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ID PMID Title PublicationDate abstract
24515570 Association of higher methotrexate dose with lymphoproliferative disease onset in rheumato 2014 Sep OBJECTIVE: Methotrexate (MTX) is used as an anchor drug for rheumatoid arthritis (RA). Lymphoproliferative disease (LPD) occasionally develops in patients treated with MTX, and is known as MTX-associated LPD (MTX-LPD). Although MTX-LPD occurs mainly in RA patients, it has not been established if MTX administration is an independent risk factor for LPD in RA patients. We examined the clinical characteristics of MTX-LPD in Japanese RA patients and attempted to determine the risk factors for MTX-LPD development. METHODS: We performed a nested case-control study on RA patients. We enrolled 5,753 RA patients from Kagawa, Japan. In age- and sex-matched patients, we separated patients who did not develop LPD under MTX treatment (MTX non-LPD group) from those that did (MTX-LPD group) and conducted a comparative examination. We used multivariate analysis to determine the independent risk factors for MTX-LPD onset. RESULTS: There were 28 patients in the MTX-LPD group and 125 patients in the MTX non-LPD group. Multivariate analysis of the parameters extracted by univariate analysis revealed that the mean MTX dose was a risk factor for MTX-LPD after adjusting for age; therefore, higher MTX dose is associated with LPD onset in RA patients. CONCLUSION: MTX is an independent risk factor for LPD onset in Japanese RA patients.
23505920 Evaluation of status of arsenic, cadmium, lead and zinc levels in biological samples of no 2013 BACKGROUND: Arthritis is a chronic inflammatory disease resulting in inflammation of diarthrodial joints (particularly joints of hands, wrists, feet, knees, ankles, and shoulders), manifested by swelling and functional impairment. This study was designed to evaluate the levels of the toxic elements arsenic (As), cadmium (Cd), and lead (Pb) and correlate those with the essential trace element zinc (Zn) in biological samples (scalp hair, blood, and urine) of arthritis patients, in two age groups (46 - 60 and 61 - 75) of both genders. For comparison purposes all three biological samples were collected from gender- and age-matched non-arthritic subjects as referents. METHODS: The As, Cd, and Pb in biological samples were analysed by electrothermal atomic absorption spectrometry, prior to microwave assisted acid digestion. The level of Zn was determined by flame atomic absorption spectrometry. The validity and accuracy of the methodology was checked by using Certified Reference Materials (CRM) from the Community Bureau of Reference (BCR) of the Commission of the European Community and with those values obtained by conventional wet acid digestion method on the same CRMs. RESULTS: The results of this study showed that the mean values of As, Cd, and Pb were higher in blood, scalp hair, and urine samples of arthritis patients as compared to those values obtained in age-matched referent subjects. The concentration of Zn was lower in the biological samples of rheumatoid arthritis patients of both genders with respect to non-arthritic subjects. The urinary levels of the elements studied were found to be higher in the arthritis patients than in the age-matched healthy referents (p < 0.001). CONCLUSIONS: An inverse correlation was observed between Zn and toxic elements in biological samples of arthritis patients (r = 0.612 - 0.754). Intake of certain antioxidant micronutrients, particularly a zinc supplement, may protect against the development of rheumatoid arthritis.
24140642 TNF-like ligand 1A (TL1A) gene knockout leads to ameliorated collagen-induced arthritis in 2013 Dec 1 TNF-like ligand 1A (TL1A), also known as TNFSF15, is a member of the TNF superfamily. Its known receptor is death receptor 3 (DR3). In humans, TL1A also binds to a secreted TNF family member called decoy receptor 3, which interferes with the interaction between TL1A and DR3. TL1A/DR3 signal has been implicated in several autoimmune diseases in animal models as well as in clinical conditions. We generated TL1A gene knockout (KO) mice to assess its role in collagen-induced arthritis (CIA), a mouse model of human rheumatoid arthritis. The KO mice were fertile and had no visible anomalies. Their lymphoid organ size and cellularity, T and B cell subpopulations, Th cell and regulatory T cell development in vivo and in vitro, and antiviral immune responses were comparable to those of wild-type mice. However, the KO mice presented ameliorated CIA in terms of clinical scores, disease incidence, and pathological scores. The KO mice had reduced titers of pathogenic anti-collagen Abs in the sera. No apparent defect was found in the function of follicular Th cells. We revealed that plasma cells but not B cells expressed high levels of DR3 and were direct targets of TL1A. In the presence of TL1A, they survived better and produced more pathogenic Ab. This study presented novel knowledge about the role of TL1A in humoral immune responses and its mechanism of action in CIA pathogenesis.
