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ID PMID Title PublicationDate abstract
24627057 [Treatment of rheumatoid arthritis in the Brazilian Unified National Health System: expend 2014 Feb This study aimed to characterize the profile of users and related expenses with infliximab and synthetic disease-modifying anti-rheumatic drugs (DMARD) for rheumatoid arthritis treatment in the Brazilian Unified National Health System (SUS). We constructed a cohort from 2003 to 2006 drawing on databases of the SUS Outpatient Information System. Analyses were stratified by clinical and socio-demographic characteristics. We calculated average monthly expenditure per individual follow-up year and the factors that influenced it. The cohort consisted of 26,228 patients, mostly female, between 40 and 59 years of age, living in the Southeast of Brazil, and diagnosed with Felty's syndrome. Medicines for rheumatoid arthritis totalized BRL 74,306,087.18, of which infliximab accounted for 70%. Median monthly per capita expenditure was BRL 3,466.03 for patients receiving infliximab compared to BRL 143.85 for patients treated with synthetic DMARD. Drug treatment for rheumatoid arthritis was the main expense in SUS, with high economic impact from infliximab. Sex, diagnosis, age, and region of residence were factors that influenced expenditures.
25112484 The association between vibration and vascular injury in rheumatic diseases: a review of t 2015 Feb Vascular manifestations can be seen early in the pathogenesis of inflammatory rheumatic diseases. Animal experiments, laboratory and clinical findings indicated that acute or long-term vibration exposure can induce vascular abnormalities. Recent years, in addition to Raynaud's phenomenon (RP), vibration as a risk factor for other rheumatic diseases has also received corresponding considered. This review is concentrated upon the role of vibration in the disease of systemic sclerosis (SSc). In this review, we are going to discuss the main mechanisms which are thought to be important in pathophysiology of vascular injury under the three broad headings of "vascular", "neural" and "intravascular". Aspects on the vibration and vascular inflammation are briefly discussed. And the epidemiological studies related to vibration studies in SSc and other rheumatic diseases are taken into account.
25347903 [Inflammatory myopathy with initial respiratory muscles involvement and rheumatoid arthrit 2014 Inflammatory myopathies comprise a heterogeneous group of subacute, chronic and sometimes acute acquired muscle diseases. The most common inflammatory myopathies seen in practice can be separated into four distinct subsets: polymyositis, dermatomyositis, necrotizing autoimmune myositis and inclusion body myositis. These disorders present as proximal and symmetric muscle weakness but rarely respiratory muscles may also be affected. We report the case of a 39 year-old female with inflammatory myopathy with acute respiratory failure due to alveolar hypoventilation secondary to respiratory muscle dysfunction that required mechanical ventilation. The treatment with steroids, methotrexate and intravenous immune globulin was successful as well as the implementation of non-invasive ventilation as an alternative to endotracheal intubation.
24886363 Hyperuricaemia: a marker of increased cardiovascular risk in rheumatic patients: analysis 2014 May 23 BACKGROUND: Gout and hyperuricaemia may be associated with increased cardiovascular risk, but analyses in different populations show conflicting results. This study investigates the impact of serum uric acid, inflammation and traditional CV risk parameters on CV event risk in patients with gouty arthritis and patients with non-gouty rheumatic disease. METHODS: cross-sectional and prospective multivariate analysis of the relation between tertiles of serum uric acid and individual traditional CV risk factors in a cohort of gouty arthritis (GA, n=172), rheumatoid arthritis (RA, n=480) and osteoarthritis (OA, n=206) patients. MAIN OUTCOME MEASURES: systolic blood pressure, TC/HDL ratio, GlyHb, BMI and first CV events. RESULTS: Individual CV risk factors were significantly less favourable in GA (systolic blood pressure, TC/HDL ratio, BMI, p<0.05). In RA and OA, but not in GA, individual cardiometabolic parameters correlated with serum uric acid values (OA: RA: systolic blood pressure, TC/HDL ratio, BMI; systolic blood pressure, TC/HDL ratio, GlyHb, BMI; p<0.05). In non-GA individuals the highest tertile of serum uric acid (>0.34 mmol/L) and NT proBNP level were independent predictors of first CV events, against age and GlyHb level in GA (p<0.05). The hazard of first CV events was equally significantly increased in GA patients (HR 3.169, 95% CI 1.287-7.806) and non-GA individuals with a serum uric acid ≥ 0.34 mmol/L (HR 3.721, 95% CI 1.603-8.634) compared to non-GA individuals with a serum uric acid < 0.27. CONCLUSIONS: GA is associated with a 3.1-fold hazard of first CV events. In non-GA rheumatic patients increasing serum uric acid is associated with increased CV risk, whereas CV risk in GA is independent of serum uric acid values. The presence of GA or a baseline serum uric acid in the upper range are possibly stronger predictors of first CV events than some traditional CV risk factors or parameters of inflammation.
