Real world utilization of the myositis autoantibody panel.

OBJECTIVE: Myositis autoantibody panel results can offer diagnostic and prognostic information in patients with concern for idiopathic inflammatory myopathy (IIM). However, there has been widespread utilization of myositis autoantibody testing clinically, often in situations where concern for an IIM is unclear. We sought to determine ordering practices and factors predicting positive results on ordered myositis antibody panels. METHODS: We included all patients in the Duke University Health System who had a "myositis antibody panel" ordered from October 2014 through December 2016. Retrospective chart review was performed evaluating antibody positivity, provider specialty, ordering location, demographics, medical history, review of systems (ROS), physical examination (PE), and laboratory values. Fisher's exact and t test tests and backward multivariable regression analysis were performed for statistical analysis. RESULTS: There were 642 unique tests obtained with 114 positive autoantibodies (17.7%) over the 26-month period. Myositis-specific autoantibodies (MSAs) were the most common and anti-Mi-2 was the most frequent (40% of MSAs). Pulmonology providers ordered the majority of tests (383; 59.6%). Adult Rheumatology had the highest antibody positivity rate (34.3%, p=0.0001) among specialties with at least 10 panels ordered. In backward multivariable regression analysis, factors independently associated with a positive myositis antibody panel were chronic corticosteroid use (OR: 2.10, 95% CI: 1.30-3.38) and sclerodermoid skin changes (OR: 6.89; 95% CI: 2.02-23.47). CONCLUSION: The positivity rate of myositis antibody panel testing in this real-world clinical setting was 18%. Anti-Mi-2 antibody was the most frequent autoantibody present. Specific factors associated with positive results can be utilized to identify patients at higher risk for IIM. KEY POINTS: • Only eighteen percent of all myositis antibody panel tests ordered returned positive. • Anti-Mi-2 antibody was the most frequent autoantibody in our cohort. • Specific factors associated with positive results can help identify patients at higher risk for IIM, particularly for non-rheumatologists.

Rheumatoid arthritis complicates noninvasive whole blood gene expression testing for coronary artery disease.

BACKGROUND: Our objective was to evaluate an age- and sex-specific gene expression score (ASGES) previously validated to detect obstructive coronary artery disease (CAD) in patients with rheumatoid arthritis (RA). METHODS: We evaluated 20 pairs of nondiabetic coronary patients with and without RA, selected by matching on age, sex, race, body mass index, tobacco use, and number of diseased coronary vessels. Peripheral blood gene expression levels of 23 CAD-associated genes were measured, and a previously validated CAD risk score including age, sex, and gene expression levels (Corus CAD) was computed. Linear regression was used to determine effects of both CAD and RA on the ASGES. RESULTS: Among patients with RA, the ASGES was not associated with CAD. The ASGES was elevated in patients with RA (P<.04) when compared with matched controls. The presence of RA was associated with significantly altered expression for 6 of the 23 genes (P<.05 for all, not adjusted for multiple comparisons): S100 calcium binding protein A12, interleukin-18 receptor accessory protein, caspase 5, S100 calcium binding protein A8, aquaporin 9, and cluster of differentiation 79b. CONCLUSIONS: Across a range of coronary artery disease severity, RA was associated with altered expression of CAD-associated genes. Notably, 2 of these genes, S100 calcium binding protein A8 and A12, are associated with neutrophil activation and are under investigation as therapeutic targets for both RA and CAD. These findings highlight common pathogenic mechanisms for RA and CAD and validate the prior exclusion of RA patients from ASGES-based evaluation of CAD likelihood.

Molecular alterations in skeletal muscle in rheumatoid arthritis are related to disease activity, physical inactivity, and disability.

