bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence of and predictive factors for sustained disease‐modifying antirheumatic drug–free remission in rheumatoid arthritis: Results from two large early arthritis cohorts
Authors: van der Woude Diane , Young Adam , Jayakumar Keeranur , Mertens Bart J. , Toes René E. M. , van der Heijde Désirée , Huizinga Tom W. J. , van der Helm‐van Mil Annette H. M. 
Published: July 2009

AbstractObjectiveRemission has become an attainable goal of rheumatoid arthritis (RA) treatment, especially since the advent of biologic antirheumatic therapy. Because little is known about patients who achieve disease remission with conventional treatment, we used 2 large independent inception cohorts to study the prevalence of and predictive factors for disease‐modifying antirheumatic drug (DMARD)–free sustained remission after treatment with conventional therapy.MethodsRemission of disease was assessed in 454 patients from the Leiden Early Arthritis Clinic (EAC) and in 895 patients from the British Early Rheumatoid Arthritis Study (ERAS) who fulfilled the American College of Rheumatology 1987 revised criteria for the classification of RA and were treated with conventional therapy. Sustained DMARD‐free remission was defined as fulfilling the following criteria for at least 1 year: 1) no current DMARD use, 2) no swollen joints, and 3) classification as DMARD‐free remission by the patient's rheumatologist. Predictive factors were identified by Cox regression analysis.ResultsSustained DMARD‐free remission was achieved by 68 of 454 patients (15.0%) in the Leiden EAC and by 84 of 895 patients (9.4%) in the ERAS. Six factors were associated with sustained DMARD‐free remission in both cohorts: acute onset, short symptom duration before inclusion, not smoking, little radiographic damage at baseline, absence of IgM rheumatoid factor (IgM‐RF), and absence of HLA shared epitope alleles. In the ERAS, low disease activity at baseline was also predictive of remission. Multivariate analyses revealed symptom duration and the absence of autoantibodies (anti–cyclic citrullinated peptide 2 and IgM‐RF) as independent predictors.ConclusionSustained DMARD‐free remission in RA patients treated with conventional therapy is not uncommon. Symptom duration at presentation and the absence of autoantibodies are associated with sustained DMARD‐free remission.
Dysfunctional proinflammatory high‐density lipoproteins confer increased risk of atherosclerosis in women with systemic lupus erythematosus
Authors: McMahon Maureen , Grossman Jennifer , Skaggs Brian , FitzGerald John , Sahakian Lori , Ragavendra Nagesh , Charles‐Schoeman Christina , Watson Karol , Wong Weng Kee , Volkmann Elizabeth , Chen Weiling , Gorn Alan , Karpouzas George , Weisman Michael , Wallace Daniel J. , Hahn Bevra H. 
Published: July 2009

AbstractObjectiveWomen with systemic lupus erythematosus (SLE) have an increased risk of atherosclerosis. Identification of at‐risk patients and the etiology underlying atherosclerosis in SLE remain elusive. The antioxidant capacity of normal high‐density lipoproteins (HDLs) is lost during inflammation, and these dysfunctional HDLs might predispose individuals to atherosclerosis. The aim of this study was to determine whether dysfunctional proinflammatory HDL (piHDL) is associated with subclinical atherosclerosis in SLE.MethodsCarotid artery ultrasound was performed in 276 women with SLE to identify carotid plaques and measure intima‐media thickness (IMT). The antioxidant function of HDL was measured as the change in oxidation of low‐density lipoprotein after the addition of HDL cholesterol. Two antiinflammatory HDL components, paraoxonase 1 and apolipoprotein A‐I, were also measured.ResultsAmong the SLE patients, 48.2% were determined to have piHDL on carotid ultrasound, while 86.7% of patients with plaque had piHDL compared with 40.7% of those without plaque (P < 0.001). Patients with piHDL also had a higher IMT (P < 0.001). After multivariate analysis, the only factors found to be significantly associated with plaque were the presence of piHDL (odds ratio [OR] 16.1, P < 0.001), older age (OR 1.2, P < 0.001), hypertension (OR 3.0, P = 0.04), dyslipidemia (OR 3.4, P = 0.04), and mixed racial background (OR 8.3, P = 0.04). Factors associated with IMT measurements in the highest quartile were the presence of piHDL (OR 2.5, P = 0.02), older age (OR 1.1, P < 0.001), a higher body mass index (OR 1.07, P = 0.04), a cumulative lifetime prednisone dose ≥20 gm (OR 2.9, P = 0.04), and African American race (OR 8.3, P = 0.001).ConclusionDysfunctional piHDL greatly increases the risk of developing subclinical atherosclerosis in SLE. The presence of piHDL was associated with an increased prevalence of carotid plaque and with a higher IMT. Therefore, determination of piHDL may help identify patients at risk for atherosclerosis.
Studies of cell‐mediated immune responses to influenza vaccination in systemic lupus erythematosus
Authors: Holvast Albert , van Assen Sander , de Haan Aalzen , Huckriede Anke , Benne Cornelis A. , Westra Johanna , Palache Abraham , Wilschut Jan , Kallenberg Cees G. M. , Bijl Marc 
Published: July 2009