23440377 [Methotrexate as combination partner of TNF inhibitors and tocilizumab: what is reasonable 2013 Apr BACKGROUND: The prognosis of rheumatoid arthritis has been substantially improved by the treatment with biologics; however, it is still unclear which combination of biological and conventional disease-modifying antirheumatic drugs (DMARDs) is optimal to achieve remission as in clinical trials biologics were mainly studied in combination with methotrexate or as monotherapy. There are, however data that the efficacy of tumor necrosis factor (TNF) inhibitors is better in combination with methotrexate, whereas the efficacy of tocilizumab is optimal even as a monotherapy. In this article the differing dependence of TNF inhibitors and of tocilizumab on the combination with methotrexate is explained from the viewpoint of an immunologist. METHODS: A selective search and evaluation of the literature were carried out in relation to the mechanism of action of TNF inhibitors, tocilizumab and methotrexate in rheumatoid arthritis. RESULTS AND CONCLUSIONS: Methotrexate mainly targets the activation of T and B lymphocytes and TNF inhibitors suppress monocytes and myeloid dendritic cells. Tocilizumab corrects the errant activation and differentiation of T and B lymphocytes and in addition inhibits monocytes, dendritic cells and neutrophils. Therefore, TNF inhibitors and methotrexate act optimally only in combination to exert an effect on all components of the cellular immune system in rheumatoid arthritis. In contrast, tocilizumab has a broad mode of action even in monotherapy.
25249238 Systematic review and meta-analysis of effects of foot orthoses on pain and disability in 2015 PURPOSE: This meta-analysis examined the effects of foot orthoses (FO) on pain and disability in rheumatoid arthritis (RA) patients. METHODS: MEDLINE, Cochrane Controlled Trials Register, EMBASE, SPORT Scielo, and CINAHL were searched through July 2014 for randomized controlled trials (RCTs) examining the effects of orthoses on pain and disability in RA patients. Two reviewers selected studies independently. Weighted mean differences (WMDs) and 95% confidence intervals (CIs) were calculated, and heterogeneity was assessed using the I(2) test. RESULTS: Three studies, involving 110 patients who received FO and 108 control patients, met the study criteria. Relative to controls, FO had a positive impact on pain (WMD 0.40; 95% CI 0.04-0.57). Between group differences in disability were not statistically significant. CONCLUSIONS: FO may improve pain in RA patients, but their impact on disability remains undetermined. Additional large RCTs are needed to investigate the effects of these devices in RA patients. Implications for Rehabilitation The use of foot orthoses (FO) often part of the conservative treatment of patients with rheumatoid arthritis (RA). However, the indication of these devices is usually empiric. Thus, the results of this meta-analysis can provide guidance to rehabilitation professionals to undertake these devices to therapeutic programs. There is no consensus among rehabilitation professionals regarding the efficacy of FO improved pain and disability in patients with RA. The results of this meta-analysis suggest that the use of the FO improves pain but has no impact on disability. Thus, rehabilitation professionals, from reading this article will make clear to their patients that benefit of the FO is exclusively in pain improvement. Healthcare professionals and organizations should take into account the costs of production of FO during the definition of the therapeutic program. In case of low cost, the effect on improvement of pain in the feet can justify the indication of these devices to a patient with RA.
