Low level of physical activity in women with rheumatoid arthritis is associated with cardiovascular risk factors but not with body fat mass - a cross sectional study

<p>Abstract</p> <p>Background</p> <p>As many patients with rheumatoid arthritis (RA) have increased fat mass (FM) and increased frequency of cardiovascular diseases we evaluated if total physical activity (MET-hours) had impact on body composition and cardiovascular risk factors in women with RA.</p> <p>Methods</p> <p>Sixty-one out-ward RA women, 60.8 (57.3-64.4) years, answered a self-administered questionnaire, to estimate total daily physical activity during the previous year. Physical activity level was given as metabolic equivalents (MET) × h/day. Diet content was assessed by a food frequency questionnaire and body composition by whole-body dual-energy X-ray absorptiometry. Blood lipids and antibodies against phosphorylcholine (anti-PC) were determined.</p> <p>Results</p> <p>Forty-one percent of the women had BMI > 25, 6% were centrally obese and 80% had FM% > 30%. The median (IQR) total physical activity was 40.0 (37.4-47.7), i.e. the same activity level as healthy Swedish women in the same age. Total physical activity did not significantly correlate with disease activity, BMI or FM%. Disease activity, BMI and FM% did not differ between those in the lowest quartile of total physical activity and those in the highest quartile. However, the women in the lowest quartile of physical activity had lower HDL (p = 0.05), Apo A1 (p = 0.005) and atheroprotective natural anti-PC (p = 0.016) and higher levels of insulin (p = 0.05) and higher frequency of insulin resistance than those in the highest quartile. Women in the lowest quartile consumed larger quantities of saturated fatty acids than those in the highest quartile (p = 0.042), which was associated with high oxidized low-density lipoprotein (oxLDL).</p> <p>Conclusion</p> <p>This cross sectional study demonstrated that RA women with fairly low disease activity, good functional capacity, high FM and high frequency of central obesity had the same total physical activity level as healthy Swedish women in the same age. The amount of total physical activity was not associated with functional capacity or body composition. However, low total physical activity was associated with dyslipidemia, insulin resistance, low levels of atheroprotective anti-PC and consumption of saturated fatty acids, which is of interest in the context of increased frequency of cardiovascular disease in RA.</p

Potential natural immunization against atherosclerosis in hibernating bears

Brown bears (Ursus arctos) hibernate for 5-6 months during winter, but despite kidney insufficiency, dyslipidemia and inactivity they do not seem to develop atherosclerosis or cardiovascular disease (CVD). IgM antibodies against phosphorylcholine (anti-PC) and malondialdehyde (anti-MDA) are associated with less atherosclerosis, CVD and mortality in uremia in humans and have anti-inflammatory and other potentially protective properties. PC but not MDA is exposed on different types of microorganisms. We determine anti-PC and anti-MDA in brown bears in summer and winter. Paired serum samples from 12 free ranging Swedish brown bears were collected during hibernation in winter and during active state in summer and analyzed for IgM, IgG, IgG1/2 and IgA anti-PC and anti-MDA by enzyme linked immunosorbent assay (ELISA). When determined as arbitrary units (median set at 100 for summer samples), significantly raised levels were observed in winter for anti-PC subclasses and isotypes, and for IgA anti-PC the difference was striking; 100 IQR (85.9-107.9) vs 782.3, IQR (422.8-1586.0; p<0.001). In contrast, subclasses and isotypes of anti-MDA were significantly lower in winter except IgA anti-MDA, which was not detectable. Anti-PCs are significantly raised during hibernation in brown bears; especially IgA anti-PC was strikingly high. In contrast, anti-MDA titers was decreased during hibernation. Our observation may represent natural immunization with microorganisms during a vulnerable period and could have therapeutic implications for prevention of atherosclerosis

Antibodies of IgM subclass to phosphorylcholine and oxidized LDL are protective factors for atherosclerosis in patients with hypertension

