaire data to exclude leg ulceration reduced the rate to 10.76%. The false-negative rate was 11.76%. The most common sites for ulceration were the dorsal aspect of hammer toes, the metatarsal heads, and the metatarsophalangeal joint in patients with hallux abducto valgus, with 33% of patients reporting multiple sites of ulceration. Patients with open-foot and healed-foot ulceration had significantly longer RA disease duration, reported significantly greater use of special footwear, and had a higher prevalence of foot surgery than ulcer-free patients. CONCLUSION: Foot ulceration affects a significant proportion of patients with RA. Further work is needed to establish risk factors for foot ulceration in RA and to target foot health provision more effectively.
18782565 Sinomenine ameliorates arthritis via MMPs, TIMPs, and cytokines in rats. 2008 Nov 14 Rheumatoid arthritis (RA) is a chronic, inflammatory autoimmune disease that results in progressive joint destruction and substantial morbidity. The stem of the Chinese medicinal plant, Sinomenium acutum Rehder & Wilson (Family Menispermaceae), has been used to treat various rheumatic and arthritic diseases, of which the major bioactive component is sinomenine. We investigated the nature and molecular mechanisms of the anti-arthritic effect of sinomenine on collagen-induced arthritis in female Wistar rats. The results showed that sinomenine markedly suppressed the incidence and disease progression of established CIA, showing as dramatic reduction of paw swelling, ESR, and arthritic scores. Sinomenine suppressed the production of proinflammatory cytokines IL-1beta and IL-6 in serum, inhibited the protein expressions and activities of MMP-2 and MMP-9, and elevated the protein expressions and activities of TIMP-1 and TIMP-3 in rat paw tissues.
17477816 In vitro evaluation of leukemia inhibitory factor receptor antagonists as candidate therap 2007 Apr Leukemia inhibitory factor (LIF) and oncostatin M (OSM) are found in appreciable concentrations in synovial fluid from patients with rheumatoid arthritis (RA) but not osteoarthritis. Accordingly, both are potential therapeutic targets in inflammatory diseases of the joints. Several LIF antagonists have been developed. They have the capacity to inhibit the biologic activities of not only LIF but also other interleukin-6 (IL-6) subfamily cytokines, including OSM. Both LIF and OSM share the same receptor, which is part of a cytokine receptor super family in which the glycoprotein 130 (gp130) subunit is a common constituent. The aim of this study was to evaluate the antagonistic potentials of two LIF mutants, LIF05 and MH35-BD. Both are mutant forms of human LIF with reduced affinity for gp130 and greater LIF receptor (LIFR) binding affinity. The results, using Ba/F3 cell proliferation assay, acute-phase protein (haptoglobin) induction analysis in HepG2 human hepatoma cells, a porcine cartilage glycosaminoglycan release assessment for proteoglycan degradation, and a collagen release assay, show that these antagonists inhibit relevant LIF, OSM, and other IL-6 subfamily cytokines in vitro albeit with differential potencies and have, therefore, therapeutic potential for treatment of RA and perhaps other diseases.
17896808 Longterm culture of telomerase-transduced rheumatoid arthritis fibroblast-like synoviocyte 2007 Oct OBJECTIVE: To extend the lifespan of rheumatoid arthritis fibroblast-like synoviocytes (RA FLS) using human telomerase catalytic subunit (hTERT) and to test the hypothesis that longterm culture of hTERT-RA FLS may display a disease-specific gene expression pattern. METHODS: RA 516 FLS were transduced by hTERT and the replicative properties of hTERT-RA 516 FLS were evaluated by repeated expansion. Gene expressions in hTERT-RA 516 FLS (passage 8) were compared with the gene expressions in hTERT-osteoarthritis (OA) 13A FLS (passage 8) by microarrays and RT-PCR. After continuous expansion in culture for an additional 4 months, gene expression was examined again using real-time RT-PCR and microarray. RESULTS: While primary RA 516 FLS stopped dividing after repeated culture for about 120 days, hTERT-RA 516 FLS continued to grow at a steady rate. The hTERT-RA 156 FLS displayed a distinct gene expression pattern different from hTERT-OA 13A FLS. Several putative autoantigens and cytokine A2/monocyte chemoattractant protein-1 were expressed at significantly higher levels in longterm culture of hTERT-RA 516 FLS. CONCLUSION: Telomerase-transduced RA FLS offer an alternative cell model for the study of RA and for examination of cellular/genetic alterations in RA FLS. Our findings provide further support for the notion that RA FLS are altered cells.