22949223 Abatacept and reduced immune response to pandemic 2009 influenza A/H1N1 vaccination in pat 2013 Mar OBJECTIVE: To evaluate the influence of abatacept (ABA) and associated contributing factors on pandemic 2009 influenza A/H1N1 vaccine immunogenicity in rheumatoid arthritis (RA) patients. METHODS: The response to a nonadjuvanted monovalent pandemic 2009 influenza A/H1N1 killed virus vaccine was analyzed in 11 RA patients using ABA (RA-ABA), most with concomitant nonbiologic disease-modifying antirheumatic drugs (DMARDS), and compared to 33 age-matched RA patients on methotrexate (MTX) and 55 healthy controls, all without previous seroprotection. Clinical and laboratory evaluations were performed before and 21 days after vaccination. Anti-influenza antibody titers were measured by hemagglutination inhibition assay. Seroprotection (antibody titers ≥1:40) and the factor increase (FI) in the geometric mean titers (GMTs) were calculated. Prevaccination lymphocyte counts and gammaglobulin levels were determined. RESULTS: Sex distribution, disease duration, and the Disease Activity Score in 28 joints were similar in the RA groups (P > 0.05). After vaccination, seroprotection was significantly reduced in RA-ABA patients compared to RA-MTX patients (9% versus 58%; P = 0.006) and controls (69%; P ≤ 0.001). FI-GMT was severely reduced in RA-ABA patients compared to RA-MTX patients (1.8 [1.4-2.3] versus 8.7 [5.2-17.4]; P < 0.001) and controls (11.5 [8.0-16.7]; P ≤ 0.001). Lymphocyte counts were comparable in RA groups (P > 0.05), but RA-ABA patients had slightly lower gammaglobulin levels than RA-MTX patients (0.9 gm/dl [0.6-1.8] versus 1.2 gm/dl [0.8-1.7]; P = 0.03), although almost all were within the normal range values. CONCLUSION: The current study established that ABA, in association with traditional DMARDs, significantly reduces the humoral response to pandemic 2009 influenza A/H1N1 vaccine in RA patients. The results suggest an influence of costimulatory modulation in humoral response to this vaccine.
23453476 Prospective assessment of bone texture parameters at the hand in rheumatoid arthritis. 2013 Oct OBJECTIVE: Fractal bone analysis (Hmean) is a texture parameter reflecting bone microarchitecture. The BMA device (D3A™ Medical Systems, Orléans, France) is a high-resolution X-ray device that allows assessment of bone texture analysis. We aimed to measure Hmean in rheumatoid arthritis patients at the second and third metacarpal bones, at baseline and after 1 year of follow-up, and to assess the relationship of Hmean and rheumatoid arthritis disease parameters. METHODS: Patients with rheumatoid arthritis according to ACR criteria were included. They were assessed over 1 year, in the context of a prospective study conducted in Maastricht. For this substudy, activity of the disease was assessed by erythrocyte sedimentation rate, C-reactive protein and Disease Activity Score 28 performed at each visit. Radiographic bone damage was assessed using hand and feet radiographs at baseline and on a 1-year basis. The bone texture parameters were evaluated on the second and third metacarpal heads of the left hand using BMA device. RESULTS: One hundred and sixty-five rheumatoid arthritis patients were included in this study. At baseline, Hmean was negatively correlated with age [r=-0.22 (P=0.013)] and erythrocyte sedimentation rate [r=-0.16 (P=0.039)]. No significant correlation was found between Hmean and Disease Activity Score, disease activity Visual Analog Scale, daily corticosteroid dose and C-reactive protein. There was a significant increase in Hmean of second and third metacarpal bones over 1 year (1.6% and 1.3%, P<0.01) except in patients with local second and third metacarpal bones erosion. CONCLUSION: The bone texture parameter Hmean is influenced by age, inflammation and local erosions in rheumatoid arthritis.