AbstractObjectiveBoth antibody and cell‐mediated responses are involved in the defense against influenza. In patients with systemic lupus erythematosus (SLE), a decreased antibody response to subunit influenza vaccine has been demonstrated, but cell‐mediated responses have not yet been assessed. This study was therefore undertaken to assess cell‐mediated responses to influenza vaccination in patients with SLE.MethodsFifty‐four patients with SLE and 54 healthy control subjects received subunit influenza vaccine. Peripheral blood mononuclear cells and sera were obtained before and 1 month after vaccination. Cell‐mediated responses to A/H1N1 and A/H3N2 vaccines were evaluated using an interferon‐γ (IFNγ) enzyme‐linked immunospot assay and flow cytometry. Antibody responses were measured using a hemagglutination inhibition test.ResultsPrior to vaccination, patients with SLE had fewer IFNγ spot‐forming cells against A/H1N1 compared with control subjects and a lower frequency of IFNγ‐positive CD8+ T cells. After vaccination, the number of IFNγ spot‐forming cells increased in both patients and control subjects, although the number remained lower in patients. In addition, the frequencies of CD4+ T cells producing tumor necrosis factor and interleukin‐2 were lower in patients after vaccination compared with healthy control subjects. As expected for a subunit vaccine, vaccination did not induce a CD8+ T cell response. For A/H3N2‐specific responses, results were comparable. Diminished cell‐mediated responses to influenza vaccination were associated with the use of prednisone and/or azathioprine. The increase in A/H1N1‐specific and A/H3N2‐specific antibody titers after vaccination was lower in patients compared with control subjects.ConclusionIn addition to a decreased antibody response, cell‐mediated responses to influenza vaccination are diminished in patients with SLE, which may reflect the effects of the concomitant use of immunosuppressive drugs. This may render these patients more susceptible to (complicated) influenza infections.
Course of the modified Rodnan skin thickness score in systemic sclerosis clinical trials: Analysis of three large multicenter, double‐blind, randomized controlled trials
Authors: Amjadi Sogol , Maranian Paul , Furst Daniel E. , Clements Philip J. , Wong Weng Kee , Postlethwaite Arnold E. , Khanna Puja P. , Khanna Dinesh 
Published: July 2009

AbstractObjectiveTo assess the course of the modified Rodnan skin thickness score (MRSS) in 3 large, multicenter, double‐blind, randomized controlled trials (RCTs) of patients with diffuse cutaneous systemic sclerosis (dcSSc) with different baseline disease durations, as defined from the date of onset of the first dcSSc symptom (excluding Raynaud's phenomenon) or from the date of onset of the first dcSSc‐related symptom (including Raynaud's phenomenon).MethodsData from 3 RCTs examining high‐dose versus low‐dose D‐penicillamine (D‐Pen Trial), recombinant human relaxin versus placebo (Relaxin Trial), and oral bovine type I collagen versus placebo (Collagen Trial) treatment in patients with dcSSc were pooled and analyzed. Patients were divided into 5 groups according to their disease duration at baseline. The linear mixed model for correlated data was used to model the 2 predictors of MRSS: time in study (expressed in months after baseline) and baseline disease duration (expressed in months, calculated from the date of onset of the first symptom characteristic of dcSSc with and without Raynaud's phenomenon).ResultsAt study entry, the mean MRSS value was 21.0 in the D‐Pen Trial cohort, 27.3 in the Relaxin Trial cohort, and 26.1 in the Collagen Trial cohort. Time in study was a significant predictor of improvement in MRSS regardless of the disease duration at baseline (P < 0.0001). Patients with a disease duration of ≥24 months showed a greater rate of decline as compared with patients with a disease duration of <24 months (P < 0.05). Similar results were obtained when disease duration was reclassified by including the time of the first Raynaud's phenomenon symptom in the definition.ConclusionOur study confirms recent findings that in patients entered into these 3 RCTs, skin thickening did not follow the same trend in natural history as that seen in the dcSSc populations entered into early, open longitudinal studies previously reported. These findings have important implications for study design, in which “prevention of worsening” is the main objective.
Independent association of anti–β2‐glycoprotein I antibodies with macrovascular disease and mortality in scleroderma patients
Authors: Boin Francesco , Franchini Stefano , Colantuoni Elizabeth , Rosen Antony , Wigley Fredrick M. , Casciola‐Rosen Livia 
Published: July 2009