25225991 The search for the missing 50-year-old gold. 2014 Oct Intramuscular and subcutaneous injections of foreign bodies have been used for a number of years for a variety of reasons, including medical and cosmetic purposes. The author describes a case of chronic wound complications secondary to intramuscular gold injections for the treatment of rheumatoid arthritis. The lesions were completely excised, the defect first treated with negative-pressure wound therapy, and, ultimately, split-thickness skin grafting with excellent functional result.
25224347 Safety of anti-tumor necrosis factor therapies in arthritis patients. 2014 PURPOSE: Inflammatory and rheumatic arthritis remain leading causes of disability worldwide. The arthritis therapeutic area commands the largest market for the prescription of biological and non-steroidal anti-inflammatory drugs (NSAID). Yet biotechnology and pharmaceutical companies conducting research and providing therapeutics in this area frequently face challenges in patient safety. The purpose of our study was to assess safety of anti-tumor necrosis factor therapies in arthritis patients. METHODS: The present study systematically reviews adverse events of biologicals alone or in the presence of NSAIDs and other immunosuppressant therapeutics such as disease-modifying antirheumatic drugs (DMARD). We assessed the rheumatology literature that included clinical trials with anti-tumor necrosis factor (TNF) biologicals and case reports published between 2010 and 2014. RESULTS: Currently approved anti-TNF biologicals in arthritis include the monoclonal antibodies infliximab, adalimumab, certolizumab pegol and golimumab, and the fusion protein etanercept. The most frequently-reported adverse event was infection. We grouped the adverse reactions as immune-mediated, hypersensitivity syndrome reactions including cutaneous and hepatic manifestation, neurological, hematological, and malignancy. DISCUSSION: Most adverse events are due to the failure of host immunological control, which involves susceptibility to the drug itself, or de novo infection or reactivation of a latent bacterial or viral infection, often with a different expression of disease. Drug-induced liver injury associated with anti-TNF biologicals must be kept in mind when evaluating patients with increased liver enzymes. CONCLUSION: Risk assessment in individuals undergoing treatment with biologicals represents a step towards achieving a personalized medicine approach to identify those patients that will safely benefit from this therapeutic approach. Patients and physicians must be alert of anti-TNF agents as potential causes of drug-induced liver injury and monitor the therapies. Personalizing therapeutic pharmacovigilance promises to optimize benefits while minimizing side effects.