24605340 Proteoglycan aggrecan conducting T cell activation and apoptosis in a murine model of rheu 2014 Rheumatoid arthritis (RA) is a systemic autoimmune disease and its targeting of the joints indicates the presence of a candidate autoantigen(s) in synovial joints. Patients with RA show immune responses in their peripheral blood to proteoglycan (PG) aggrecan. One of the most relevant animal models of RA appears to be proteoglycan-induced arthritis (PGIA), and CD4(+) T cells seem to play a crucial role in the initiation of the disease. In this review, the role of various T cell epitopes of aggrecan in the induction of autoreactive T cell activation and arthritis is discussed. We pay special attention to two critically important arthritogenic epitopes, 5/4E8 and P135H, found in the G1 and G3 domains of PG aggrecan, respectively, in the induction of autoimmune arthritis. Finally, results obtained with the recently developed PG-specific TCR transgenic mice system showed that altered T cell apoptosis, the balance of activation, and apoptosis of autoreactive T cells are critical factors in the development of autoimmunity.
24489016 Association of rheumatoid arthritis susceptibility gene with lipid profiles in patients wi 2014 Jun OBJECTIVE: RA patients have an increased risk of cardiovascular (CV) disease, although the mechanisms are unclear. As RA and CV disease may be associated through lipid profiles, we examined whether single nucleotide polymorphisms (SNPs) associated with RA susceptibility were associated with low-density lipoprotein (LDL), high-density lipoprotein (HDL) and triglyceride (TG) levels in RA subjects. METHODS: Patients (n = 763) enrolled in the Veterans Affairs RA registry who were not on hydroxymethylglutaryl-CoA reductase inhibitor were genotyped for human leukocyte antigen shared epitope (HLA-DRB1-SE) and SNPs in the following genes: CTLA-4 (cytotoxic T-lymphocyte antigen 4), IL-10, PTPN22 (protein tyrosine phosphatase, non-receptor type 22), REL (c-Rel), STAT4 (signal transducer and activator of transcription protein), TNF- and TRAF1 (TNF receptor-associated factor 1). Other covariates included patient characteristics (age, gender, race, smoking status, education, BMI, modified CharlsonDeyo comorbidity index), CV characteristics (hypertension, diabetes, alcohol abuse), pharmacologic exposures (MTX, anti-TNF, glucocorticoids) and RA severity/activity markers (RA disease duration, mean DAS, CRP, RF positivity, anti-CCP positivity). Multivariate linear regression was performed to determine the factors associated with LDL, HDL and TG levels. RESULTS: The REL SNP rs9309331 homozygous minor allele was associated with higher LDL levels. Caucasian race and increasing BMI were associated with lower HDL. Factors associated with higher TG were diabetes, Caucasian race and higher BMI. CONCLUSION: The REL SNP rs9309331 was associated with LDL levels in our study. This association is a possible explanation of the increased risk of RA patients for CV disease and requires further inquiry.
23987103 Cancer risk in immune-mediated inflammatory diseases (IMID). 2013 Aug 29 Inflammation and cancer have a profound yet ambiguous relationship. Inflammation - especially chronic inflammation - has protumorigenic effects, but inflammatory cells also mediate an immune response against the tumor and immunosuppression is known to increase the risk for certain tumors.This article reviews current literature on the role of inflammation in cancer and the cancer risk in immune-mediated inflammatory diseases (IMIDs). We discuss the effect on cancer risk of different drug classes used in the treatment of IMIDs treatment, including biologicals such as tumor necrosis factor (TNF) inhibitors.Overall cancer incidence and mortality risk are similar to the general population in inflammatory bowel disease (IBD), and slightly increased for rheumatoid arthritis and psoriasis, with risk profiles differing for different tumor types. Increased risk for non-melanoma skin cancer is associated with thiopurine treatment in IBD, with the combination of anti-TNF and methotrexate in rheumatoid arthritis and with PUVA, cyclosporine and anti-TNF treatment in psoriasis. Data on the safety of using biologic or immunosuppressant therapy in IMID patients with a history of cancer are scarce.This review provides clinicians with a solid background to help them in making decisions about treatment of immune-mediated diseases in patients with a tumor history.This article is related to another review article in Molecular Cancer: http://www.molecular-cancer.com/content/12/1/86.
