A novel inflammatory biomarker, GlycA, associates with disease activity in rheumatoid arthritis and cardio-metabolic risk in BMI-matched controls

Abstract

BackgroundRA and CVD both have inflammation as part of the underlying biology. Our objective was to explore the relationships of GlycA, a measure of glycosylated acute phase proteins, with inflammation and cardiometabolic risk in RA, and explore whether these relationships were similar to those for persons without RA.MethodsPlasma GlycA was determined for 50 individuals with mild-moderate RA disease activity and 39 controls matched for age, gender, and body mass index (BMI). Regression analyses were performed to assess relationships between GlycA and important markers of traditional inflammation and cardio-metabolic health: inflammatory cytokines, disease activity, measures of adiposity and insulin resistance.ResultsOn average, RA activity was low (DAS-28 = 3.0 ± 1.4). Traditional inflammatory markers, ESR, hsCRP, IL-1β, IL-6, IL-18 and TNF-α were greater in RA versus controls (P < 0.05 for all). GlycA concentrations were significantly elevated in RA versus controls (P = 0.036). In RA, greater GlycA associated with disease activity (DAS-28; RDAS-28 = 0.5) and inflammation (RESR = 0.7, RhsCRP = 0.7, RIL-6 = 0.3: P < 0.05 for all); in BMI-matched controls, these inflammatory associations were absent or weaker (hsCRP), but GlycA was related to IL-18 (RhsCRP = 0.3, RIL-18 = 0.4: P < 0.05). In RA, greater GlycA associated with more total abdominal adiposity and less muscle density (Rabdominal-adiposity = 0.3, Rmuscle-density = −0.3, P < 0.05 for both). In BMI-matched controls, GlycA associated with more cardio-metabolic markers: BMI, waist circumference, adiposity measures and insulin resistance (R = 0.3-0.6, P < 0.05 for all).ConclusionsGlycA provides an integrated measure of inflammation with contributions from traditional inflammatory markers and cardio-metabolic sources, dominated by inflammatory markers in persons with RA and cardio-metabolic factors in those without.

Association Between Smoking and Serum GlycA and High‐Sensitivity C‐Reactive Protein Levels: The Multi‐Ethnic Study of Atherosclerosis (MESA) and Brazilian Longitudinal Study of Adult Health (ELSA‐Brasil)

“…Atherothrombotic CVD is described as a chronic inflammatory condition, which involves processes mediated by cytokines and acute phase reactants . Indeed, higher CVD risk in chronic inflammatory conditions has been shown to be associated with higher GlycA levels . In addition, GlycA is shown to be associated with other measures of subclinical CVD.…”

GlycA Is a Novel Biomarker of Inflammation and Subclinical Cardiovascular Disease in Psoriasis

“…Strikingly, GlycA also showed associations with BMI and fitness among adolescents 30 , suggesting its role even in the early stages of cardiometabolic dysfunction. Additionally, in inflammatory states, GlycA associated with disease activity as well as CHD among rheumatoid arthritis patients 15, 18 , and was elevated in patients with SLE compared to controls 16 . Finally, GlycA also associated with disease activity in SLE, and revealed improved levels subsequent to treatment 17 .…”

“…Recent studies have demonstrated GlycA to be a strong predictor of future CV events 11, 12 , incident type 2 diabetes 13, 14 , long-term risk of severe infection 4 , and overall mortality 12 . Moreover, GlycA showed promise in the assessment of disease activity, treatment response, and CAD in patients with inflammatory disorders, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis 15–18 .…”

Cachexia induced by cancer and chemotherapy yield distinct perturbations to energy metabolism

“…It is well established that the growth of the C26 tumour leads to a significant increase in interleukin‐6 (IL‐6) levels, which correlate with the loss of body weight and lead to hepatic synthesis and secretion of acute phase proteins . In a recent study of rheumatoid arthritis, GlycA was significantly correlated with circulating IL‐6 . Some chemotherapeutics, such as cyclophosphamide‐doxorubicin‐5‐fluorouracil, can lead to increases in IL‐6 production, thus promoting changes in body composition and fatigue .…”