Objective. To study 5 type I interferon (IFN)-inducible genes (LY6E, OAS1, OASL, MX1, and ISG15) in patients with systemic lupus erythematosus (SLE) and to correlate expression levels with disease activity and/or clinical manifestations.Methods. Peripheral blood cells were obtained from 48 SLE patients, 48 normal controls, and 22 rheumatic disease controls, and total RNA was extracted and reverse transcribed into complementary DNA. Gene expression levels were measured by realtime polymerase chain reaction, standardized to a housekeeping gene, and summed to an IFN score. Disease activity was determined by the Safety of Estrogens in Lupus Erythematosus: National AssessmentSystemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) composite.Results. Each gene was highly expressed in SLE patients compared with normal controls (P < 0.0003) or disease controls (P < 0.0008 except for MX1). IFN scores were positively associated with the SELENA-SLEDAI instrument score (P ؍ 0.001), the SELENA-SLEDAI flare score (P ؍ 0.03), and the physician's global assessment score (P ؍ 0.005). Compared with patients without nephritis, lupus nephritis patients had higher IFN scores (overall P < 0.0001), especially during active renal disease. IFN scores were weakly associated with neurologic manifestations. Elevated IFN scores were positively associated with the current presence of anti-double-stranded DNA (anti-dsDNA) antibodies (P ؍ 0.007) or hypocomplementemia (P ؍ 0.007). LY6E expression levels distinguished active from inactive lupus nephritis (P ؍ 0.02) and were positively associated with proteinuria (P ؍ 0.009).Conclusion. The 5 IFN-inducible genes were highly expressed in SLE patients, and increased levels were correlated with disease activity defined by several methods. IFN scores, or LY6E levels, were elevated in lupus nephritis patients, especially during active renal disease, and in patients with anti-dsDNA antibody positivity and hypocomplementemia. IFN scores, or LY6E levels, may be useful as a biomarker for lupus nephritis therapy.Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by immune dysregulation resulting in the production of antinuclear and other autoantibodies, generation of circulating immune complexes, and activation of the complement system. The disease course of SLE is heterogeneous, affecting different individuals with a wide range of manifestations. Unpredictable flares and improvements may be observed. There is no specific single diagnostic test for SLE, and therapy is typically initiated after signs of
Objectives Reverse cholesterol transport (RCT) is a major antiatherogenic function of high density lipoprotein (HDL). In the current work, the authors evaluated whether the RCT capacity of HDL from rheumatoid arthritis (RA) patients is impaired when compared to healthy controls. Methods HDL was isolated from 40 patients with RA and 40 age and sex matched healthy controls. Assays of cholesterol efflux, HDL’s antioxidant function and paraoxanase-1 (PON-1) activity were performed as described previously. Plasma myeloperoxidase (MPO) activity was assessed by a commercially available assay. Results Mean cholesterol efflux capacity of HDL was not significantly different between RA patients (40.2%±11.1%) and controls (39.5%±8.9%); p=0.75. However, HDL from RA patients with high disease activity measured by a disease activity score using 28 joint count (DAS28>5.1), had significantly decreased ability to promote cholesterol efflux compared to HDL from patients with very low disease activity/clinical remission (DAS28<2.6). Significant correlations were noted between cholesterol efflux and the DAS28 (r=−0.39, p=0.01) and erythrocyte sedimentation rate, (r=−0.41, p=0.0009). Higher plasma MPO activity was associated with worse HDL function (r=0.41/p=0.009 (antioxidant capacity); r=0.35, p=0.03 (efflux)). HDL’s ability to promote cholesterol efflux was modestly but significantly correlated with its antioxidant function (r=−0.34, p=0.03). Conclusions The cholesterol efflux capacity of HDL is impaired in RA patients with high disease activity and is correlated with systemic inflammation and HDL’s antioxidant capacity. Attenuation of HDL function, independent of HDL cholesterol levels, may suggest a mechanism by which active RA contributes to increased cardiovascular (CV) risk.