23711352 Identification of multiple, oxygen-stable HIF1 alpha isoforms, and augmented expression of 2013 Sep OBJECTIVES: To identify and quantitate hypoxia inducible factor 1 alpha (HIF1 α) isoforms in circulating peripheral blood mononuclear cells (PBMCs), and to assess their effects on target gene expression in rheumatoid arthritis (RA) patients. METHODS: PBMCs from healthy controls and from RA patients were analysed ex-vivo for expression of HIF isoforms, and target genes were assessed by RT-PCR. RESULTS: Transcripts of multiple HIF1α isoforms exist in circulating PBMCs. Expression of all these isoforms is dramatically, and maximally, augmented by foreign surface recognition. However, HIF1α protein stabilisation requires additional cell activation with phorbol ester. No difference in the expression or regulation of the HIF1α isoforms was seen between patients with active RA and healthy controls. However, analysis of a panel of HIF1α target genes revealed increased basal expression of the adrenomedullin gene in RA PBMCs, with resulting loss of further induction upon cell activation. CONCLUSIONS: Even in normoxia PBMCs express stable HIF1α protein on cell activation. Whilst multiple HIF1α isoforms exist in PBMCs no differences in expression were seen in RA compared with healthy controls. RA causes constitutive adrenomedullin expression in PBMCs that is not explicable by altered HIF expression, or stabilisation. Adrenomedullin has a variety of potential biological roles in RA, including regulation of angiogenesis, and aberrant gene regulation may be relevant in RA pathogenesis.
22990668 Activation of liver X receptors suppresses inflammatory gene expressions and transcription 2013 Jan OBJECTIVES: Liver X receptors (LXR) are nuclear receptors that play important roles in lipid metabolism and transport. LXR also suppress inflammatory responses in macrophages through a unique mechanism of transrepression. This study was performed to investigate whether the synthetic LXR agonist GW3965 can modulate the inflammatory status of fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA) and to identify the mechanism for their effect. METHODS: RA FLS were treated with 0.1 and 1 μM of GW3965, a synthetic LXR agonist. The mRNA expressions of pro-inflammatory mediators were measured using quantitative real-time PCR. Apoptotic cell death of RA FLS was assessed using TUNEL assay and determination of caspase-3 activity by a colorimetric assay. The levels of transcriptional corepressors including NCoR and SMRT were determined using western blot analyses. RESULTS: Treatment of RA FLS with GW3965 induced dose-dependent reductions in mRNA expression of pro-inflammatory mediators (IL-1β, IL-6, MMP-9, CCL-2, CCL-7, and COX-2). However, treatment with GW3965 at the concentration selected for this study had no effect on apoptosis of RA FLS. Decreased productions of NCoR and SMRT by LPS stimulation was attenuated by GW3965 treatment. CONCLUSIONS: GW3965 treatment suppressed mRNA expressions of pro-inflammatory mediators from RA FLS and inhibited the clearance of transcriptional corepressors. These data suggest that LXR activation can be used as a therapeutic approach to reduce the synovial inflammation in RA.
