Analysis of the common genetic component of large-vessel vasculitides through a meta- Immunochip strategy

Giant cell arteritis (GCA) and Takayasu's arteritis (TAK) are major forms of large-vessel vasculitis (LVV) that share clinical features. To evaluate their genetic similarities, we analysed Immunochip genotyping data from 1,434 LVV patients and 3,814 unaffected controls. Genetic pleiotropy was also estimated. The HLA region harboured the main disease-specific associations. GCA was mostly associated with class II genes (HLA-DRB1/HLA-DQA1) whereas TAK was mostly associated with class I genes (HLA-B/MICA). Both the statistical significance and effect size of the HLA signals were considerably reduced in the cross-disease meta-analysis in comparison with the analysis of GCA and TAK separately. Consequently, no significant genetic correlation between these two diseases was observed when HLA variants were tested. Outside the HLA region, only one polymorphism located nearby the IL12B gene surpassed the study-wide significance threshold in the meta-analysis of the discovery datasets (rs755374, P?=?7.54E-07; ORGCA?=?1.19, ORTAK?=?1.50). This marker was confirmed as novel GCA risk factor using four additional cohorts (PGCA?=?5.52E-04, ORGCA?=?1.16). Taken together, our results provide evidence of strong genetic differences between GCA and TAK in the HLA. Outside this region, common susceptibility factors were suggested, especially within the IL12B locus

Right ventricular and atrial functions in systemic sclerosis patients without pulmonary hypertension Speckle-tracking echocardiographic study

Background. Systemic sclerosis (SSc) is a systemic connective tissue disease and cardiac involvement is one of the most important causes of death. Right ventricular (RV) systolic dysfunction is a poor prognostic finding in SSc patients. Assessment of RV function has some difficulties because of its crescent shape and extensive trabeculations. Two-dimensional (2D) speckle-tracking echocardiography (STE) is an angle-independent quantitative technique to evaluate myocardial function. The aim of this study was to assess the RV and right atrial (RA) functions of SSc patients without pulmonary hypertension by using 2D STE. Patients and methods. A total of 40 patients with SSc (mean age 48.5 +/- 11.4 years, 28 female) and 40 healthy volunteers (mean age 45.9 +/- 7.6 years, 21 female) were included in the study. All subjects underwent transthoracic echocardiography for evaluation of RV and RA functions with 2D STE. Results. Although left ventricular systolic and diastolic functions, systolic pulmonary artery pressure (PAP), and RA measurements were similar in both groups, tricuspid annular plane systolic excursion (TAPSE) and maximum systolic myocardial velocity (S') were decreased in SSc patients. The RV free wall global longitudinal strain (GLS) of SSc patients was lower than the controls (-18.5 +/- 4.9% vs. -21.8 +/- 2.4%, p< 0.001) and the RA reservoir and conduit functions were also decreased in SSc patients compared with controls (34.4 +/- 9.9% vs. 39.7 +/- 11.2%, p= 0.027 and 15.0 +/- 5.7% vs. 18.7 +/- 6.4%, p= 0.009, respectively). Disease duration was inversely correlated with RVGLS and TAPSE (r: -0.416, p= 0.018 and r: -0.383, p= 0.031, respectively). Conclusion. The use of 2D STE can be helpful in the detection of impairment in RV and RA functions in SSc patients with normal PAP

The 2013 ACC/AHA 10-year atherosclerotic cardiovascular disease risk index is better than SCORE and QRisk II in rheumatoid arthritis: is it enough?