Objective: To determine the importance of antibodies against phosphorylcholine (PC) and oxidized low density lipoprotein (OxLDL) for development of atherosclerosis. Methods and results: Two hundred and twenty six individuals with established hypertension (diastolic pressure > 95 mmHg) were from European Lacidipine Study on Atherosclerosis. Antibodies of IgG and IgM subclass were tested by ELISA against PC (aPC), cupper-oxidized (ox)- or malondialdehyde (MDA)-modified LDL. High-sensitivity C-reactive protein was measured by nephelometry. As a surrogate measure of atherosclerosis, we used the mean of the maximum intima-media thicknesses (IMT) in the far walls of common carotids and bifurcations was determined by ultrasonography at the time of enrolment, and 4 years following enrolment. aPC could be competed out by PC and OxLDL, while cardiolipin (CL) and beta 2-glycoprotein I (beta 2GPI) were less effective and phosphatidylserine (PS) not at all. Increases in IMT at follow-up were less common in subjects which at the time of enrolment had high IgM aPC (both 75th and 90th; odds ratios: 0.46; Cl: 0.25-0.85; 0.36; Cl: 0.15-0.87) and high IgM aOxLDL and aMDA-LDL (90th; odds ratios 0.27; p = 0.01; Cl: 0.11-0.69 and 0.27; p = 0.01; Cl: 0.11-0.69). CRP was unrelated to IMT-changes. The relationship between IgM aPC, aOxLDL and aMDA-LDL and changes in IMT was independent of age, treatment with atenolol or lacidipine, smoking and lipids. Women had higher levels of IgM antibodies tested (p < 0.05). Conclusions: High levels of IgM-antibodies against PC and OxLDL predict a favourable outcome in the development of carotid atherosclerosis in hypertensive subjects. Whether these antibodies could be used therapeutically deserves further study. (c) 2005 Elsevier Ireland Ltd. All rights reserved

An elevated polyclonal free light chain level reflects a strong interferon signature in patients with systemic autoimmune diseases

The work described has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement No. 115565, the resources for which are composed of a financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and the European Federation of Pharmaceutical Industries and Associations (EFPIA) companies'in-kind contribution. We thank all the members of PRECISESADS Consortium and INSERM U1227 for their effort in the sample recruitment, distribution and assessment of the samples used in this study. We are grateful to Dr Wesley H Brooks (Tampa, USA) for editorial assistance and to Valerie Le Troadec for secretarial assistance.High amount of polyclonal free light chains (FLC) are reported in systemic autoimmune diseases (SAD) and we took advantage of the PRECISESADS study to better characterize them. Serum FLC levels were explored in 1979 patients with SAD (RA, SLE, SjS, Scl, APS, UCTD, MCTD) and 614 healthy controls. Information regarding clinical parameters, disease activity, medications, autoantibodies (Ab) and the interferon α and/or γ scores were recorded. Among SAD patients, 28.4% had raised total FLC (from 12% in RA to 30% in SLE and APS) with a normal kappa/ lambda ratio. Total FLC levels were significantly higher in SAD with inflammation, active disease in SLE and SjS, and an impaired pulmonary functional capacity in SSc, while independent from kidney impairment, infection, cancer and treatment. Total FLC concentrations were positively correlated among the 10/17 (58.8%) autoantibodies (Ab) tested with anti-RNA binding protein Ab (SSB, SSA-52/60 kDa, Sm, U1-RNP), anti-dsDNA/nucleosome Ab, rheumatoid factor and negatively correlated with complement fractions C3/C4. Finally, examination of interferon (IFN) expression as a potential driver of FLC overexpression was tested showing an elevated level of total FLC among patients with a high IFNα and IFNγ Kirou's score, a strong IFN modular score, and the detection in the sera of B-cell IFN dependent factors, such as TNF-R1/TNFRSF1A and CXCL10/IP10. In conclusion, an elevated level of FLC, in association with a strong IFN signature, defines a subgroup of SAD patients, including those without renal affectation, characterized by increased disease activity, autoreactivity, and complement reduction.Innovative Medicines Initiative Joint Undertaking 115565European Commission FP7/2007-2013European Federation of Pharmaceutical Industries and Associations (EFPIA)Institut National de la Sante et de la Recherche Medicale (Inserm)European Commission U122

Antibodies Against Phosphorylcholine Among 60-Year-Olds : Clinical Role and Simulated Interactions