24470178 Canadian estimates of health care utilization costs for rheumatoid arthritis patients with 2014 Sep OBJECTIVE: To provide Canadian estimates of health care utilization costs associated with rheumatoid arthritis (RA)-related and non-RA-related care within 4 treatment strategies and in different physical functioning categories. METHODS: In the Alberta Rheumatoid Arthritis Biologics Pharmacosurveillance Program, clinical data were linked with provincial health care administrative databases to estimate health care costs. A propensity score matching technique was used to evaluate annual costs across 4 treatment strategies: 1) remaining on disease-modifying antirheumatic drugs and not progressing to therapy with a biologic agent (n = 75), 2) progressing to biologic agents (n = 68), 3) initiation and stabilization on a first anti-tumor necrosis factor agent (n = 731), or 4) requiring a switch to another biologic agent (n = 212). Costs were examined across levels of function and by cost attribution category (directly related to RA or not). RESULTS: Of 1,222 patients, 1,086 had at least 3 months of administrative data. The mean annual total cost per patient was $5,531 (median $2,568), and $2,349 (median $0) was accounted for by hospitalizations, $1,716 (median $1,358) by physician visits, and $1,465 (median $949) by emergency room and other outpatient visits. Of these costs, 41% was directly related to RA itself or associated comorbidities. The importance of physical function as a determinant of health care utilization was evident, with the annual mean cost for those with low functional disability as measured by a Health Assessment Questionnaire (HAQ) score <0.5 was $4,157 compared to $14,225 for those with a HAQ score >2.0 indicating high disability. CONCLUSION: Health care costs for RA can be minimized by aiming for better disease control and maintaining physical function.
24449573 Structural changes and antibody enrichment in the lungs are early features of anti-citrull 2014 Jan OBJECTIVE: It has been suggested that immunologic events in the lungs may be involved in triggering immunity, in particular production of anti-citrullinated protein antibodies (ACPAs) during early phases of rheumatoid arthritis (RA). The aim of this study was to investigate the structural and immunologic features of the lungs in incident cases of early RA in relation to ACPA presence and smoking status. METHODS: High-resolution computed tomography (HRCT) was used to examine the lungs of 105 patients with early, untreated RA (70 with ACPA-positive RA and 35 with ACPA-negative RA) and 43 healthy individuals. Bronchoscopy with collection of bronchoalveolar lavage (BAL) fluid and mucosal bronchial biopsy specimens was performed in 23 RA patients. The presence of citrullinated proteins in the bronchial tissue was detected by immunohistochemical staining. ACPAs (detected with an anti-cyclic citrullinated peptide 2 test) and total Ig levels were determined in the sera and BAL fluid of RA patients. RESULTS: HRCT imaging revealed that 63% of ACPA-positive RA patients had parenchymal lung abnormalities, compared with only 37% of ACPA-negative RA patients and 30% of healthy controls (each P < 0.05). These significant differences remained after adjustment for smoking status. Airway changes detected by HRCT were more frequent in RA patients than in healthy controls (66% versus 42%; P < 0.05), but there was no difference between ACPA-positive and ACPA-negative RA patients. Immunohistochemical studies of the bronchial tissue showed increased staining for citrullinated proteins in ACPA-positive RA patients compared with ACPA-negative RA patients (P < 0.05). ACPA levels were relatively higher in the BAL fluid as compared with the sera of ACPA-positive RA patients, suggesting that there is local production of ACPAs in the lungs of these patients. CONCLUSION: The presence of ACPAs is associated with parenchymal lung abnormalities, site-specific citrullination, and antibody enrichment in the lungs early in the development of ACPA-positive RA.