23711100 Abatacept or infliximab for patients with rheumatoid arthritis and inadequate response to 2013 Jul OBJECTIVES: In the 1-year, double-blind, placebo-controlled ATTEST trial, efficacy of abatacept or infliximab versus placebo was reported in patients with rheumatoid arthritis (RA) and an inadequate response to methotrexate (MTX). The current study estimated trial-based and real-life costs of abatacept and infliximab for achieving pre-defined remission or low disease activity state (LDAS). METHODS: Quantity of drug, serious adverse event (SAE) rates and time (months) in remission or LDAS were taken from ATTEST for the trial-based calculation to derive a cost per remitting/LDAS patient and a cost per patient-month in remission/LDAS. Trial-based and real-life scenarios were performed. RESULTS: The annual trial-based costs per remitting/LDAS patient were €70.238/€37.208 for abatacept and €85.565/€46.602 for infliximab. In the first 6 months of the ATTEST trial, costs per patient-month in remission/LDAS were higher for abatacept (€11.024 and €6.018, respectively), relative to infliximab (€8.347 and €4.174, respectively). Over the full 12-month trial period cost per month in remission/LDAS estimates were only slightly in favour of infliximab (€6.959/€3.625) relative to abatacept (€7.297/€3.909). Assuming extension of treatment under real life conditions the cost per month in remission/LDAS turned substantially in favour of abatacept (€5.321/€2.819), as compared to infliximab (€7.189/€3.916). The higher initiation cost for abatacept to achieve remission/LDAS would be offset after a total 14.6 and 16.1 months of treatment, respectively, if treatment extended beyond 6 months under real-life conditions. These results proved to be robust when it was assumed that the (i) sharing of vials across patients completely averted infliximab wastage, (ii) AE risks were similar and (iii) onset of response was slower for abatacept. CONCLUSIONS: Our findings suggest a lower cost-consequence for abatacept during real-life treatment.
24687235 Pegylation of biological molecules and potential benefits: pharmacological properties of c 2014 Apr PEGylation of biological proteins, defined as the covalent conjugation of proteins with polyethylene glycol (PEG), leads to a number of biopharmaceutical improvements, including increased half-life, increased solubility and reduced aggregation, and reduced immunogenicity. Since their introduction in 1990, PEGylated proteins have significantly improved the management of various chronic diseases, including rheumatoid arthritis (RA) and Crohn's disease. Certolizumab pegol is the only PEGylated anti-tumour necrosis factor (TNF)-α agent. It is a PEGylated, humanised, antigen-binding fragment of an anti-TNF monoclonal antibody. Unlike other anti-TNF agents, it has no crystallisable fragment (Fc) domain. Because of its novel structure, certolizumab pegol may have a different mechanism of action to the other anti-TNF agents, and also has different pharmacodynamic properties, which could possibly translate to a different safety profile. Pharmacodynamic studies have shown that certolizumab pegol binds to TNF with a higher affinity than adalimumab and infliximab. Certolizumab pegol is also more potent at neutralising soluble TNF-mediated signalling than adalimumab and infliximab, and has similar or lesser potency to etanercept. Certolizumab pegol does not cause detrimental in vitro effects such as degranulation, loss of cell integrity, apoptosis, complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity. Certolizumab pegol may also penetrate more effectively into inflamed arthritic tissue than other anti-TNF agents, and is not actively transported across the placenta during pregnancy. Pharmacokinetic studies in healthy volunteers demonstrated that single intravenous and subcutaneous doses of certolizumab pegol had predictable pharmacokinetics. The pharmacokinetics of certolizumab pegol in patients with RA and Crohn's disease were consistent with pharmacokinetics in healthy volunteers.
23559613 Costs and benefits of routine histopathological examination of hammertoe specimens. 2013 Apr BACKGROUND: The purpose of this study was to evaluate the cost and benefit of routinely submitting hammertoe specimens for histopathological examination. We hypothesized that such examination rarely shows a new diagnosis and seldom alters postoperative care. MATERIALS AND METHODS: Three hundred and fourteen proximal interphalangeal (PIP) joint and 37 extensor tendon specimens from 187 consecutive hammertoe correction surgeries were submitted by 2 surgeons for histopathological examination between January 2009 and December 2011. Each patient's chart was reviewed to determine whether the histopathological examination revealed a diagnosis other than degenerative joint or degenerative tendon and whether subsequent patient management was altered. The total reimbursements for professional charges were calculated using the average reimbursement from common insurance providers for two Current Procedural Terminology (CPT) codes: 88304 (soft tissue examination) and 88311 (decalcification). RESULTS: Almost all of the specimens were diagnosed as degenerative: 97.5% (307/314) of the PIP specimens and all (37/37) of the tendon specimens. Seven PIP specimens (2.2%, 7/314) from 5 patients (2.7%, 5/187) and no tendon specimens had other diagnoses. These diagnoses were rheumatoid arthritis (5/314, 1.6%), osteomyelitis (1/314, 0.3%), and pigmented villonodular synovitis (PVNS) (1/314, 0.3%). Only the PVNS was a new diagnosis. A total of $56,750 was spent to determine 1 new diagnosis. CONCLUSION: The routine submission of hammertoe specimens for pathological evaluation was not cost-efficient. Our analysis showed that new diagnoses were rarely found and patient management was not affected.