Objective-Rheumatoid arthritis (RA) is a chronic, disabling disease that can greatly compromise health related quality of life (HRQOL). The aim of this study was to assess the impact of a 6-week twice/week Iyengar yoga (IY) program on HRQOL of young adults with RA compared to a usual-care waitlist control group.Method-The program was designed to improve the primary outcome of HRQOL including pain, as well as disability and psychological functioning in patients. Assessments were collected pre, post, and at 2-months following treatment. Weekly ratings of anxiety, depression, pain and sleep were also recorded. A total of 26 participants completed the intervention (yoga = 11; usual care waitlist = 15). All participants were female (mean age =28 years).Results-Overall attrition was low at 15%. On average, women in the yoga group attended 96% of the yoga classes. No adverse events were reported. Relative to the usual-care waitlist, women assigned to the yoga program showed significantly greater improvement on standardized measures of HRQOL, pain disability, general health, mood, fatigue, acceptance of chronic pain and selfefficacy regarding pain at post treatment. Almost half of the yoga group reported clinically meaningful symptom improvement. Analysis of the uncontrolled effects and maintenance of treatment effects showed improvements in HRQOL general health, pain disability and weekly ratings of pain, anxiety and depression that maintained at follow-up. Conclusion-The findings suggest a brief IY intervention is a feasible and safe adjunctive treatment for young people with RA, leading to health related quality of life (HRQOL), pain disability, fatigue, and mood benefits. Moreover, improvements in quality of life, pain disability and mood persisted at the 2-month follow-up. KeywordsYoga; arthritis; young adults Rheumatoid arthritis (RA) is a chronic autoimmune disorder that can impact joint function and health-related quality-of-life (HRQOL), especially when arthritis develops early in a person's life [1,2]. Health care use, depression and pain are high amongst adolescents and Correspondence: Subhadra Evans, PhD, Pediatric Pain Program, Department of Pediatrics, David Geffen School of Medicine at UCLA, MDCC 22-464, 10833 Le Conte Ave 90024, United suevans@mednet.ucla.edu.. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Despite the need for physical and psychological treatments aimed at young people with RA, traditional approaches remain limited [4]. A multi-pronged treatment strategy is recommended, including rehabilitation efforts that promote a range of physical ...
Objective An increased frequency of atherosclerosis (ATH) in systemic lupus erythematosus (SLE) is well-documented but not fully explained by the presence of traditional cardiac risk factors. Several nontraditional biomarkers, including proinflammatory high-density lipoprotein (piHDL) and leptin, have been individually associated with subclinical ATH in SLE. The aim of this study was to examine whether these and other biomarkers can be combined into a risk profile, the Predictors of Risk for Elevated Flares, Damage Progression, and Increased Cardiovascular Disease in Patients with SLE (PREDICTS), that could be used to better predict future progression of ATH. Methods In total, 210 patients with SLE and 100 age-matched healthy control subjects (all women) participated in this prospective cohort study. The longitudinal presence of carotid plaque and intima-media thickness (IMT) were measured at baseline and followup (mean ± SD 29.6 ± 9.7 months). Results At followup, carotid plaque was present in 29% of SLE patients. Factors significantly associated with plaque, determined using Salford Predictive Modeling and multivariate analysis, included age ≥48 years (odds ratio [OR] 4.1, P = 0.002), high piHDL function (OR 9.1, P < 0.001), leptin levels ≥34 ng/dl (OR 7.3, P = 0.001), plasma soluble TWEAK levels ≥373 pg/ml (OR 28.8, P = 0.004), and history of diabetes (OR 61.8, P < 0.001). Homocysteine levels ≥12 μmoles/liter were also a predictor. However, no single variable demonstrated an ideal combination of good negative predictive values (NPVs), positive predictive values (PPVs), sensitivity, and specificity. A high-risk PREDICTS profile was defined as ≥3 positive biomarkers or ≥1 positive biomarker plus a history of diabetes; for high-risk SLE patients, the PPV was 64%, NPV was 94%, sensitivity was 89%, and specificity was 79%. In multivariate analysis, SLE patients with the high-risk profile had 28-fold increased odds for the longitudinal presence of plaque (P < 0.001) and increased progression of IMT (P < 0.001). Conclusion A high-risk PREDICTS score confers 28-fold increased odds of the presence of any current, progressive, or acquired carotid plaque, both in patients with SLE and in control subjects, and is significantly associated with higher rates of IMT progression.
Objective To assess whether ultrasonography (US) is reliable for the evaluation of inflammatory and structural abnormalities in patients with knee osteoarthritis (OA). Methods Thirteen patients with early knee OA were examined by 11 experienced sonographers during 2 days. Dichotomous and semiquantitative scoring was performed on synovitis characteristics in various aspects of the knee joint. Semiquantitative scoring was done of osteophytes at the medial and lateral femorotibial joint space or cartilage damage of the trochlea and on medial meniscal damage bilaterally. Intra-and interobserver reliability were computed by use of unweighted and weighted κ coefficients. Results Intra-and interobserver reliability scores were moderate to good for synovitis (mean κ 0.67 and 0.52, respectively) as well as moderate to good for the global synovitis (0.70 and 0.50, respectively). Mean intra-and interobserver reliability κ for cartilage damage, medial meniscal damage and osteophytes ranged from fair to good (0.55 and 0.34, 0.75 and 0.56, 0.73 and 0.60, respectively). Conclusions Using a standardised protocol, dichotomous and semiquantitative US scoring of pathological changes in knee OA can be reliable.
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