AbstractObjectiveSystemic sclerosis (SSc; scleroderma) is characterized by a unique widespread vascular involvement that can lead to severe digital ischemia, pulmonary arterial hypertension (PAH), or other organ dysfunction. Microthrombotic events and procoagulation factors such as anti–β2‐glycoprotein I (anti‐β2GPI) or anticardiolipin antibodies (aCL) may be implicated in the development of these manifestations. This study was undertaken to investigate whether anti‐β2GPI and aCL are correlated with macrovascular disease, including ischemic digital loss and PAH, in SSc patients.MethodsSeventy‐five SSc patients with a history of ischemic digital loss and 75 matched SSc controls were evaluated. Anticentromere antibodies (ACAs), anti‐β2GPI, and aCL were measured, and clinical associations were determined using conditional and simple logistic regression models.ResultsPositivity for anti‐β2GPI was significantly more frequent in SSc patients with digital loss than in patients without digital loss (P = 0.017), with the IgA isotype of anti‐β2GPI showing the strongest association (odds ratio [OR] 4.0). There was no significant difference in aCL frequency between patients with digital loss and control patients. After adjustment for demographic characteristics, disease type, smoking, and ACA, anti‐β2GPI positivity was significantly associated with active digital ischemia (OR 9.4), echocardiographically evident PAH (OR 4.8), and mortality (OR 2.9). ACA positivity was associated with history of digital loss (OR 3.28), but not with PAH or mortality. History of digital loss was strongly associated with increased mortality (OR 12.5).ConclusionAnti‐β2GPI is significantly associated with macrovascular disease in SSc and independently predicts mortality. It is unclear whether it has a pathogenetic role or simply reveals the presence of underlying endothelial injury. The use of anti‐β2GPI as a biomarker of vascular disease in SSc should be further explored.
Methotrexate catabolism to 7‐hydroxymethotrexate in rheumatoid arthritis alters drug efficacy and retention and is reduced by folic acid supplementation
Authors: Baggott Joseph E. , Morgan Sarah L. 
Published: July 2009

AbstractObjectiveTo assess the catabolism of methotrexate (MTX) to 7‐hydroxy‐MTX (7‐OH‐MTX) in patients with rheumatoid arthritis as well as the effect of folic acid and folinic acid on this catabolism.MethodsUrinary excretion of MTX and its catabolite, 7‐OH‐MTX, was measured in 2 24‐hour urine specimens collected after MTX therapy. Urine samples were collected from patients after the sixth and seventh weekly doses of MTX. MTX and 7‐OH‐MTX concentrations were determined by high‐performance liquid chromatography mass spectrometry. Swelling and pain/tenderness indices were used to measure symptoms before and at 6 and 7 weeks of therapy. Patients received either folic acid or folinic acid supplements (1 mg/day) from week 6 to week 7.ResultsFolic acid inhibited aldehyde oxidase (AO), the enzyme that produces 7‐OH‐MTX, but folinic acid did not. Excretion of 7‐OH‐MTX (determined as a percentage of the dose of MTX or as mg 7‐OH‐MTX/gm creatinine) was not normally distributed (n = 39). Patients with marked improvement in swelling and pain/tenderness indices had a lower mean 7‐OH‐MTX excretion level (P < 0.05). Patients who received folic acid supplements had decreased 7‐OH‐MTX excretion (P = 0.03). Relatively high 7‐OH‐MTX excretion was correlated with relatively high MTX excretion and with relatively low MTX retention in vivo (P < 0.05) (n = 35).ConclusionOur findings of a non‐normal distribution of 7‐OH‐MTX excretion suggest that there are at least 2 phenotypes for this catabolism. Decreased 7‐OH‐MTX formation suggests folic acid inhibition of AO and a better clinical response, while increased 7‐OH‐MTX formation may interfere with MTX polyglutamylation and binding to enzymes and, therefore, may increase MTX excretion and decrease MTX retention and efficacy in vivo.
Physical activity in women with arthritis: Examining perceived barriers and self‐regulatory efficacy to cope
Authors: Gyurcsik Nancy C. , Brawley Lawrence R. , Spink Kevin S. , Brittain Danielle R. , Fuller Daniel L. , Chad Karen 
Published: July 2009