17462505 Is FCRL3 a new general autoimmunity gene? 2007 May Autoimmunity is a multistep pathogenic process, which arises in genetically predisposing individuals as a result of the harmful influence of environmental factors causing the breakdown of immune tolerance and induction of self-reactive immune response. Recent findings resolved common pathogenic mechanisms shared between different autoimmune diseases and suggested for the existence of genetic loci that could be involved in general autoimmunity and hence contribute to susceptibility of several autoimmune diseases. To date, several loci responsible for general autoimmunity have been identified. The Fc receptor-like 3 (FCRL3) gene is one of those loci for which a significant association with a number of autoimmune diseases such as rheumatoid arthritis (RA), autoimmune thyroid disease, and systemic lupus erythematosus (SLE) has been recently shown in Japanese. However, studies in Caucasians failed to confirm a strong association of this gene with RA and SLE and therefore made questionable the putative role of FCRL3 in general autoimmunity. In this review, we discuss whether the FCRL3 gene is a newly discovered gene contributing to shared susceptibility between autoimmune diseases.
17549762 Detecting haplotype effects in genomewide association studies. 2007 Dec The analysis of genomewide association studies requires methods that are both computationally feasible and statistically powerful. Given the large-scale collection of single nucleotide polymorphisms (SNPs), it is desirable to explore the information contained in their interrelationships. In particular, utilizing haplotypes rather than individual SNPs and accounting for correlations of polymorphisms in adjustment for multiple testing can lead to increased power. We present a statistically powerful and numerically efficient method based on sliding windows of adjacent SNPs to detect haplotype-disease association in genomewide studies. This method consists of an efficient algorithm to calculate a proper likelihood-ratio statistic for any given window of SNPs, along with an accurate and efficient Monte Carlo procedure to adjust for multiple testing. Simulation studies using the HapMap data showed that the proposed method performs well in realistic situations. We applied the new method to a case-control study on rheumatoid arthritis and identified several loci worthy of further investigations.
17553352 [The role of IFN-gamma, IL-10, IL-12 and TRAIL in sera and synovium fluids from patients w 2007 Jun AIM: To study on the role of IFN-gamma, IL-10, IL-12 and TRAIL in the pathogenesis of RA. METHODS: The concentrations of IFN-gamma, IL-12, IL-10 and TRAIL in synovium fluid and sera isolated from 46 patients with RA were determined by Sandwich ELISA. RESULTS: The concentrations (ng/L) of IFN-gamma, IL-12 and TRAIL in synovium fluids from the patients were (106.2+/-7.8), (57.7+/-3.5) and (166.5+/-12.3), respectively. The concentrations (ng/L) of these cytokines in sera from the patients were (56.3+/-7.4), (35.1+/-12.7), (69.5+/-8.3) and in sera from the healthy donors (31.1+/-4.4), (25.2+/-2.6) and (41.2+/-4.8). The levels of cytokines mentioned above in synovium fluid from the patients were higher than those in sera from both the patients and the healthy individuals (P<0.05, P<0.01). There was no significant difference of concentration of IL-10 between the patients and the healthy donors. CONCLUSION: The levels of IFN-gamma, IL-12 and TRAIL in synovium fluid from the patients with RA are higher than those in healthy donors. This result indicates that the pattern of cytokine on course of RA is main of Th1, more typical in synovium fluid than in serum. Analysis of the concentration of IFN-gamma, IL-12, IL-10 and TRAIL in the serum may be useful to diagnosis and bio-immunological treatment of the RA patients correctly.