25155581 Modulation of autoimmune rheumatic diseases by oestrogen and progesterone. 2014 Dec Sexual dimorphism is evident in the risk and expression of several human autoimmune diseases. Differences in disease manifestations observed between sexes are likely to involve immunomodulation by sex steroids, nonhormonal factors encoded by genes on the X and Y chromosomes, and immunological phenomena unique to pregnancy. In systemic lupus erythematosus (SLE), and perhaps other autoantibody-mediated diseases, oestrogen seems to increase the risk of disease in genetically predisposed women by targeting key immune pathways, including the type 1 interferon (IFN) response, differentiation of CD4(+) T helper cells and survival of autoreactive B cells. By contrast, progesterone seems to reduce the risk of SLE by counteracting the effects of oestrogen on some of these same pathways, which suggests that the balance between oestrogen and progesterone can determine disease expression. In this Review we focus on the roles of the sex steroid hormones oestrogen and progesterone in modulating the risk and expression of SLE and rheumatoid arthritis. Intensive research in this area promises to identify novel therapeutic strategies and improve understanding of the immunological requirements and complications of pregnancy, and is expected to define the mechanisms behind sexual dimorphism in autoimmunity, immunity and other aspects of human health--a newly announced directive of the NIH.
23063175 Model of excellence in Rheumatology Day Hospitals in Spain: the HD-Reumatolex project. 2013 May OBJECTIVES: Biologics have shown greater efficacy than traditional treatments in patients with rheumatoid arthritis, although some cannot be administered on an outpatient basis. Day hospitalization requires the patient to attend the hospital for a few hours to receive those treatments that cannot be administered on an outpatient basis or that do not justify admission to hospital. Few studies have analyzed the situation of Rheumatology Day Hospitals (RDH) in Spain. The HD-Reumatolex project aims to evaluate the situation of Spanish RDHs in terms of strategy, training, management, and quality of care. MATERIAL AND METHODS: The project was based on a "model of excellence in RDH" design, which made it possible to perform a comparative analysis (benchmarking) of 21 Rheumatology Departments. The 19 criteria evaluated were divided into 3 categories: Strategic processes, Key processes, and Support processes. RESULTS: The lowest mean scores were recorded for follow-up of clinical practice guidelines/recommendations and existence of a quality plan (Strategic processes), criteria for training among RDH professionals (Support processes), and admission and discharge (Key processes). Five RDH achieved the benchmark when the position obtained by the RDH in Key processes was plotted against the one obtained in Strategic processes and Support processes. One RDH emerged as a clear leader in the comparison. CONCLUSIONS: None of the RDH obtained the total maximum score at the category level or at the total results level, thus revealing room for improvement in the attainment of excellence for all the participating centers.
24680117 [Severe hypercalcemia revealing sarcoidosis precipitated by etanercept]. 2014 Mar INTRODUCTION: The principal secondary effects of anti-TNF alpha therapy are now well understood, particularly the risk of opportunistic infections. Other paradoxical effects have been described much more occasionally such as the developement of sarcoid-like granulomatous reactions. CASE REPORT: We report here the case of a woman of 39 years treated for severe rheumatoid arthritis for five years with etanercept. She was admitted to hospital as an emergency with vomiting and diffuse abdominal pain. Investigations revealed severe hypercalcaemia and acute renal failure. After correction of the metabolic disturbances with rehydration and biphosphonates, CT scanning of the abdomen, pelvis and thorax showed bilateral interstitial infiltration and splenomegaly. The diagnosis of sarcoidosis was confirmed by endoscopic bronchial biopsies. Progress was satisfactory following withdrawal of the etanercept and corticosteroid therapy in reducing dosage. CONCLUSION: The risk of induced sarcoidosis should be understood in patients receiving anti-TNF therapy and should be considered in cases of hypercalcaemia and/or splenomegaly.