AbstractObjectiveTo examine whether the theory‐based social cognitions of perceived barrier frequency, barrier limitation, and self‐regulatory efficacy to cope were predictors of planned physical activity among adult women with arthritis. A secondary purpose was to identify and provide a phenomenologic description of the relevant barriers and coping strategies reported by study participants.MethodsEighty adult women (mean ± SD age 49.09 ± 12.89 years) with self‐reported doctor‐diagnosed arthritis participated in this observational study. Participants completed online survey measures of barriers to physical activity and, for each barrier, reported the frequency of occurrence and the extent of limitation. Measures of coping strategies for each barrier, efficacy to cope, and physical activity were also obtained.ResultsA multiple hierarchical regression analysis resulted in a model that significantly predicted physical activity (F[9,70] = 6.80, P < 0.01, adjusted R2 = 0.40). Barrier limitation (standardized β = −0.56) and efficacy (standardized β = 0.20) were significant independent predictors. Phenomenologic findings indicated that arthritis‐specific personal barriers (e.g., pain and fatigue due to arthritis) and arthritis‐specific coping strategies (e.g., activity modification) were more commonly reported than generic barriers and coping strategies.ConclusionSelf‐regulatory efficacy to cope and relevant perceived physical activity barriers, which were primarily arthritis‐specific and moderately or more limiting to planned physical activity, were important social cognitive predictors of physical activity, a key nonpharmacologic arthritis treatment, among women with arthritis. Future research direction should examine potential moderators of the relationship between these predictors and physical activity, such as pain acceptance.
Association of STAT4 and BLK, but not BANK1 or IRF5, with primary antiphospholipid syndrome
Authors: Yin Hong , Borghi Maria Orietta , Delgado‐Vega Angélica M. , Tincani Angela , Meroni Pier‐Luigi , Alarcón‐Riquelme Marta E. 
Published: July 2009

AbstractObjectivePrimary antiphospholipid syndrome (APS) is formally classified by the presence of antiphospholipid antibodies, recurrent thrombosis, and/or pregnancy morbidity in the absence of any underlying full‐blown systemic autoimmune disease. However, systemic manifestations in patients with primary APS have been recently reported, as has the presence of serologic markers in common with systemic lupus erythematosus (SLE). In spite of similarities between the 2 diseases, only a minority of cases of primary APS evolve into full‐blown SLE, even after a long followup period. The aim of this study was to investigate whether the analysis of SLE susceptibility genes may provide at least a partial explanation for such a discrepancy.MethodsOne hundred thirty‐three patients with primary APS classified according to the Sydney criteria and 468 healthy control subjects from the same geographic area were recruited. We genotyped 3 single‐nucleotide polymorphisms (SNPs) in IRF5 (rs2004640, rs2070197, and rs10954213), 4 SNPs in STAT4 (rs1467199, rs3821236, rs3024866, and rs7574865), 2 SNPs in BANK1 (rs10516487 and rs3733197), and 1 SNP in BLK (rs2736340).ResultsSTAT4 and BLK displayed a strong genetic association with primary APS (for rs7574865, odds ratio [OR] 2.19, P = 5.17 × 10−7; for rs2736340, OR 2.06, P = 1.78 × 10−6), while a weak association with IRF5 and no association with BANK1 were observed.ConclusionThe presence of a strong genetic association with only a few SLE susceptibility genes and the absence of a more complex gene association may contribute to the lack of cases of full‐blown SLE developing in patients with primary APS, in spite of the clinical and serologic similarities between SLE and primary APS.
Ultraviolet radiation intensity predicts the relative distribution of dermatomyositis and anti–Mi‐2 autoantibodies in women
Authors: Love Lori A. , Weinberg Clarice R. , McConnaughey D. Robert , Oddis Chester V. , Medsger Thomas A. , Reveille John D. , Arnett Frank C. , Targoff Ira N. , Miller Frederick W. 
Published: July 2009