BACKGROUND: To identify molecular alterations in skeletal muscle in rheumatoid arthritis (RA) that may contribute to ongoing disability in RA. METHODS: Persons with seropositive or erosive RA (n = 51) and control subjects matched for age, gender, race, body mass index (BMI), and physical activity (n = 51) underwent assessment of disease activity, disability, pain, physical activity and thigh muscle biopsies. Muscle tissue was used for measurement of pro-inflammatory markers, transcriptomics, and comprehensive profiling of metabolic intermediates. Groups were compared using mixed models. Bivariate associations were assessed with Spearman correlation. RESULTS: Compared to controls, patients with RA had 75% greater muscle concentrations of IL-6 protein (p = 0.006). In patients with RA, muscle concentrations of inflammatory markers were positively associated (p < 0.05 for all) with disease activity (IL-1ß, IL-8), disability (IL-1ß, IL-6), pain (IL-1ß, TNF-α, toll-like receptor (TLR)-4), and physical inactivity (IL-1ß, IL-6). Muscle cytokines were not related to corresponding systemic cytokines. Prominent among the gene sets differentially expressed in muscles in RA versus controls were those involved in skeletal muscle repair processes and glycolytic metabolism. Metabolic profiling revealed 46% higher concentrations of pyruvate in muscle in RA (p < 0.05), and strong positive correlation between levels of amino acids involved in fibrosis (arginine, ornithine, proline, and glycine) and disability (p < 0.05). CONCLUSION: RA is accompanied by broad-ranging molecular alterations in skeletal muscle. Analysis of inflammatory markers, gene expression, and metabolic intermediates linked disease-related disruptions in muscle inflammatory signaling, remodeling, and metabolic programming to physical inactivity and disability. Thus, skeletal muscle dysfunction might contribute to a viscous cycle of RA disease activity, physical inactivity, and disability.

A Novel Protein Glycan-Derived Inflammation Biomarker Independently Predicts Cardiovascular Disease and Modifies the Association of HDL Subclasses with Mortality.

BACKGROUND: Evidence suggests that systemic inflammation may adversely impact HDL function. In this study we sought to evaluate the independent and incremental predictive performance of GlycA-a novel serum inflammatory biomarker that is an aggregate measure of enzymatically glycosylated acute phase proteins-and HDL subclasses on adverse events in a retrospective observational study of a secondary prevention population and to understand a priori defined potential interactions between GlycA and HDL subclasses. METHODS: GlycA and HDL subclasses were measured using proton nuclear magnetic resonance spectroscopy in 7617 individuals in the CATHGEN (CATHeterization GENetics) cardiac catheterization biorepository. RESULTS: GlycA was associated with presence [odds ratio (OR) 1.07 (1.02-1.13), P = 0.01] and extent [OR 1.08 (1.03, 1.12) P < 0.0005] of coronary artery disease and with all-cause mortality [hazard ratio (HR) 1.34 (1.29-1.39), P < 0.0001], cardiovascular mortality [1.37 (1.30-1.45), P < 0.0001] and noncardiovascular mortality [1.46 (1.39-1.54) P < 0.0001] in models adjusted for 10 cardiovascular risk factors. GlycA and smaller HDL subclasses had independent but opposite effects on mortality risk prediction, with smaller HDL subclasses being protective [HR 0.69 (0.66-0.72), P < 0.0001]. There was an interaction between GlycA and smaller HDL subclasses-increasing GlycA concentrations attenuated the inverse association of smaller HDL subclasses with mortality. Adding GlycA and smaller HDL subclasses into the GRACE (Global Registry of Acute Coronary Events) and Framingham Heart Study Risk Scores improved mortality risk prediction, discrimination and reclassification. CONCLUSIONS: These findings highlight the interaction of systemic inflammation and HDL with clinical outcomes and may increase precision for clinical risk assessment in secondary prevention populations.

Heart failure as a risk factor for osteoporosis and fractures.

Although heart failure (HF) and osteoporosis are common diseases, particularly in elderly populations, patients with HF have an increased risk for osteoporosis. The relationship of HF with osteoporosis is modified by gender and the severity of HF. In addition, shared risk factors, medication use, and common pathogenic mechanisms affect both HF and osteoporosis. Shared risk factors for these 2 conditions include advanced age, hypovitaminosis D, renal disease, and diabetes mellitus. Medications used to treat HF, including spironolactone, thiazide diuretics, nitric oxide donors, and aspirin, may protect against osteoporosis. In contrast, loop diuretics may make osteoporosis worse. HF and osteoporosis appear to share common pathogenic mechanisms, including activation of the renin-angiotensin-aldosterone system, increased parathyroid hormone levels, and/or oxidative/nitrosative stress. HF is a major risk factor for mortality following fractures. Thus, in HF patients, it is important to carefully assess osteoporosis and take measures to reduce the risk of osteoporotic fractures.