IMR Press / FBL / Volume 24 / Issue 6 / DOI: 10.2741/4766

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
Anti-ß1-Adrenoreceptor auto-Antibodies in elderly heart failure patients
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1 Charite, Universitatsmedizin Berlin, Campus Virchow Klinikum, Department of Internal Medicine, Cardiology, Berlin, Germany
2 German Centre for Cardiovascular Research (DZHK), Partner Site Berlin, Germany
3 Experimental and Clinical Research Center, Charite, Universitatsmedizin Berlin, Campus Buch Berlin, Germany
4 Herzzentrum Gottingen, Universitatsklinikum Gottingen, Abteilung fur Kardiologie und Pneumologie, Gottingen, Germany
5 Charite, Universitatsmedizin Berlin, Campus Charite Mitte, Department of Internal Medicine, Cardiology/Angiology, Berlin, Germany
6 Universitatsklinikum Schleswig-Holstein, Campus Lubeck, Klinik fur Rheumatologie, Lubeck, Germany
7 Charite, Universitatsmedizin Berlin, Campus Campus Virchow Klinikum, Department of Nephrology and Intensive Care, Berlin, Germany
8 HealthTwist GmbH, Biomedizinischer Forschungscampus Berlin-Buch, Germany
9 CellTrend, Biotechnologiepark, Luckenwalde, Germany
10 HELIOS Klinikum Berlin-Buch GmbH, Klinik und Poliklinik fur Kardiologie und Nephrologie, Berlin-Buch, Germany
Front. Biosci. (Landmark Ed) 2019, 24(6), 1037–1049; https://doi.org/10.2741/4766
Published: 1 March 2019
Abstract

An autoimmune reaction directed against the cardiac b1-adrenergic receptor (ß1-ADR) leading to the generation of autoantibodies (AA) against this G-coupled receptor has been described in patients with heart failure (HF). Agonist-like ß1-ADR-AA are associated with morbidity in HF patients and even predict mortality. Standardised and valid diagnostic tools to detect ß1-ADR-AA in clinical routine are lacking. We used a novel ELISA approach to investigate ß1-ADR-AA in a cohort of 574 HF patients of the CIBIS-ELD trial with follow up. The CIBIS-ELD trial compared the titration of bisoprolol and carvedilol to recommended target doses in regard to BB tolerability in patients aged 65 years and older. Patient with left ventricular (LV) ejection fraction (EF) < 50% or LV diameter end diastolic (DED) >55 cm showed significantly higher levels of ß1-ADR-AA. Although not yet fully validated, this ELISA allowed for a negative correlation of ß1-ADR-AA with the EF at baseline and at the follow up, ß1-ADR-AA further correlated positively with basal heart rate at follow up 12 weeks later. ß1-ADR-AA levels thus determined significantly increased under titration with beta-blockers (p<0.0.1). Changes in ß1-ADR-AA between F-Up and baseline were significantly higher in patients who used beta blockers (p=0.0.16) before study inclusion. The type of beta-blocker (BB) titrated in this study did not affect log ß1-ADR-AA levels at baseline (p=0.1.32), follow-up (p=0.0.58), nor the change (p=0.4.26). ß1-ADR-AA levels were estimated using a novel, commercially available ELISA. Although not yet fully validated, this ELISA allowed for pathophysiological insights: ß1-ADR-AA levels thus determined significantly increased under titration with beta-blockers (p<0.0.1), irrespective of type of BB. Higher levels of ß1-ADR-AA at baseline are associated with higher heart rates, lower ejection fraction and enlarged left ventricles. The relevance of the ß1-ADR-AA biomarker should be further evaluated.

Keywords
Heart Failure
Beta Blockers
Beta Receptors
Autoantibodies
ELISA
Figures
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