25744639 [Microbiota and autoimmunity]. 2014 The microbiota plays a fundamental role in the development and the maintenance of the host immune system. Since microbiota is important in the induction and the expansion of Th17 cells and regulatory T cells, growing evidence supports that microbiome affect the induction and the disease course of autoimmune disorders. In this review, we describe the recent studies on the involvement of microbes in animal models of autoimmune diseases such as rheumatoid arthritis (RA) and multiple sclerosis (MS) using germ-free conditions, antibiotics treatment and gnotobiotic mice. Furthermore, we introduce the studies on analysis of microbiota in human autoimmune diseases including RA and MS.
24288575 Robust joint analysis with data fusion in two-stage quantitative trait genome-wide associa 2013 Genome-wide association studies (GWASs) in identifying the disease-associated genetic variants have been proved to be a great pioneering work. Two-stage design and analysis are often adopted in GWASs. Considering the genetic model uncertainty, many robust procedures have been proposed and applied in GWASs. However, the existing approaches mostly focused on binary traits, and few work has been done on continuous (quantitative) traits, since the statistical significance of these robust tests is difficult to calculate. In this paper, we develop a powerful F-statistic-based robust joint analysis method for quantitative traits using the combined raw data from both stages in the framework of two-staged GWASs. Explicit expressions are obtained to calculate the statistical significance and power. We show using simulations that the proposed method is substantially more robust than the F-test based on the additive model when the underlying genetic model is unknown. An example for rheumatic arthritis (RA) is used for illustration.
22994412 Anti-arthritic effects of clematichinenoside (AR-6) on PI3K/Akt signaling pathway and TNF- 2013 Jan CONTEXT: Clematichinenoside (AR-6) is a triterpene saponin from an anti-arthritic herbal formula Wei-Ling-Xian in Chinese, which is an herbal medicine derived from the dried root and rhizome of Clematis chinensis Osbeck, C. hexapetala Pall., or C. manshurica Rupr. (Ranunculaceae). OBJECTIVE: To investigate the modulating effect and explored the potential mechanism of AR-6 in rheumatoid arthritis (RA), using collagen-induced arthritis (CIA) in a rat model. MATERIALS AND METHODS: CIA was evaluated by measuring body weight, paw swelling and organ index. Expression of TNF-α, PI3K and p-Akt in synovium tissue was measured by immunohistochemistry. Furthermore, expression of TNF-α mRNA, PI3K mRNA and p-Akt mRNA was measured with RT-PCR. RESULTS: The intragastric administration of AR-6 (32, 16 and 8 mg/kg), especially the high dose level of 32 mg/kg, significantly suppressed the swelling of hind paws of CIA rats (p < 0.01) and inhibited their body weight loss (p < 0.01). Based on histopathological observation, all AR-6 groups showed great amelioration compared with model group. Moreover, AR-6 significantly reduced the production of TNF-α, PI3K and p-Akt expression by immunohistochemistry (p < 0.01), and decreased TNF-α mRNA, PI3K mRNA and p-Akt mRNA in CIA rat synovium (p < 0.01). DISCUSSION: Our study indicates the mechanism of AR-6 is associated with PI3K/Akt signaling pathway and TNF-α. CONCLUSIONS: Such characteristics relating to AR-6 curing chronic inflammation of CIA, may be effectively applied to the therapeutic potential in patients with inactive RA.