AimsAntibodies against phosphorylcholine (anti-PC) are implicated as protection markers in atherosclerosis, cardiovascular disease (CVD), and other chronic inflammatory conditions. Mostly, these studies have been focused on IgM. In this study, we determined IgG, IgG1, and IgG2 anti-PC among 60-year-olds. MethodsBased on a 7-year follow-up of 60-year-olds (2,039 men and 2,193 women) from Stockholm County, we performed a nested case-control study of 209 incident CVD cases with 620 age- and sex-matched controls. Anti-PC was determined using ELISA. We predicted the binding affinity of PC with our fully human, in-house-produced IgG1 anti-PC clones (i.e., A01, D05, and E01) using the molecular docking and molecular dynamics simulation approach, to retrieve information regarding binding properties to PC. ResultsAfter adjustment for confounders, IgG and IgG2 anti-PC showed some significant associations, but IgG1 anti-PC was much stronger as a protection marker. IgG1 anti-PC was associated with an increased risk of CVD below 33rd, 25th, and 10th percentile and of stroke below 33rd and 25th, and of myocardial infarction (MI) below 10th percentile. Among men, a strong association with stroke was determined below the 33rd percentile [HR 9.20, CI (2.22-38.12); p = 0.0022]. D05 clone has higher binding affinity followed by E01 and A01 using molecular docking and further have been confirmed during the course of 100 ns simulation. The stability of the D05 clone with PC was substantially higher. ConclusionIgG1 anti-PC was a stronger protection marker than IgG anti-PC and IgG2 anti-PC and also separately for men. The molecular modeling approach helps in identifying the intrinsic properties of anti-PC clones and atomistic interactions with PC

Antiphospholipid autoantibody detection is important in all patients with systemic autoimmune diseases

International audienceAntiphospholipid (aPL) autoantibodies are uncommon in systemic autoimmune diseases (SADs). However, the European PRECISESADS study provides the opportunity to better characterize this rare association. The study was composed of 1818 patients with SADs including 453 with systemic lupus erythematosus (SLE), 359 with rheumatoid arthritis (RA), 385 with systemic sclerosis (SSc), 367 with Sjögren's syndrome (SjS), 94 with mixed connective tissue disease (MCTD), and 160 with undifferentiated connective tissue disease (UCTD). Assays used for aPL determination include the lupus anticoagulant (LAC) analysis using the dilute Russell's viper venom time (dRVVT) assay plus anti-cardiolipin (aCL) and anti-aβ2GPI autoantibodies of IgG and IgM isotype. Information regarding clinical and biological characteristics of SAD patients was available. Among SAD patients, the prevalence of aPL differs significantly between two groups: SLE (57.6%) and non-SLE SADs (13.7%, p < 10-4). Next, association between aPL plus thrombosis and miscarriage were observed in both SLE and non-SLE patients. Thrombosis was best predicted in SLE patients by dRVVT (OR = 6.1; IC95:3.5-10.3) and miscarriage by aCL±β2GPI IgG (OR = 2.5; IC95:1.2-5.2); while in non-SLE SADs the best predictors were aCL±β2GPI IgG for thrombosis (OR = 6.6; IC95:2.4-18.4) and aCL±β2GPI IgM for miscarriage (OR = 2.9; IC95:1.2-6.8). In the case of multiple positivity of aPL, the risk for thrombosis and miscarriage was increased. Central nervous system involvement characterized the SLE patients, in contrast to pulmonary and skin fibrosis, valve lesions, hypertension, elevated creatinemia, C4 fraction reduction, platelet reduction and inflammation that characterized the non-SLE SAD patients. Anti-PL determination remains important in SADs patients and should not be restricted to only SLE patients

Low levels of IgM antibodies against phosphorylcholine-A potential risk marker for ischemic stroke in men

Background: Natural antibodies specific for phosphorylcholine (anti-PC) have been implicated as protective factors in atherosclerosis. We herein determined the relationship between IgM anti-PC and incidence of cardiovascular disease (CVD). Methods: We studied 349 incident cases (200 men) of first events of CVD (coronary heart disease (CHD; n = 203 or ischemic stroke; n = 146) and 693 age- and sex-matched controls identified through 12 years of follow-up (1991-2003) of subjects from the cardiovascular cohort within the Malmo Diet and Cancer Study. Relative risks (RR) of CVD with 95% confidence intervals (CI) of incident CVD with adjustments for age, smoking, total cholesterol and blood pressure were determined. Anti-PC-levels were measured using ELISA (Athera CVDefine (TM)). Results: As determined using Athera CVDefine (TM), significant associations were attained with values of anti-PC below 17 U/ml (corresponding to the lowest 9th percentile), which remained after taking confounders into account (RR: 1.79, 95% CI: 1.09-2.94, p=0.021). If men were studied separately, significance was evident at values below 17U/ml (RR: 2.01, 95% Cl: 1.11-3.67, p=0.022), which was not the case among women. Furthermore, values below 17 U/ml were also associated with ischemic stroke (RR = 3.67, 95% Cl: 1.34-10.1, p=0.01), but not with CHD. Conclusion: Low IgM anti-PC could be a novel risk marker for development of ischemic stroke in men. Further studies are needed to establish gender and subgroup differences. (C) 2008 Elsevier Ireland Ltd. All rights reserved