Objective. To determine the ability of the new American College of Cardiology and American Heart Association (ACC/AHA) 10-year atherosclerotic cardiovascular disease (ASCVD) risk algorithm in detecting high cardiovascular (CV) risk, RA patients identified by carotid ultrasonography (US) were compared with Systematic Coronary Risk Evaluation (SCORE) and QRisk II algorithms. Methods. SCORE, QRisk II, 2013 ACC/AHA 10-year ASCVD risk and EULAR recommended modified versions were calculated in 216 RA patients. In sonographic evaluation, carotid intima-media thickness >0.90 mm and/or carotid plaques were used as the gold standard test for subclinical atherosclerosis and high CV risk (US+). Results. Eleven (5.1%), 15 (6.9%) and 44 (20.4%) patients were defined as having high CV risk according to SCORE, QRisk II and ACC/AHA 10-year ASCVD risk, respectively. Fifty-two (24.1%) patients were US+ and of those, 8 (15.4%), 7 (13.5%) and 23 (44.2%) patients were classified as high CV risk according to SCORE, QRisk II and ACC/AHA 10-year ASCVD risk, respectively. The ACC/AHA 10-year ASCVD risk index better identified US+ patients than SCORE and QRisk II (P < 0.0001). With EULAR modification, reclassification from moderate to high risk occurred only in two, five and seven patients according to SCORE, QRisk II and ACC/AHA 10-year ASCVD risk, respectively. Conclusion. The 2013 ACC/AHA 10-year ASCVD risk estimator was better than the SCORE and QRisk II indices in RA, but still failed to identify 55% of high risk patients. Furthermore adjustment of threshold and EULAR modification did not work well

Subclinical Atherosclerosis in Systemic Sclerosis: Not Less Frequent Than Rheumatoid Arthritis and Not Detected With Cardiovascular Risk Indices

Objective. To determine the frequency of subclinical atherosclerosis in patients with systemic sclerosis (SSc; scleroderma) compared to healthy subjects (HS) and rheumatoid arthritis (RA) patients and to determine the ability of cardiovascular (CV) risk indices in detecting SSc patients with subclinical atherosclerosis. Methods. A total of 110 SSc patients (102 females and 8 males, mean +/- SD age 50.5 +/- 11.9 years), 110 age-and sex-matched RA patients, and 51 HS without CV disease were examined with ultrasonography (US). Carotid intima-media thickness (cIMT) >0.90 mm and/or carotid plaques were used as the gold standard for subclinical atherosclerosis (US+). Systematic Coronary Risk Evaluation (SCORE), QRisk II, and 2013 American College of Cardiology (ACC)/American Heart Association (AHA) CV risk indices were calculated. Results. Twenty-one (19.1%) SSc patients, 24 (21.8%) RA patients, and 3 (5.9%) HS had subclinical atherosclerosis (SSc versus RA: P=0.62, SSc versus HS: P=0.029). cIMT in SSc was higher compared to HS (0.68 +/- 0.15 mm versus 0.61 +/- 0.10 mm; P=0.008) but similar to RA patients (0.66 +/- 0.14 mm; P=0.82). Subclinical atherosclerosis in SSc was associated with age (odds ratio [OR] 1.07, P=0.013), elevated erythrocyte sedimentation rate (OR 3.4, P=0.045), and pulmonary arterial hypertension (OR 4.27, P=0.012). Concerning CV risk indices, of the 21 US+ SSc patients only 0, 3 (14.2%), and 6 (28.6%) were classified as high CV risk according to SCORE, QRisk II, and ACC/AHA risk indices, respectively. Conclusion. Subclinical atherosclerosis in SSc patients is more frequent than in HS, but is as frequent as in RA patients in which accelerated atherosclerosis is clearly defined. CV risk indices for the general population are considerably insufficient to detect SSc patients with atherosclerosis