24074008 Costs of tumor necrosis factor blockers per treated patient using real-world drug data in 2013 Oct BACKGROUND: Several anti-inflammatory biologic medications are available in the United States for the treatment of moderate-to-severe rheumatoid arthritis, moderate-to-severe psoriasis, psoriatic arthritis, or ankylosing spondylitis. The tumor necrosis factor (TNF) blockers etanercept, adalimumab, and infliximab are approved for use in adults with any of these conditions, but predicting the annual costs of TNF-blocker treatment is complex due to differences in dosing schedules, treatment gaps, switching between TNF blockers, and dose escalation over time. OBJECTIVES: To estimate the annual cost per treated patient from the payer perspective for etanercept, adalimumab, or infliximab in adults with rheumatoid arthritis, psoriasis, psoriatic arthritis, or ankylosing spondylitis. METHODS: Adults in the IMS LifeLink Health Plan Claims Database were analyzed if they had at least 1 claim for etanercept, adalimumab, or infliximab between February 1, 2008, and July 5, 2010, and were continuously enrolled for at least 180 days before (pre-index period) through 360 days after the index claim (the first TNF-blocker claim after 6 months of continuous enrollment in the study period). Patients had a diagnosis of rheumatoid arthritis, psoriasis, psoriatic arthritis, or ankylosing spondylitis, or a combination of these conditions, in the pre-index period. Cost was based on dose and price using April 2012 wholesale acquisition cost. Costs of administration were included for the first subcutaneous dose (etanercept or adalimumab) for new patients and for every intravenous dose (infliximab). Total TNF-blocker drug and administration costs, including nonindex TNF-blocker costs among patients who switched treatments, were divided by number of patients to yield cost per treated patient for each index TNF blocker. Subgroup analyses included cost by condition and cost for patients who were new to TNF-blocker treatment (no index TNF-blocker claim in the pre-index period) or continuing TNF-blocker treatment. RESULTS: Of the 30,107 patients in the analysis, the majority received etanercept (15,488 patients; 51.4%), followed by adalimumab (8,959 patients; 29.8%) and infliximab (5,660 patients; 18.8%). Approximately 2 in 3 patients (18,897 patients) were continuing TNF-blocker treatment, including 66.0%, 52.6%, and 70.0% of patients in the etanercept, adalimumab, and infliximab groups, respectively. Across all indications, the annual TNF-blocker cost per treated patient was lowest for etanercept, followed by adalimumab and then infliximab, respectively: overall ($17,767, $19,272, and $24,273); new patients ($17,270, $17,959, and $21,482); and continuing patients ($18,203, $20,453, and $25,468). Cost by condition among all patients ranged from $14,838 to $20,251 for etanercept, from $18,051 to $20,233 for adalimumab, and from $22,939 to $28,519 for infliximab. Cost by condition was 3% to 31% greater for adalimumab than for etanercept (relative cost, 103% to 131%), except among patients with psoriasis (relative cost, 94%), and was 26% to 72% greater for infliximab than for etanercept (relative cost, 126% to 172%). Approximately 9% to 11% of patients in each group switched TNF blockers in the first year, and the costs of nonindex TNF blockers comprised 16.8% of the total cost for etanercept, 13.4% for adalimumab, and 6.9% for infliximab. CONCLUSIONS: In adult patients with rheumatoid arthritis, psoriasis, psoriatic arthritis, or ankylosing spondylitis, or some combination of these conditions, etanercept had a lower cost per treated patient than adalimumab or infliximab, except in patients with psoriasis alone. In these patients, adalimumab had a lower cost per treated patient than etanercept or infliximab.
