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

Research output: Contribution to journalArticlepeer-review


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
JournalCardiovascular Research
Early online date8 Mar 2023
Publication statusE-pub ahead of print - 8 Mar 2023


  • beta 1
  • beta 2
  • beta 3
  • M2
  • immune system
  • autoimmunity


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