Anti-CCP antibodies in rheumatoid arthritis and psoriatic arthritis

Our aim is to assess the prevalence and associated clinical features of anti-CCP (cyclic citrullinated peptide) antibodies for RF (rheumatoid factor)-positive and RF-negative rheumatoid arthritis (RA) and psoriatic arthritis (PsA). In a prospective, cross-sectional, multi-centre study, we determined the titres of anti-CCP antibodies in 208 RA patients (129 RF-positive, 79 RF-negative), 56 PsA patients and 39 healthy controls (HC). Clinical parameters including disease activity (disease activity score 28-DAS28), physical disability (health assessment questionnaire-HAQ), functional capacity (functional class) and radiological erosions were investigated in patients with RA. In PsA patients, clinical and radiological features were determined. Anti-CCP2 antibodies were measured using a second-generation anti-CCP enzyme-linked immunosorbent assay (Euro-Diagnostica, Netherlands). One-hundred four of 129 RF-positive RA (81%), 16 of 79 RF-negative RA (20%), seven of 56 PsA patients (12.5%) and none of the HC had anti-CCP antibodies. RA patients with anti-CCP antibodies had significantly higher disease activity, greater loss of function and more frequent erosive disease than anti-CCP antibody-negative group. In subgroup analysis, anti-CCP antibodies in RF-negative patients were also associated with erosive disease. All PsA patients with anti-CCP antibodies had symmetric arthritis with higher number of swollen joints. The prevalence of anti-CCP antibodies in RF-positive RA patients was significantly higher than in RF-negative RA and PsA patients. Anti-CCP antibodies were also associated with erosive disease in RF-negative RA patients. Both anti-CCP and RF tests were negative in 30% of the patients. Anti-CCP positivity was a frequent finding in PsA and associated with symmetrical polyarthritis

Faith in Trump, Moral Foundations, and Social Distancing Defiance during the Coronavirus Pandemic

Purpose: Over the past several months, the coronavirus has infected more than six million Americans and killed nearly 200,000. Governors have issued stay-at-home orders, and prosecutors have filed criminal charges against individuals for defying those orders. And yet many Americans have still refused to keep their distance from their fellow citizens, even if they had symptoms of infection. The authors explore the underlying causes for those who intend to defy these norms. Methods: Using national-level data from a March 2020 survey of 989 Americans, the authors explore intentions to defy social distancing norms by testing an interactionist theory of foundation-based moral behavior in combination with faith in President Trump during the coronavirus pandemic. The analysis controls for a range of variables, including measures of low self-control and deterrence. Results: Low self-control is the strongest predictor of defiance intentions. Consistent with interactionist theory, defiance intentions are significantly higher for those holding specific faith in Trump and those endorsing binding foundations. Furthermore, the interaction of these two variables is significant and in the predicted direction. The results hold for two different measures of faith in Trump. Conclusions: Even with a strong effect for low self-control, faith in President Trump is a strong predictor of refusal to social-distance, and its effect is largest among individuals high in binding foundations

Race and Worrying About Police Brutality: The Hidden Injuries of Minority Status in America

Given the historically contentious relationship – including most notably the use of excessive and lethal force – between the police and African Americans, the current project examines the extent to which Blacks in the United States fear police brutality. The study is based on a national-level survey (N = 1,000), and measures fear by how much respondents “worry” about experiencing police force. The data support the racial divide hypothesis, showing that Blacks’ worry about such violence is over five times that of Whites. Guided by the racial/ethnic gradient hypothesis, the analyses also assess Hispanic respondents’ level of worry. Rather than forming a gradient by falling midway between Blacks and Whites, Hispanics’ worry about police brutality more closely reflects those of Blacks at more than four times that of Whites, suggesting a racial/ethnic divide. These findings thus assert that worrying about police brutality is an emotional injury that minorities disproportionately experience and whose pervasiveness remains largely hidden from view

Faith in Trump, Moral Foundations, and Social Distancing Defiance during the Coronavirus Pandemic

Purpose: Over the past several months, the coronavirus has infected more than six million Americans and killed nearly 200,000. Governors have issued stay-at-home orders, and prosecutors have filed criminal charges against individuals for defying those orders. And yet many Americans have still refused to keep their distance from their fellow citizens, even if they had symptoms of infection. The authors explore the underlying causes for those who intend to defy these norms. Methods: Using national-level data from a March 2020 survey of 989 Americans, the authors explore intentions to defy social distancing norms by testing an interactionist theory of foundation-based moral behavior in combination with faith in President Trump during the coronavirus pandemic. The analysis controls for a range of variables, including measures of low self-control and deterrence. Results: Low self-control is the strongest predictor of defiance intentions. Consistent with interactionist theory, defiance intentions are significantly higher for those holding specific faith in Trump and those endorsing binding foundations. Furthermore, the interaction of these two variables is significant and in the predicted direction. The results hold for two different measures of faith in Trump. Conclusions: Even with a strong effect for low self-control, faith in President Trump is a strong predictor of refusal to social-distance, and its effect is largest among individuals high in binding foundations