학술논문
Clinical and prognostic associations of autoantibodies recognizing adrenergic/muscarinic receptors in patients with heart failure.
Document Type
Article
Author
Markousis-Mavrogenis, George; Minich, Waldemar B; Al-Mubarak, Ali A; Anker, Stefan D; Cleland, John G F; Dickstein, Kenneth; Lang, Chim C; Ng, Leong L; Samani, Nilesh J; Zannad, Faiez; Metra, Marco; Seemann, Petra; Hoeg, Antonia; Lopez, Patricio; Veldhuisen, Dirk J van; Boer, Rudolf A de; Voors, Adriaan A; van der Meer, Peter; Schomburg, Lutz; Bomer, Nils
Source
Subject
*MUSCARINIC receptors
*HEART failure patients
*AUTOANTIBODIES
*CHRONIC obstructive pulmonary disease
*CHEMILUMINESCENCE immunoassay
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Language
ISSN
0008-6363
Abstract
Aims The importance of autoantibodies (AABs) against adrenergic/muscarinic receptors in heart failure (HF) is not well-understood. We investigated the prevalence and clinical/prognostic associations of four AABs recognizing the M2-muscarinic receptor or the β1-, β2-, or β3-adrenergic receptor in a large and well-characterized cohort of patients with HF. Methods and results Serum samples from 2256 patients with HF from the BIOSTAT-CHF cohort and 299 healthy controls were analysed using newly established chemiluminescence immunoassays. The primary outcome was a composite of all-cause mortality and HF rehospitalization at 2-year follow-up, and each outcome was also separately investigated. Collectively, 382 (16.9%) patients and 37 (12.4%) controls were seropositive for ≥1 AAB (P = 0.045). Seropositivity occurred more frequently only for anti-M2 AABs (P = 0.025). Amongst patients with HF, seropositivity was associated with the presence of comorbidities (renal disease, chronic obstructive pulmonary disease, stroke, and atrial fibrillation) and with medication use. Only anti-β1 AAB seropositivity was associated with the primary outcome [hazard ratio (95% confidence interval): 1.37 (1.04–1.81), P = 0.024] and HF rehospitalization [1.57 (1.13–2.19), P = 0.010] in univariable analyses but remained associated only with HF rehospitalization after multivariable adjustment for the BIOSTAT-CHF risk model [1.47 (1.05–2.07), P = 0.030]. Principal component analyses showed considerable overlap in B-lymphocyte activity between seropositive and seronegative patients, based on 31 circulating biomarkers related to B-lymphocyte function. Conclusions AAB seropositivity was not strongly associated with adverse outcomes in HF and was mostly related to the presence of comorbidities and medication use. Only anti-β1 AABs were independently associated with HF rehospitalization. The exact clinical value of AABs remains to be elucidated. [ABSTRACT FROM AUTHOR]