25556066 A LC-ESI-MS method for the simultaneous determination of madecassoside and its metabolite 2014 Dec To develop a simple and highly sensitive high performance liquid chromatography with electrospray ionization mass spectrometric (LC-ESI-MS) method for the simultaneous determination of madecassoside and its major metabolite madecassic acid in rat plasma, and compare the pharmacokinetics of the two compounds in normal and collagen-induced arthritis (CIA) rats. Glycyrrhetinic acid was used as the internal standard (IS). Chromatographic separation was accomplished on an Inertsil ODS-3 column, using a gradient elution with the mobile phase composed of acetonitrile and water acidified with 0.1% (V/V) formic acid. Detection was achieved by ESI-MS under the negative selected ion monitoring (SIM) mode. In normal and CIA rats, madecassoside (30 mg·kg(-1)) was orally administered for 21 consecutive days from the day of arthritis onset. For madecassoside, the linear range was 10-1 000 ng·mL(-1) with the square regression coefficient (r) of 0.998 9, while for madecassic acid, the linear range was 10-500 ng·mL(-1) with the square regression coefficient (r) of 0.996 1. The lower limit of quantification was 10 ng·mL(-1) for both analytes. The intra- and inter-day precision ranged from 1.78% to 13.42% for madecassoside and 2.30% to 14.90% for madecassic acid, and the accuracy was between -0.95% and 6.30% for madecassoside and between -1.48% and 5.34% for madecassic acid. The average recoveries of madecassoside, madecassic acid and IS from spiked plasma samples were > 81%. The developed method was successfully applied to the pharmacokinetic study of madecassoside and madecassic acid in rats after an oral administration of madecassoside. During initial 7 days of dosing, the cmax and AUC of madecassoside were greatly decreased and Vd/F was markedly increased in CIA rats, and no significant difference was observed on the first day of dosing. In contrast, the T1/2, cmax and AUC of madecassic acid were significantly increased, and Ke of madecassic acid was greatly decreased in CIA rats compared with normal rats. Along with repeated administration of madecassoside, the differences of pharmacokinetic parameters of both madecassoside and madecassic acid between CIA and normal rats gradually subsided. The pharmacokinetic characteristics of both madecassoside and madecassic acid in rats were significantly altered by arthritis status, and the differences of pharmacokinetic parameters between arthritis and normal rats coincide with the severity of arthritis.
24617049 High IL-23 level is a marker of disease activity in rheumatoid arthritis. 2013 Rheumatoid arthritis (RA) is a chronic autoimmune systemic disorder characterized by inflammatory responses mainly affecting the synovial joints. Interleukin-23 (IL-23) is a heterodimeric pro-inflammatory cytokine secreted by activated dendritic cells and activated macrophages. IL-23 is the key cytokine controlling inflammation in peripheral tissues leading to the development of autoimmune diseases. The objective of our study was to determine the relationship between the IL-23 level and disease activity in RA patients. Sixty RA patients were included in the study with mean age of 40 years; they included 44 (73.3 %) females and 16 males (26.7 %). The clinical parameters of disease activity were determined, including the 28-joint disease activity score (DAS28), serum levels of C-reactive protein (CRP), Anti-citrullinated peptide antibody (ACPA), rheumatoid factor (RF), and TNF-alpha and the degree of bony erosions based on X-rays. Patients were subdivided into active disease group (n = 30) with DAS28 score higher than 5.1 (Group I); and remission group (n = 30) with DAS28 score less than 2.6 (Group II). Thirty healthy individuals in the same age group of RA patients including 22 (73.3%) females and 8 males (26.7%) were randomly selected as the control group (Group III). The levels of IL-23 were determined by enzyme-linked immunosorbent assay (ELISA) and the correlations between the serum levels of IL-23 and disease activity parameters of patients with RA were determined. Serum levels of IL-23 were significantly higher in RA patients during active stage of the disease in comparison to the patients in remission and the control group. There was a significant positive correlation between serum IL-23 levels in RA patients and individual disease activity parameters. It is concluded that elevated serum IL-23 level may be a useful marker to detect active RA and disease progression in patients with RA.