24488413 Independent relationship of osteoprotegerin concentrations with endothelial activation and 2014 Mar OBJECTIVE: Osteoprotegerin (OPG) may contribute to the link between systemic inflammation and increased cardiovascular risk. We investigated the relationship of OPG concentrations with endothelial activation and carotid atherosclerosis in rheumatoid arthritis (RA). METHODS: OPG concentrations and those of endothelial activation molecules were measured by using ELISA in 34 patients who were treated with infliximab (IFX), both immediately before and after an IFX infusion. Carotid intima-media thickness (CIMT) and plaque were determined by ultrasound in 27 of the study participants. RESULTS: Median (interquartile range) OPG concentrations decreased from 4.8 pmol/l (2.8-6.5) to 4.4 pmol/l (2.9-6.1; p = 0.04) upon IFX infusion. Baseline OPG concentrations were inversely associated with those of total and low-density lipoprotein (LDL) cholesterol (partial R = -0.50, p = 0.004, and R = -0.48, p = 0.007, respectively). Prior to IFX administration, OPG concentrations were associated with those of intercellular adhesion molecule (ICAM)-1 (partial R = 0.34, p = 0.05), CIMT (partial R = 0.51 to 0.52, p < 0.009), and plaque (OR = 1.52, 95% CI 1.01-2.29 to OR = 1.61, 95% CI 1.03-2.51; p < 0.04), independent of conventional risk factors and C-reactive protein concentrations or disease activity. Except for the OPG concentrations-plaque association (p = 0.09), these relationships remained significant subsequent to IFX administration (p < 0.05). Reductions in OPG levels related to those in vascular cell adhesion molecule (VCAM)-1 concentrations (partial R = 0.35, p = 0.04) and had borderline significance (p = 0.09) with those in ICAM-1 (partial R = 0.29) concentrations. CONCLUSION: OPG concentrations are independently associated with endothelial activation and carotid atherosclerosis in RA. Reductions in OPG concentrations upon IFX administration are associated with decreased endothelial activation. OPG may be involved in increased cardiovascular disease risk and may improve its stratification in patients with RA.
25057856 B cell receptor signaling-based index as a biomarker for the loss of peripheral immune tol 2014 This study examines the loss of peripherally induced B cell immune tolerance in Rheumatoid arthritis (RA) and establishes a novel signaling-based measure of activation in a subset of autoreactive B cells--the Induced tolerance status index (ITSI). Naturally occurring naïve autoreactive B cells can escape the "classical" tolerogenic mechanisms of clonal deletion and receptor editing, but remain peripherally tolerized through B cell receptor (BCR) signaling inhibition (postdevelopmental "receptor tuning" or anergy). ITSI is a statistical index that numerically determines the level of homology between activation patterns of BCR signaling intermediaries in B cells that are either tolerized or activated by auto antigen exposure, and thus quantifies the level of peripheral immune tolerance. The index is based on the logistic regression analysis of phosphorylation levels in a panel of BCR signaling proteins. Our results demonstrate a new approach to identifying autoreactive B cells based on their BCR signaling features.
24470436 Effect of hydroxychloroquine on insulin sensitivity and lipid parameters in rheumatoid art 2014 Aug OBJECTIVE: Observational studies suggest that hydroxychloroquine (HCQ) may reduce the risk of developing diabetes mellitus in patients with rheumatoid arthritis (RA). We examined the effect of HCQ on insulin resistance in subjects without diabetes mellitus with stable RA. METHODS: Twenty-three RA subjects not currently using HCQ completed a 16-week, double-blind crossover study. Subjects were randomly allocated to receive HCQ (6.5 mg/kg/day) or placebo for the first 8 weeks, followed by crossover to the other arm for the final 8 weeks. Subjects underwent oral glucose tolerance testing and fasting lipid measurements at baseline, 8 weeks, and 16 weeks. The change ± SD from baseline in insulin sensitivity index (ISI), homeostatic model assessment for insulin resistance (HOMA-IR), and lipid parameters were compared between placebo and HCQ using linear regression. RESULTS: The mean patient age was 56 years, with 96% women, and the median body mass index was 26.0 kg/m2. After 8 weeks of HCQ, the mean ± SD ISI increase was 0.4 ± 2.9 compared with a small increase during placebo of 0.14 ± 3.1 (adjusted P = 0.785), and the mean ± SD HOMA-IR decrease was 0.3 ± 1.5 during HCQ versus a decrease of 0.42 ± 1.4 during placebo (adjusted P = 0.308). Small decreases in total cholesterol (12.7 mg/dl) and low-density lipoprotein (LDL) cholesterol (12.4 mg/dl) were observed during the HCQ treatment periods (both adjusted P < 0.05 compared to placebo). CONCLUSION: HCQ use for 8 weeks in patients without diabetes mellitus with stable RA produced no significant change in insulin resistance. We observed small and statistically significant improvements in total and LDL cholesterol during HCQ treatment.