18036033 The quantitative analysis of peripheral blood FOXP3-expressing T cells in systemic lupus e 2007 Dec BACKGROUND: Expressed in naturally occurring CD4+CD25+ regulatory T cells, FoxP3 plays an important role in maintaining immune tolerance. We therefore evaluated the possibility that the peripheral blood FOXP3+ T-cell deficiency is associated with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). MATERIALS AND METHODS: The FOXP3 expression in peripheral blood T cells were evaluated and correlated to the CD4 and CD25 expression by flow cytometric analysis. Cell frequencies of FOXP3+ T cells among CD4+ T cells and absolute FOXP3+ T cell counts in SLE and RA patients were determined for the statistical comparison with those in normal controls, and their correlation with disease activities in SLE patients was evaluated. The FOXP3 transcript levels in peripheral blood mononuclear cells (PBMCs) were also determined to correlate the FOXP3+ T-cell quantity and to evaluate the possible dysregulation in the expression of two FOXP3 mRNA variants in patients. RESULTS: SLE patients had the higher FOXP3+ T-cell frequency and absolute CD4+CD25-FOXP3+ cell count than normal individuals, and the frequencies of CD4+CD25+FOXP3+ and CD4+FOXP3+ cells were positively correlated with the disease activities in SLE patients. In contrast, the differences in frequencies and absolute counts of FOXP3+ T cells between normal controls and RA patients were found to be insignificant. Moreover, SLE and RA patients appear to express two FOXP3 transcript variants in peripheral blood mononuclear cells at the levels similar to normal individuals. CONCLUSIONS: The peripheral blood FOXP3+ T-cell frequency among CD4+ T cells is altered in SLE patients with the active disease activity. Therefore, the analysis on peripheral blood FOXP3+ T cells may be useful for the evaluation of lupus disease activity.
18299302 Psoriasiform lesions induced by tumour necrosis factor antagonists: a skin-deep medical co 2008 Aug Rarely, tumour necrosis factor (TNF)alpha antagonist therapy has been associated with de novo psoriasiform eruptions. This is unusual in that these same drugs are used to treat psoriasis. Most of these cases involve the palms and soles, yet palmoplantar pustular psoriasis represents only 1.7% of all cases of psoriasis. Keratoderma blenorrhagicum is a psoriasiform rash that occurs primarily on the palms and soles of some patients with reactive arthritis. It is grossly and histologically indistinguishable from pustular psoriasis. Chlamydia trachomatis is a common aetiological agent for reactive arthritis, and in vitro studies have shown that chlamydial replication is inversely proportional to TNFalpha levels. Three patients taking TNFalpha antagonists are presented who developed such lesions and who were found to be positive for C trachomatis DNA in the affected skin. It is proposed that these psoriasiform lesions may not be psoriasis, but rather keratoderma blenorrhagicum.
17014005 Modest but sustained increase of serum high density lipoprotein cholesterol levels in pati 2006 Dec OBJECTIVE: Tumor necrosis factor-a (TNF-a) is a key cytokine in the pathogenesis of chronic inflammatory arthritides, has proatherogenic effects, and may be positively correlated with impairment of the action of insulin. Patients with chronic inflammatory arthritides have an increased risk for cardiovascular diseases. We assessed whether anti-TNF-a treatment modifies the unfavorable lipid profile induced by chronic inflammatory arthritides. METHODS: Sixty patients (24 with rheumatoid arthritis, 26 ankylosing spondylitis, and 10 psoriatic arthritis) receiving infliximab because of ongoing disease activity despite disease modifying drugs (DMARD) were prospectively studied for 6 months. Lipid profile, total cholesterol/high density lipoprotein cholesterol (TC/HDL-C), and low density lipoprotein cholesterol (LDL-C)/HDL-C ratios, as well as disease activity indices (DAS28 and BASDAI), were assessed. RESULTS: A sustained increase of serum HDL-C was observed [mean increase (95% CI)] 5 (3-7) mg/dl, 3.5 (1-6) mg/dl, and 3 (1-5) mg/dl at 1, 3, and 6 months, respectively (p < 0.01). Compared to nonresponders, HDL-C increased significantly more in EULAR or BASDAI responders (0.8 vs 5.8 mg/dl; p = 0.05). Serum TC was significantly increased [11 (4-8) mg/dl; p = 0.001] only after the first month of treatment. TC/HDL-C and LDL-C/HDL-C decreased only after the first month [0.3 (0.1-0.4), p < 0.01, and 0.2 (0.1-0.4), p < 0.01, respectively]. For patients with baseline LDL-C > 130 mg/dl, LDL-C/HDL-C decreased (p < 0.05) during the whole study period and TC/HDL-C decreased (p < 0.05) at 1 and 3 months. CONCLUSION: Anti-TNF-a treatment in patients with chronic inflammatory arthritides induces a modest, but sustained, increase in serum HDL-C levels, which may have a favorable effect in reducing the cardiovascular risk in these patients.
