학술논문

Remodeling of the HDL proteome with treatment response to abatacept or adalimumab in the AMPLE trial of patients with rheumatoid arthritis
Document Type
article
Source
Subject
Biomedical and Clinical Sciences
Clinical Sciences
Atherosclerosis
Autoimmune Disease
Arthritis
Rheumatoid Arthritis
Clinical Research
Aetiology
2.1 Biological and endogenous factors
6.1 Pharmaceuticals
Evaluation of treatments and therapeutic interventions
Inflammatory and immune system
Abatacept
Adalimumab
Adult
Antirheumatic Agents
Arthritis
Rheumatoid
Biomarkers
Chromatography
High Pressure Liquid
Female
Humans
Ion Mobility Spectrometry
Lipoproteins
HDL
Male
Mass Spectrometry
Middle Aged
Proteome
Time Factors
Treatment Outcome
High density lipoproteins
Rheumatoid arthritis
Cardiorespiratory Medicine and Haematology
Cardiovascular System & Hematology
Cardiovascular medicine and haematology
Clinical sciences
Language
Abstract
Background and aimsTo evaluate changes in the high-density lipoprotein (HDL) proteome and HDL function in active rheumatoid arthritis (RA) patients initiating therapy with abatacept or adalimumab in the Abatacept Versus Adalimumab Comparison in Biologic-Naïve RA Subjects with Background Methotrexate (AMPLE) study.MethodsUltra high-pressure liquid chromatography (UHPLC) coupled with ion mobility mass spectrometry (LC-IM-MS) was used to analyze proteins associated with immunoaffinity-captured HDL from plasma of 30 patients with RA randomized to either abatacept (n = 15) or adalimumab (n = 15) therapy. Paraoxonase 1 (PON1) activity, HDL anti-oxidant capacity, cholesterol profiles, and homocysteine levels were also measured at baseline and following treatment. Repeated-measures analyses were performed using mixed-effect linear models to model the within-subject covariance over time.ResultsIn models controlling for age, sex and treatment group, improvement in inflammation measured by decreases in CRP was associated with improvement in HDL function and changes in several HDL-associated proteins including significant decreases in lipopolysaccharide-binding protein, serum amyloid A-I (SAA-I) and inter-alpha-trypsin inhibitor heavy chain H4 (p values