Clinical and prognostic associations of autoantibodies recognizing adrenergic/muscarinic receptors in patients with heart failure

George Markousis-Mavrogenis, Waldemar B. Minich, Ali A. Al-Mubarak, Stefan D. Anker, John G. F. Cleland, Kenneth Dickstein, Chim C. Lang, Leong L. Ng, Nilesh J. Samani, Faiez Zannad, Marco Metra, Petra Seemann, Antonia Hoeg, Patricio Lopez, Dirk J. van Veldhuisen, Rudolf A. de Boer, Adriaan A. Voors, Peter van der Meer, Lutz Schomburg (Lead / Corresponding author), Nils Bomer

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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 analyzed 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, 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.

Original languageEnglish
Article numbercvad042
Pages (from-to)1690–1705
Number of pages16
JournalCardiovascular Research
Volume119
Issue number8
Early online date8 Mar 2023
DOIs
Publication statusPublished - Jun 2023

Keywords

  • Autoimmunity
  • Beta 1
  • Beta 2
  • Beta 3
  • Immune system
  • M2

ASJC Scopus subject areas

  • General Medicine

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