18537774 Utilization of biologic agents in rheumatoid arthritis in the United States: analysis of p 2008 BACKGROUND: Treatment of rheumatoid arthritis (RA) has shifted toward earlier and more aggressive therapy with tra- ditional disease-modifying antirheumatic drugs (DMARDs) and biologics. However, the extent to which these agents are used in current clinical practice in the United States (U.S.) has not been systematically evaluated. MATERIALS AND METHODS: This analysis of a large claims database assessed patterns of use of biologics within clinical practice in a broad U.S. population with RA. We identifed two cohorts of adults with RA using Thomson Healthcare MarketScan Research databases. Patients newly diagnosed with RA between 1999 and 2004 with 12 months or more of continuous enrollment prior to diagnosis and with 24 months or more post-diagnosis were included in one cohort. The second cohort included RA patients who appeared to be newly treated with biologic therapy and had continu- ous enrollment for 12 months or more prior to frst use of a biologic agent and 18 months or more following initial treatment. A total of 16,752 patients, newly diagnosed with RA, and 8218, new to biologics therapy, were included. RESULTS: Utilization of biologics increased from 3% of patients in 1999 to 26% in 2006. Patients initiated biolog- ics both as monotherapy (30%) and in combination with methotrexate (36%). Regimen modifcations were frequent, with a large percentage of patients requiring addition or subtraction of methotrexate. CONCLUSIONS: The use of biologics to treat RA is increas- ing, either as monotherapy or in combination with another DMARD. Modifcations to drug regimens are frequent and episodes are often of comparatively short duration.
17236286 Occurrence of self-reported systemic medical conditions in patients with periodontal disea 2006 OBJECTIVES: The objective of this retrospective study was to investigate the occurrence of self-reported systemic disorders in patients referred to a specialist clinic for periodontal treatment and to determine if an association existed between general health and periodontal disease severity in this population. MATERIAL AND METHODS: The study design was a case-controlled, retrospective chart review. Patient charts (n=1044) were selected from the Department of Periodontology, Carol Davila University of Medicine and Pharmacy. These charts were examined to determine patient's self-reported systemic condition. In addition, the periodontal diagnosis was recorded. Two examiners collected the data. One examiner abstracted patient's medical history from the standard clinic medical questionnaire. The second examiner assessed the radiographs and dental charts to determine the periodontal diagnosis. RESULTS: The most frequent disorders in patients with gingivitis were high blood pressure (35.85%), followed by coronary artery disease (15.741%), kidney and urinary tract disorders (15.71%) and allergic reactions (14.28%). 80% of patients with gingivitis had at least one of these disorders. The most frequent disorders in patients with periodontitis were high blood pressure (29.51%) followed by digestive disorders (18.92%), coronary artery disease (16.54%), kidney and urinary tract disorders (16.24%), endocrine disorders (10.58 %), rheumatoid arthritis/rheumatism (9.68%), Hepatitis A (9.38%), diabetes (8.79%) allergic reactions (8.79%), liver and gallbladder disorders (7.30%), sinusitis (6.55%), osteoporosis (5.51%) and respiratory disorders (5.36%). 81.96% of patients with periodontitis had at least one of these disorders. However, only rheumatoid arthritis was found to be more prevalent in periodontitis patients compared with gingivitis affected individuals (p<0.05). Multiple correlations were found between the independent variables. CONCLUSIONS: These findings support the results from previous investigators that a number of systemic conditions are closely associated with periodontal disease.