AbstractObjectiveBecause studies suggest that ultraviolet (UV) radiation modulates the myositis phenotype and Mi‐2 autoantigen expression, we conducted a retrospective investigation to determine whether UV radiation may influence the relative prevalence of dermatomyositis and anti–Mi‐2 autoantibodies in the US.MethodsWe assessed the relationship between surface UV radiation intensity in the state of residence at the time of onset with the relative prevalence of dermatomyositis and myositis autoantibodies in 380 patients with myositis from referral centers in the US. Myositis autoantibodies were detected by validated immunoprecipitation assays. Surface UV radiation intensity was estimated from UV Index data collected by the US National Weather Service.ResultsUV radiation intensity was associated with the relative proportion of patients with dermatomyositis (odds ratio [OR] 2.3, 95% confidence interval [95% CI] 0.9–5.8) and with the proportion of patients expressing anti–Mi‐2 autoantibodies (OR 6.0, 95% CI 1.1–34.1). Modeling of these data showed that these associations were confined to women (OR 3.8, 95% CI 1.3–11.0 and OR 17.3, 95% CI 1.8–162.4, respectively) and suggests that sex influences the effects of UV radiation on autoimmune disorders. Significant associations were not observed in men, nor were UV radiation levels related to the presence of antisynthetase or anti–signal recognition particle autoantibodies.ConclusionThis first study of the distribution of myositis phenotypes and UV radiation exposure in the US showed that UV radiation may modulate the clinical and immunologic expression of autoimmune disease in women. Further investigation of the mechanisms by which these effects are produced may provide insights into pathogenesis and suggest therapeutic or preventative strategies.
Abrogation of antibody‐induced arthritis in mice by a self‐activating viridin prodrug and association with impaired neutrophil and endothelial cell function
Authors: Stangenberg Lars , Ellson Chris , Cortez‐Retamozo Virna , Ortiz‐Lopez Adriana , Yuan Hushan , Blois Joseph , Smith Ralph A. , Yaffe Michael B. , Weissleder Ralph , Benoist Christophe , Mathis Diane , Josephson Lee , Mahmood Umar 
Published: July 2009

AbstractObjectiveTo test a novel self‐activating viridin (SAV) prodrug that slowly releases wortmannin, a potent phosphoinositide 3‐kinase inhibitor, in a model of antibody‐mediated inflammatory arthritis.MethodsThe SAV prodrug was administered to K/BxN mice or to C57BL/6 (B6) mice that had been injected with K/BxN serum. Ankle thickness was measured, and histologic changes were scored after a 10‐day disease course (serum‐transfer arthritis). Protease activity was measured by a near‐infrared imaging approach using a cleavable cathepsin–selective probe. Further near‐infrared imaging techniques were used to analyze early changes in vascular permeability after serum injection, as well as neutrophil–endothelial cell interactions. Neutrophil functions were assessed using an oxidative burst assay as well as a degranulation assay.ResultsSAV prevented ankle swelling in mice with serum‐transfer arthritis in a dose‐dependent manner. It also markedly reduced the extent of other features of arthritis, such as protease activity and histology scores for inflammation and joint erosion. Moreover, SAV was an effective therapeutic agent. The underlying mechanisms for the antiinflammatory activity were manifold. Endothelial permeability after serum injection was reduced, as was firm neutrophil attachment to endothelial cells. Endothelial cell activation by tumor necrosis factor α was impeded by SAV, as measured by the expression of vascular cell adhesion molecule. Crucial neutrophil functions, such as generation of reactive oxygen species and degranulation of protease‐laden vesicles, were decreased by SAV administration.ConclusionA novel SAV prodrug proved strongly antiinflammatory in a murine model of antibody‐induced inflammatory arthritis. Its activity could be attributed, at least in part, to the inhibition of neutrophil and endothelial cell functions.