23994256 Chemokine and cytokine levels in osteoarthritis and rheumatoid arthritis synovial fluid. 2013 Oct 31 To develop a method of the assay of chemokine and cytokine signaling in synovial fluid from patients suffering from osteoarthritis (OA) or rheumatoid arthritis (RA) and evaluate the effect of heterophilic antibodies on the reliability of the data. 21 synovial fluid samples from OA and 16 synovial fluid samples from RA patients were analyzed using a unique 2 step dot sandwich ELISA based micro-well protein array designed to detect heterophilic antibody signaling in the presence or absence of an effective heterophilic blocking reagent with assays carried out for Eotaxin, hGROa, interleukin (IL)-8, IP10, MCP-1, MCP-2, MIG, RANTES, TARC and IL-6. Array analysis reveals that the selective presence of heterophilic antibodies interferes with the accurate assay of synovial fluid samples from a minority of RA patients but not OA synovia. Using a commercial blocking diluent OA and RA synovial fluids reveal significant differences in chemokine content (IL-6, Eotaxin, hGROa, MCP-2, MIG, TARC, IL-8, RANTES). Using a two-step assay protocol it is possible to readily detect inappropriate antibody signaling due to heterophilic antibodies and devise a protocol designed to eliminate this problem thereby more accurately quantify cytokines and chemokines specific to both RA and OA fluids.
23852762 Cardiovascular risk stratification in rheumatic diseases: carotid ultrasound is more sensi 2013 Nov OBJECTIVE: To determine the ability of Coronary Artery Calcification Score (CACS) and carotid ultrasonography in detecting subclinical atherosclerosis in rheumatoid arthritis (RA). METHODS: A set of 104 consecutive RA patients without history of cardiovascular (CV) events were studied to determine CACS, carotid intima-media thickness (cIMT) and plaques. Systematic Coronary Risk Evaluation (SCORE) modified according to the EULAR recommendations (mSCORE) was also assessed. RESULTS: The mean disease duration was 10.8 years, 72.1% had rheumatoid factor and/or anti-CCP positivity and 16.4% extra-articular manifestations. Nine were excluded because they had type 2 diabetes mellitus or chronic kidney disease. CV risk was categorised in the remaining 95 RA patients according to the mSCORE as follows: low (n=21), moderate (n=60) and high/very high risk (n=14). Most patients with low mSCORE (16/21; 76.2%) had normal CACS (zero), and none of them CACS>100. However, a high number of patients with carotid plaques was disclosed in the groups with CACS 0 (23/40; 57.5%) or CACS 1-100 (29/38; 76.3%). 72 (75.8%) of the 95 patients fulfilled definitions for high/very high CV as they had an mSCORE ≥5% or mSCORE <5% plus one of the following findings: severe carotid ultrasonography findings (cIMT>0.9 mm and/or plaques) or CACS>100. A CACS>100 showed sensitivity similar to mSCORE (23.6% vs 19.4%). In contrast, the presence of severe carotid ultrasonography findings allowed identifying most patients who met definitions for high/very high CV risk (70/72; sensitivity 97.2% (95% CI 90.3 to 99.7)). CONCLUSIONS: Carotid ultrasonography is more sensitive than CACS for the detection of subclinical atherosclerosis in RA.
23750028 Immunology and bone. 2013 Jul It is now well acknowledged that the immune and skeletal systems interact and affect one another during developmental physiology and pathology. With the aid of modern conditional gene targeting and transgenic technologies, this field of interdisciplinary research, known as osteoimmunology, is rapidly advancing. Numerous bone phenotypes have been described in immune-compromised gene-deficient mice and, albeit to a lesser extent, immune deficiencies exist in osteo-compromised gene-deficient mice, suggesting that bone cells themselves actually regulate the development of immune cells directly. In this review, I discuss the essential role of key cytokines, signalling transduction pathways and transcription factors during immune and bone development, and how pathology driven dysregulation of these shared mechanisms can lead to clinical manifestations. Diseases that are within the remit of osteoimmunology continue to cause significant morbidity, for example, rheumatoid arthritis, osteoporosis, multiple myeloma and breast/prostate cancer. The complexity and overlapping cellular and molecular interactions between the immune and bone tissues, mean that despite fervent research of these diseases, it remains a major challenge to discover therapeutics that can specifically target one system without detrimentally affecting the other.