24249648 Modified-release prednisone: in patients with rheumatoid arthritis. 2013 Dec Prednisone is a well-established treatment option in rheumatoid arthritis. Low-dose glucocorticoid therapy alleviates disease signs and symptoms, is better tolerated than high-dose therapy, and its addition to disease-modifying anti-rheumatic drugs (DMARDs) inhibits radiographic disease progression. A low-dose, modified-release (MR) formulation of prednisone, administered in the evening, was developed to counter the circadian rise in pro-inflammatory cytokine levels that contributes to disease activity. In a 12-week, randomized trial (CAPRA-2) in adult patients with rheumatoid arthritis who were receiving stable DMARD therapy, the addition of MR prednisone reduced disease signs and symptoms by ≥20 % according to the American College of Rheumatology criteria (in 48 % of patients vs. 29 % with placebo; p < 0.002 [primary endpoint]). In another 12-week trial (CAPRA-1), addition of evening MR prednisone to stable DMARD therapy reduced the mean duration of morning stiffness to a greater extent than addition of morning immediate-release (IR) prednisone (22.7 vs. 0.4 %; p = 0.045 [primary endpoint]). The improvement in morning stiffness with MR prednisone was maintained for 9-12 months during the open-label extension of CAPRA-1. These findings were supported by data from observational studies in various adult populations with rheumatoid arthritis. Treatment with evening MR prednisone for up to 12 months was generally well tolerated, with an overall similar tolerability profile compared with evening placebo or morning IR prednisone, and no new safety concerns. MR prednisone was estimated to be cost effective relative to IR prednisone in patients with rheumatoid arthritis in a UK pharmacoeconomic model.
23129416 A case-control study on the association between rheumatoid arthritis and bladder pain synd 2013 Sep AIM: While bladder pain syndrome/interstitial cystitis (BPS/IC) has been suggested by a number of studies to have autoimmune character, no population-based study to date has been conducted investigating its association with rheumatoid arthritis (RA). This study aimed to examine the association between IC/BPS and having previously been diagnosed with RA. METHODS: We conducted this study by using administrative claims data sourced from the Taiwan National Health Insurance Database. Our study included 9,269 cases with BPS/IC and 46,345 randomly selected controls. Conditional logistic regression was performed to calculate the odds ratio (OR) for the association between previously diagnosed RA and IC/BPS. RESULTS: RA was found among 202 (2.2%) cases and 504 (1.12%) controls. Conditional logistic regression analysis suggested that when compared with controls, the OR for prior RA among cases was 1.66 (95% CI = 1.47-1.87, P < 0.001) after adjusting for diabetes, hypertension, coronary heart disease, obesity, hyperlipidemia, chronic pelvic pain, irritable bowel syndrome, fibromyalgia, chronic fatigue syndrome, depression, panic disorder, migraine, sicca syndrome, allergy, endometriosis, asthma, overactive bladder, tobacco use disorder, and alcohol abuse. Additionally, BPS/IC was consistently and significantly associated with a previous diagnosis of RA regardless of prescription drug use; the OR for prior RA among groups prescribed ≤1 type of disease-modifying antirheumatic drug (DMARD), two types of DMARDs, and ≥3 types of DMARDs or TNF-alpha inhibitor when compared to controls were 1.49 (95% CI = 1.28-1.72), 1.91 (95% CI = 1.38-2.68), and 2.36 (95% CI = 1.77-3.17), respectively. CONCLUSIONS: There is an association between RA and BPS/IC after adjusting for socio-demographic characteristics and medical co-morbidities.