Association of β1-Adrenergic, M2-Muscarinic Receptor Autoantibody with Occurrence and Development of Nonvalvular Atrial Fibrillation

Atrial fibrillation (AF) is the most common sustained arrhythmia and is independently associated with increased risk of stroke and death. Although the exact mechanisms of AF are not completely elucidated, a large number of evidences demonstrate that autoimmunity may play an important role in the initiation, the progression, and the maintenance of AF. In this study, we aimed to compare anti-β1-adrenergic receptor autoantibody (anti-β1-R) and anti-M2-muscarinic receptor autoantibody (anti-M2-R) levels between nonvalvular AF patients and healthy control subjects.The levels of serum anti-β1-R, antinuclear antibodies, and anti-M2-R were measured in both groups by enzyme-linked immunosorbent assay (ELISA). High-sensitivity C-reactive protein (hs-CRP) and interleukin (IL)-6 concentration were measured, respectively, by immunoturbidimetry and chemiluminescence.Anti-β1-R and anti-M2-R levels were significantly higher in patients with nonvalvular AF than in healthy controls (anti-β1-R 221.11 [132.38-291.69] ng/mL vs 198.14 [125.70-278.40] ng/mL, P < 0.01; anti-M2-R 271.81 [144.99-378.20] ng/mL vs 235.01 [121.53-358.99] ng/mL, P < 0.01). Compared with the control group, the serum levels of IL-6 and hs-CRP were higher in the nonvalvular AF group (IL-6 19.65 ± 5.6 pg/mL vs 6.79 ± 1.09 pg/mL, hs-CRP 6.03 ± 1.35 mg/L vs 2.73 ± 0.63 mg/L, P < 0.05). Antinuclear antibody (ANA) levels were similar between two groups (ANA 10.55 [1.86-271.8] U/mL vs 10.49 [1.303-161.7] U/mL, P > 0.05). The baseline value of serum anti-β1-R (odds ratio [OR]: 13.176, P < 0.001), anti-M2-R (OR: 4.41, P < 0.001), IL-6 (OR: 6.126, P < 0.05) levels, and left atrial diameter (OR: 5.781, P < 0.05) were independent predictors of nonvalvular AF by multivariable analyses.We found a significant association between circulating serum anti-β1-R, anti-M2-R, IL-6 levels, and nonvalvular AF. We presume that the autoimmunity and inflammation might take part in electrical remodeling and structural remodeling of left atrium.