17179172 FCRL3 promoter 169 CC homozygosity is associated with susceptibility to rheumatoid arthrit 2007 Jun BACKGROUND: Human leucocyte antigen is the only genetic risk factor for rheumatoid arthritis (RA) that has been consistently observed in different populations. A number of other genes such as PTPN22 and PADI4 showed population-specific association with RA susceptibility. Recently, Fc receptor-like 3 (FCRL3) gene was found to be associated with RA susceptibility in Japanese, but with conflicting results in other populations. OBJECTIVE: To investigate the association of FCRL3 polymorphism with RA susceptibility and severity in Dutch Caucasian patients with RA, as well as to perform a meta-analysis to reveal the contribution of this gene to RA susceptibility. METHODS: A total of 931 Dutch RA cases and 570 unrelated Dutch controls were genotyped for four FCRL3 single-nucleotide polymorphisms (SNPs). Genotyping was performed using the MassArray matrix-assisted laser desorption ionisation-time-of-flight mass spectrometry. Association of the FCRL3 SNPs with susceptibility to RA was examined by single-marker, carrier and haplotype analysis. RESULTS: Carrier analysis of the SNP (rs7528684) revealed the association of CC genotype with a higher risk of developing RA as compared with TT and TC carriers (p = 0.039 and OR = 1.31). There was no significant difference in the genotype and allele frequencies of all investigated SNPs between cases and controls. Meta-analysis of all studies comparing 9467 individuals showed that the OR for the CC genotype to develop RA was 1.2 and the p value <0.001. CONCLUSION: A promoter polymorphism of FCRL3 (rs7528684) is associated with an increased risk of developing RA in Dutch Caucasians, suggesting that this association is relevant for RA in both Japanese and Caucasian populations.
17657707 Patient priorities of care in rheumatology outpatient clinics: a qualitative study. 2007 Dec OBJECTIVE: To provide more understanding of what rheumatoid arthritis (RA) patients want and need from an outpatient visit. METHODS: 25 patients who experienced care in a nurse practitioner clinic (n = 10), junior doctor clinic (n = 9) or consultant clinic (n = 6) in a large teaching hospital in West Yorkshire were interviewed about their perceptions and experiences of care. Interviews were approximately 1 1/2 hours in duration and were carried out in a neutral environment by a research nurse. Interview data were subjected to atheoretical content analysis, which resulted in the identification of emergent themes. RESULTS: Five main themes emerged from the analysis of interview data: 1) patients want to be communicated to clearly and effectively and value positive relationships with practitioners. These help to give patients confidence in the care they are receiving; 2) patients want to feel in control of their condition and tend to refuse interventions as a way of gaining control; 3) patients want to be given clear explanations during consultations, and want information in oral and written forms; 4) patients want to be able to access practitioners between scheduled appointments as a way of gaining reassurance; and 5) patients want to feel valued by society through having their difficulties appreciated and understood by others. CONCLUSION: This research adds to the body of evidence on what patients want from their rheumatology care, and each theme has clear implications for future practice.
17125526 Identification of novel citrullinated autoantigens of synovium in rheumatoid arthritis usi 2006 Recently, autoantibodies to some citrullinated autoantigens have been reported to be specific for rheumatoid arthritis (RA). However, an entire profile of and autoimmunity of the citrullinated proteins have been poorly understood. To understand the profile, we examined citrullinated autoantigens by a proteomic approach and further investigated the significance of citrullination in antigenicity of one of the autoantigens. Specifically, we detected citrullinated autoantigens in synovial tissue of a patient with RA by two-dimensional electrophoresis and Western blotting by using pooled sera from five patients with RA and anti-citrulline antibodies. After identifying the detected autoantigens by mass spectrometry, we investigated the contribution of citrullination to autoantigenicity by using a recombinant protein with or without citrullination on one of the identified novel citrullinated autoantigens. As a result, we found 51 citrullinated protein spots. Thirty (58.8%) of these spots were autoantigenic. We identified 13 out of the 30 detected citrullinated autoantigenic proteins. They contained three fibrinogen derivatives and several novel citrullinated autoantigens (for example, asporin and F-actin capping protein alpha-1 subunit [CapZalpha-1]). We further analyzed the contribution of citrullination to autoantigenicity in one of the detected citrullinated autoantigens, CapZalpha-1. As a result, frequencies of autoantibodies to non-citrullinated CapZalpha-1 were 36.7% in the RA group tested, 10.7% in the osteoarthritis (OA) group, and 6.5% in healthy donors. On the other hand, those to citrullinated CapZalpha-1 were 53.3% in the RA group, 7.1% in the OA group, and 6.5% in the healthy donors. This shows that autoantigenicity of citrullinated or non-citrullinated CapZalpha-1 is relevant to RA. The antibody titers to the citrullinated CapZalpha-1 were significantly higher than those to the non-citrullinated CapZalpha-1 in 36.7% of patients; however, the other patients showed almost equal antibody titers to both citrullinated and non-citrullinated CapZalpha-1. Therefore, the autoantibodies would target citrulline-related and/or citrulline-unrelated epitope(s) of CapZalpha-1. In conclusion, we report a profile of citrullinated autoantigens for the first time. Even though citrullination is closely related to autoantigenicity, citrullination would not always produce autoantigenicity in RA. Citrullinated and non-citrullinated autoantigens/autoepitopes would have different pathological roles in RA.
16484874 The potential use of antibacterial peptide antibody indices in the diagnosis of rheumatoid 2006 Feb BACKGROUND: Both rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are potentially disabling arthritic disorders for which as yet no highly sensitive and reliable diagnostic laboratory markers are available. OBJECTIVE: The objective of this study was to evaluate the levels of antibodies against Proteus and Klebsiella antigenic peptides in an endeavor to develop diagnostic indices for the identification of patients with RA and AS, respectively. METHODS: Sera from 50 patients with RA, 34 patients with AS, and 38 healthy subjects were screened for antibodies against "ESRRAL" and "IRRET" synthetic amino acid peptides obtained from Proteus hemolysin and urease (HU) as well as against "QTDRED" and "DRDE" peptides from Klebsiella nitrogenase and pullulanase (NP) proteins, respectively. Multiplication of the 2 antibodies against each organism produced indices for RA-HU and AS-NP. RESULTS: Significantly increased levels of anti-HU antibodies (P<0.0001) were observed in patients with RA when compared with patients with AS or with healthy control subjects. Patients with AS were found to have significantly elevated levels of anti-NP (P<0.0001) antibodies when compared with patients with RA or with healthy subjects. Furthermore, all patients with RA were found to have values of anti-HU antibody (RA-HU) index above 95% confidence limit (CL) of the mean of healthy control subjects; meanwhile, all patients with AS were having values of anti-NP antibody (AS-NP) index above the 95% CL of the mean of healthy control subjects (100% sensitivity). However, the specificity of the RA-HU index in RA and the AS-NP index in patients with AS were 92% and 95%, respectively. CONCLUSION: The use of the RA-HU or AS-NP diagnostic index as a sole marker or in combination with other autoantibody markers could be used in the identification of patients with RA or AS, respectively. Longitudinal investigations starting with patients with early disease will be needed.
16126800 An open label, single dose study to evaluate the safety, efficacy, and effects on CD25 exp 2006 Apr OBJECTIVE: To explore the safety, efficacy, and lymphocyte activation of a triple therapeutic regimen with infliximab, methotrexate (MTX), and ciclosporin A (CsA) by an open label, pilot study. PATIENTS AND METHODS: 19 patients (mean age 52.9 years) with active rheumatoid arthritis (mean DAS28 7.3) after a mean of 16.8 infliximab infusions and dose adjustments of both infliximab and MTX were enrolled. CsA was added to a stable therapeutic regimen. Disease activity was evaluated by the DAS28. Lymphocyte activation was evaluated by assessing CD25 expression on peripheral blood mononuclear cells (PBMCs). Primary end points were safety and efficacy according to the EULAR response criteria at 24 weeks. RESULTS: Eight patients (42%) discontinued treatment: adverse events (3), inefficacy (2) or non-compliance (2). One patient had a stroke and died. 5/11 (45%) patients who completed 24 weeks' treatment were moderate responders. CD25 expression, both on unstimulated and phytohaemagglutinin stimulated PBMCs in five patients assessed, was reduced (mean (SD) values from 37 (34)% to 15 (10)% and from 50 (15)% to 29 (20)%, respectively). CONCLUSION: In this group of patients with refractory, highly active disease, addition of CsA reduced lymphocyte activation, and resulted in a modest response and a high rate of discontinuation. In such patients, other new approaches need to be explored.